MicroRNAs as Regulators of Phagocytosis

May combine two claims.

Prostaglandin E2 inhibits miR-21a, responsible for regulation STAT3, thus preventing the switch from M1 to M2 macrophages.

“The pro-inflammatory phenotype is also induced by prostaglandin E2 (PGE2) which inhibits miR-21a, responsible for regulation STAT3, thus preventing the switch from M1 to M2 macrophages [118].”

• cites [118] Wang, Z., Brandt, S., Medeiros, A., Wang, S., Wu, H., Dent, A., and Serezani, C.H. (2015). MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E2-mediated M2 generation. PLoS ONE, 10. sourceDisputed

  The Results section (‘miR-21 is an endogenous brake in PGE2-mediated M2 polarization’; page unavailable) reports that PGE2 decreases M1 markers and increases M2 markers. The Discussion confirms that PGE2 inhibits miR-21 expression, but says this enhances—not prevents—M2 polarization. The claim reverses the paper’s central finding. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

In a mouse model, knock-out of miR-146a led to colitis, which could be ameliorated upon administration of miR-146a mimic.

“In a mouse model, knock-out of miR-146a led to colitis, which could be ameliorated upon administration of miR-146a mimic [151].”

• cites [151] Peng, 2016, Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5, EBioMedicine sourceDisputed

  The Results sections on miR-146b deficiency and mimic treatment report intestinal inflammation in miR-146b-knockout mice, but test the miR-146b mimic for colitis in IL-10-knockout mice. The paper identifies miR-146b, not miR-146a, throughout these findings; it does not report treating miR-146a-knockout mice with a miR-146a mimic. Page numbers were not available in our copy. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

miR-125b-5p, miR-143-3p, and miR-145-5p promote the pro-inflammatory phenotype; total RNA sequencing proved activation of proteins and genes responsible for pro-inflammatory cytokine synthesis and reactive oxygen species production.

“Huleihel et al. pointed out miR-125b-5p, miR-143-3p, and miR-145-5p as other factors promoting the pro-inflammatory phenotype. Based on total RNA sequencing, they proved activation of a number of proteins and genes responsible for pro-inflammatory cytokine synthesis, and reactive oxygen species production [140].”

• cites [140] Huleihel, 2017, Matrix-Bound Nanovesicles Recapitulate Extracellular Matrix Effects on Macrophage Phenotype, Tissue Eng. Part A sourceDisputed

  The Discussion reports the opposite of the claimed pro-inflammatory effect for miR-143-3p and miR-145-5p: inhibiting them increased an M1-like marker, and the authors conclude that miR-145-5p contributes to downregulation of the inflammatory phenotype. It describes miR-125b-5p as context-dependent. The RNA sequencing and data analysis section describes sequencing small RNAs to identify miRNAs, not proving activation of cytokine- or reactive-oxygen-species-producing genes and proteins. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

miR-328 augments phagocytosis and ROS production in Haemophilus influenzae infection.

“miR-328 is a key element of the host response to Haemophilus influenzae infection as it augments phagocytosis and production of ROS [173].”

• cites [173] Tay, H.L., Kaiko, G.E., Plank, M., Li, J., Maltby, S., Essilfie, A.T., Jarnicki, A., Yang, M., Mattes, J., and Hansbro, P.M. (2015). Antagonism of miR-328 increases the antimicrobial function of macrophages and neutrophils and rapid clearance of non-typeable Haemophilus influenzae (NTHi) from infected lung. PLoS Pathog., 11. sourceDisputed

  The Results report that inhibiting miR-328 increased NTHi phagocytosis and ROS production—the opposite of the claim that miR-328 itself augments them. One sentence in the Discussion says miR-328 acts 'by augmenting' these functions, but it conflicts with the reported experiments and the Discussion’s account of inhibition enhancing bacterial clearance. The indexed copy provides section labels but no page numbers. (LLM, conf=0.84)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Most human genes are targeted by microRNAs.

“Most human genes are targeted by microRNAs [5].”

• cites [5] Friedman, 2009, Most mammalian mRNAs are conserved targets of microRNAs, Genome Res. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

miR-155 drives cell differentiation.

“In addition to its function in immunity, miR-155 drives cell differentiation [59].”

• cites [59] Rao, 2008, Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder, J. Exp. Med. sourcePartly supported

  The Results report that enforced miR-155 expression in hematopoietic stem cells increased granulocyte/monocyte cells while reducing B cells and erythroid precursors. The Discussion links miR-155 to hematopoietic development but suggests that sustained expression may prevent those myeloid cells from completing their developmental programs. Thus the paper supports an effect on cell development, not the unqualified claim that miR-155 drives cell differentiation. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

Downregulation of miR-22 may appear in acute myeloid leukemia and block differentiation of bone marrow blasts; restoration of its expression relieves the block.

“Downregulation of miR-22 may appear in acute myeloid leukemia and block differentiation of bone marrow blasts; restoration of its expression relieves the block.”

• cites [185] Shen, C., Chen, M.T., Zhang, X.H., Yin, X.L., Ning, H.M., Su, R., Lin, H.S., Song, L., Wang, F., and Ma, Y.N. (2016). The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia. PLoS Genet., 12. sourceSupported

May combine two claims.

miR-22 expression is upregulated by PU.1, targets MECOM (EVI1), which further increases c-Jun but decreases GATA2 expression.

“It was demonstrated that miR-22, whose expression is upregulated by PU.1 transcription factor, targets MECOM (EVI1), which further increases c-Jun but decreases GATA2 expression.”

• cites [185] Shen, C., Chen, M.T., Zhang, X.H., Yin, X.L., Ning, H.M., Su, R., Lin, H.S., Song, L., Wang, F., and Ma, Y.N. (2016). The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia. PLoS Genet., 12. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

miR-155 is repressed by IL-10 signaling through STAT3.

“Interestingly, miR-155 is also repressed by IL-10 signaling through STAT3 [57].”

• cites [57] Androulidaki, 2009, The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs, Immunity sourceCould not verify

  The Discussion reports that Akt1 negatively regulates miR-155 in LPS-activated macrophages. The Introduction mentions STAT signalling only in connection with SOCS1, a target of miR-155. Neither passage addresses whether IL-10 represses miR-155 through STAT3; searches for IL-10, STAT3 and that regulatory pathway found no supporting passage in our copy. (LLM, conf=0.75)

  Experimental — accuracy not yet measured

May combine two claims.

miR-146a is induced by NF-κB and negatively regulates TLR signaling by targeting TRAF6 and IRAK1.

“miR-146a is also induced by NF-κB and negatively regulates TLR signaling by targeting TRAF6 and IRAK1 [58].”

• cites [58] Taganov, 2006, NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses, Proc. Natl. Acad. Sci. USA sourcePartly supported

  The Results show that LPS induction of the miR-146a promoter depends on NF-κB and that miR-146a represses reporters bearing IRAK1 and TRAF6 3′ UTRs. The Abstract and Discussion propose negative feedback on TLR signaling through these targets, but do not establish that miR-146a directly reduces TLR signaling; the claim states that proposed function as fact. Page numbers are not available in the supplied passages. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In animals, microRNA binding to a 3'UTR depends on 6-8 nucleotides at the 5' end (seed region) and typically leads to translation repression without mRNA cleavage.

“In animals, binding of a microRNA with a 3′UTR is based on 6–8 nucleotides at the 5’ end of the microRNA, called the seed region. Such an interaction typically leads to translation repression without mRNA cleavage [7].”

• cites [7] Ellwanger, 2011, The sufficient minimal set of miRNA seed types, Bioinformatics sourcePartly supported

  The Introduction (page unavailable) describes the seed as a 6–8-nucleotide sequence near the miRNA’s 5′ end, and the Results discuss seed matches in 3′UTRs. The paper mentions regulation of translation and mRNA decay, but does not establish that these interactions typically repress translation without mRNA cleavage. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

Graff et al. found increases of miR-125a-3p, miR-155-5p, miR-155-3p in M1, miR-193b in M2a, miR-27a-5p, miR-155-5p, miR-155-3p in M2b and decreases of miR-26a-2-3p and miR-29b-1-5p in both M1 and M2a.

“They noticed increases of miR-125a-3p, miR-155-5p, miR-155-3p in M1, miR-193b in M2a, miR-27a-5p, miR-155-5p, miR-155-3p in M2b and decreases of miR-26a-2-3p, and miR-29b-1-5p in both M1 and M2a.”

• cites [195] Graff, 2012, Identifying functional microRNAs in macrophages with polarized phenotypes, J. Biol. Chem. sourcePartly supported

  The Results report increased miR-125a-3p in M1, miR-193b in M2a, and miR-27a* in M2b; they also report miR-155* induction in M1 and M2b. But the Results place co-regulation of miR-26a-2* and miR-29b-1* in M1 and M2b, not M1 and M2a as claimed. The paper also cautions that most corresponding guide-strand changes in macrophages did not reach statistical significance. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

A single microRNA may target different genes involved in a single biological process, potentially leading to significant changes in cell function.

“What is more, a single microRNA may target different genes involved in a single biological process [11], potentially leading to significant changes in cell function.”

• cites [11] Loeb, 2012, Transcriptome-wide miR-155 binding map reveals widespread noncanonical microRNA targeting, Mol. Cell sourceSupported

May combine two claims.

miR-26a regulates the CREB-C/EBPβ signaling axis, and its downregulation in Mycobacterium tuberculosis infection favors M2 polarization.

“MiR-26a also regulates the CREB-C/EBPβ signaling axis, and its downregulation in Mycobacterium tuberculosis (Mtb) infection favors M2 polarization [126].”

• cites [126] Sahu, S.K., Kumar, M., Chakraborty, S., Banerjee, S.K., Kumar, R., Gupta, P., Jana, K., Gupta, U.D., Ghosh, Z., and Kundu, M. (2017). MicroRNA 26a (miR-26a)/KLF4 and CREB-C/EBPβ regulate innate immune signaling, the polarization of macrophages and the trafficking of Mycobacterium tuberculosis to lysosomes during infection. PLoS Pathog., 13. sourcePartly supported

  The Introduction and Results report that miR-26a falls during Mtb infection and that its downregulation increases KLF4, favoring M2 polarization. They describe CREB–C/EBPβ as another pathway that favors M2 polarization, not as an axis regulated by miR-26a. Page numbers are unavailable in our copy. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

miR-146b takes part in M2 polarization, is upregulated upon IL-10 stimulation, and targets interferon regulatory factor 5 (IRF5).

“The authors confirmed that miR-146b takes part in M2 polarization and it is upregulated upon IL-10 stimulation, and targets interferon regulatory factor 5 (IRF5).”

• cites [151] Peng, 2016, Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5, EBioMedicine sourcePartly supported

  The Results section, “miR-146b Induced by IL-10 Suppresses M1 Macrophage Polarization” (page unavailable), and the Discussion support IL-10-dependent miR-146b expression and its targeting of IRF5. They describe suppression of M1 polarization, not a demonstrated role in M2 polarization. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

Silencing of miR-146a-5p resulted in downregulation of M2 markers (YM1, FIZZ1, CCR7, Arg1, pSTAT6 and c/EBPβ) and upregulation of p-STAT1, IRF-1, AP1, TRAF6, IRAK1, which resulted in an increase in IL-12 and TNFα production.

“They showed that silencing of miR-146a-5p resulted in downregulation of M2 markers (YM1, FIZZ1, CCR7, Arg1, pSTAT6 and c/EBPβ) and upregulation of p-STAT1, IRF-1, AP1, TRAF6, IRAK1, which resulted in an increase in IL-12 and TNFα production [153].”

• cites [153] Das, S., Mukherjee, S., and Ali, N. (2021). Super enhancer-mediated transcription of miR146a-5p drives M2 polarization during Leishmania donovani infection. PLoS Pathog., 17. sourceSupported

May combine two claims.

miR-511 binds the 3′UTR of TLR4 and upregulates TLR4 in dendritic cells.

“They also confirmed binding of miR-511 with 3′UTR of TLR4, however, resulting in upregulation of TLR4 in dendritic cells [135].”

• cites [135] Tserel, 2011, MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4, J. Biol. Chem. sourcePartly supported

  The results section (page unavailable) reports that TLR4 protein was about twice as high in control-treated differentiating dendritic cells as in cells treated with a miR-511 inhibitor, supporting positive regulation. It identifies predicted miR-511 sites in the TLR4 3′UTR and tests those fragments in luciferase reporters, but does not confirm direct binding. The paper describes miR-511 as a putative regulator, so the citing sentence overstates that part of the evidence. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

let-7c expression is suppressed by LPS, whereas its upregulation results in a change from the M1 to M2 phenotype by targeting the C/EBP-δ transcription factor.

“Expression of let-7c is suppressed by LPS, whereas its upregulation results in a change from the M1 to M2 phenotype by targeting the C/EBP-δ transcription factor [110].”

• cites [110] Banerjee, 2013, MicroRNA let-7c regulates macrophage polarization, J. Immunol. sourceSupported

May combine two claims.

IL-4 and IL-13 activate PPARγ, which in turn activates transcription of miR-223, another marker of M2 polarization.

“IL-4 and IL-13 activates PPARγ, which in turn activates transcription of miR-223—another marker of M2 polarization [197].”

• cites [197] Ying, 2015, MicroRNA-223 is a crucial mediator of PPARγ-regulated alternative macrophage activation, J. Clin. Investig. sourcePartly supported

  The Introduction and the section on PPARγ regulation of miR-223 report that PPARγ directly promotes miR-223 expression; the results also show miR-223 induction in IL-4-stimulated M2 macrophages. The cited paper does not establish the full stated sequence in which both IL-4 and IL-13 activate PPARγ: the passages address IL-4, but not IL-13, and do not directly show IL-4 activating PPARγ. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

miR-24 is a negative regulator of macrophage classical activation induced by LPS; its mechanism involves modulation of phosphoinositide 3-kinase (PI3K) and further inhibition of cytokine synthesis.

“MiR-24 is an example of a negative regulator of macrophage classical activation induced by LPS. The identified mechanism of action involves modulation of phosphoinositide 3-kinase (PI3K) and further inhibition of cytokine synthesis [124].”

• cites [124] Fordham, 2015, miR-24 Regulates Macrophage Polarization and Plasticity, J. Clin. Cell. Immunol. sourcePartly supported

  The Introduction and Abstract Conclusion identify miR-24 as a negative regulator of LPS-induced classical macrophage activation, and the Abstract Results report inhibited cytokine secretion and reduced expression of the PI3K subunit p110δ. But the Abstract Conclusion says p110δ involvement in cytokine inhibition “may” explain the effect; the Discussion also presents it as a possibility, not an identified mechanism. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Among PRRs, TLRs play a crucial role in the inflammatory responses to pathogenic infection and have been a target for many studies exploring phagocytosis.

“Among the mentioned PRRs, TLRs play crucial role in the inflammatory responses to pathogenic infection and have been a target for many studies exploring phagocytosis course [201,202,203].”

• cites [201] Yang, 2020, TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer’s Disease, Front. Immunol. sourceSupported
• cites [202] Takeda, 2005, Toll-like receptors in innate immunity, Int. Immunol. sourceNot checked — no full text of the source
• cites [203] Lee, 2019, TLR4 (toll-like receptor 4) activation suppresses autophagy through inhibition of FOXO3 and impairs phagocytic capacity of microglia, Autophagy sourceSupported

May combine two claims.

miR-1, miR-99b, miR-139-5p, miR-212, miR-218, and miR-511 are overexpressed in macrophages and involved in the TLR signaling pathway.

“Tserel et al. identified miR-1, miR-99b, miR-139-5p, miR-212, miR-218, and miR-511 as overexpressed in macrophages and involved in the toll-like receptor signaling pathway”

• cites [135] Tserel, 2011, MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4, J. Biol. Chem. sourcePartly supported

  The 'Updated miRNA profile of human DCs and MFs' section reports that miR-99b, miR-212 and miR-511 were highly up-regulated in both dendritic cells and macrophages relative to monocytes, while miR-139-5p, miR-1 and miR-218 had higher expression in macrophages. Table 1 (FOOTNOTES; page unavailable) identifies predicted Toll-like receptor signaling targets for miR-511, and the Discussion examines its possible effect on TLR4. The paper does not establish that all six miRNAs are involved in that pathway. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

M1 macrophages transfected with miR-125a-5p are less potent in exerting bactericidal activity against Escherichia coli, which results from targeting Kruppel-like Factor 13 (KLF13) and promotion of M2 polarization.

“M1 macrophages, when transfected with miR-125a-5p, are less potent in exerting bactericidal activity against Escherichia coli, which results from targeting Kruppel-like Factor 13 (KLF13) and promotion of M2 polarization [138].”

• cites [138] Banerjee, 2013, miR-125a-5p regulates differential activation of macrophages and inflammation, J. Biol. Chem. sourcePartly supported

  In ‘miR-125a-5p Regulates Macrophage Activation’ (page not supplied), the paper reports that miR-125a-5p-transfected GM-BMM had diminished bactericidal activity against E. coli and that miR-125a-5p promotes M2 markers. It identifies KLF13 as a target but says the functional effects are ‘likely’ mediated by KLF13 and may not be solely mediated by it. The paper does not establish that promotion of M2 polarization causes the reduction in bacterial killing. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Overexpression of miR-340 promoted macrophages to have the M1-like phenotype; miR-340 directly regulates and inversely correlates with CD47.

“The overexpression of miR-340 promoted macrophages to have the M1-like phenotype. The authors noticed that miR-340 directly regulates and inversely correlates with CD47, the protein involved in cell migration, adhesion, and apoptosis [174].”

• cites [174] Xi, 2020, Restoration of miR-340 controls pancreatic cancer cell CD47 expression to promote macrophage phagocytosis and enhance antitumor immunity, J. Immunother. Cancer sourceSupported

May combine two claims.

CD47-SIRPα pathway activation correlates with the expression level of miR-378a; miR-378a affects phagocytosis and macrophage differentiation by targeting CD47-SIRPα.

“On the other hand, Chen et al. correlated CD47-SIRPα pathway activation with the expression level of miR-378a. The authors indicated that miR-378a affects phagocytosis and macrophage differentiation by targeting CD47-SIRPα [175].”

• cites [175] Chen, 2019, miR-378a Modulates Macrophage Phagocytosis and Differentiation through Targeting CD47-SIRPα Axis in Atherosclerosis, Scand. J. Immunol. sourcePartly supported

  The Discussion states that miR-378a modulates macrophage phagocytosis and differentiation through the CD47–SIRPα axis. Sections 2.6 and 2.8 show that changing miR-378a levels changes SIRPα expression, but they do not establish a correlation with pathway activation specifically. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

Upon Leishmania donovani infection, miR-146a-5p is upregulated in a BRD4/p300-dependent manner; miR-181a-5p and miR-125a-5p are upregulated, whereas miR-26a-5p is downregulated, which promotes M2 over M1 polarization.

“Contrary to the abovementioned NGS results, Das et al. reported that upon Leishmania donovani infection, miR-146a-5p is upregulated in a BET bromodomain protein 4 (BRD4)/p300-depdendent manner (in this conditions miR-181a-5p and miR-125a-5p are upregulated too, whereas miR-26a-5p is downregulated, which promotes M2 over M1 polarization).”

• cites [153] Das, S., Mukherjee, S., and Ali, N. (2021). Super enhancer-mediated transcription of miR146a-5p drives M2 polarization during Leishmania donovani infection. PLoS Pathog., 17. sourceSupported

May combine two claims.

These microRNAs modulate expression of TLR2, TLR4, and scavenger receptors SR-A, SR-BI, and CD36.

“They modulate expression of TLR2 and TLR4, as well as scavenger receptors (SR-A, SR-BI, CD36).”

• cites [204] Madadi, 2019, Potential microRNA-related targets in clearance pathways of amyloid-β: Novel therapeutic approach for the treatment of Alzheimer’s disease, Cell Biosci. sourceSupported

May combine two claims.

miR-21 knockout increases bacterial burden, and this effect may be reversed by synthetic miR-21.

“Knock-out of miR-21 results in an increased bacterial burden, and this effect may be reversed by synthetic miR-21.”

• cites [119] Johnston, 2017, MicroRNA-21 Limits Uptake of Listeria monocytogenes by Macrophages to Reduce the Intracellular Niche and Control Infection, Front. Cell. Infect. Microbiol. sourceSupported

May combine two claims.

In a viral infection model, miR-155 is induced via a TLR/MyD88-independent, RIG-I/JNK/NF-κB-dependent pathway, downregulating SOCS1 and enhancing type I IFN signaling, potentially exacerbating inflammation.

“It was shown that in a model of viral infection, miR-155 expression is induced in a TLR/MyD88-independent but retinoic acid-inducible gene I/JNK/NF-κB-dependent pathway, which leads to downregulation of suppressor of cytokine signaling 1 (SOCS1), and thus enhancement of type I IFN signaling, which may exacerbate inflammation [210].”

• cites [210] Wang, 2010, Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1, J. Immunol. sourceSupported

May combine two claims.

Bacterial infection and LPS induce miR-15a/16.

“Both bacterial infection and LPS itself induce miR-15a/16.”

• cites [113] Moon, 2014, miR-15a/16 regulates macrophage phagocytosis after bacterial infection, J. Immunol. sourceSupported

May combine two claims.

Akt1 upregulates let-7e and miR-181c and downregulates miR-155 and miR-125b.

“Protein kinase Akt1 upregulates let-7e and miR-181c but downregulates miR-155 and miR-125b.”

• cites [57] Androulidaki, 2009, The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs, Immunity sourcePartly supported

  The Results (section 1) support Akt1 increasing let-7e and miR-181c and reducing miR-155 in LPS-stimulated macrophages. They also report that active Akt1 increases the LPS-induced suppression of miR-125b, but has no effect on its basal level. Thus the unqualified claim that Akt1 downregulates miR-125b omits a condition that matters. (LLM, conf=0.94)

  Experimental — accuracy not yet measured

May combine two claims.

In mice, miR-15a/16 knockout derepresses PU.1, upregulating TLR4 and modulating Cdc42 and TRAF6.

“In mice miR-15a/16 knock-out derepresses PU.1, which upregulates TLR4, further modulating Rho GTPase Cdc 42 and TRAF6.”

• cites [113] Moon, 2014, miR-15a/16 regulates macrophage phagocytosis after bacterial infection, J. Immunol. sourceSupported

May combine two claims.

Mtb induces miR-155, which targets Rheb, boosts autophagy in macrophages, promotes phagosome maturation, and decreases intracellular mycobacteria survival.

“Mtb induces expression of miR-155, which, by targeting Ras homologue enriched in brain (Rheb), boosts the autophagic response in macrophages, thus promoting the maturation of phagosomes and decreasing the survival rate of intracellular mycobacteria”

• cites [162] Wang, J., Yang, K., Zhou, L., Wu, Y., Zhu, M., Lai, X., Chen, T., Feng, L., and Li, M. (2013). MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb. PLoS Pathog., 9. sourceSupported

May combine two claims.

TLR stimulation downregulates miR-92a, which targets MKK4.

“Stimulation of different TLRs downregulates miR-92a, which targets mitogen-activated protein kinase 4 (MKK4).”

• cites [134] Lai, 2013, MicroRNA-92a negatively regulates Toll-like receptor (TLR)-triggered inflammatory response in macrophages by targeting MKK4 kinase, J. Biol. Chem. sourceSupported

May combine two claims.

These pro-inflammatory effects stimulate E. coli uptake and mitochondrial ROS generation.

“These pro-inflammatory effects stimulate both E. coli uptake and generation of mitochondrial ROS [113].”

• cites [113] Moon, 2014, miR-15a/16 regulates macrophage phagocytosis after bacterial infection, J. Immunol. sourcePartly supported

  The Results (page not provided) report greater E. coli uptake and mitochondrial ROS generation in miR-15a/16-deficient macrophages. The Discussion (page not provided) also reports increased pro-inflammatory cytokines and chemokines, but does not show that those pro-inflammatory effects stimulate either uptake or ROS generation; it discusses other pathways for those outcomes. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Silencing miR-92a increases JNK/c-Jun activation and pro-inflammatory cytokine production in macrophages.

“silencing of miR-92a increases the activation of the JNK/c-Jun pathway and stimulates the production of pro-inflammatory cytokines in macrophages [134]”

• cites [134] Lai, 2013, MicroRNA-92a negatively regulates Toll-like receptor (TLR)-triggered inflammatory response in macrophages by targeting MKK4 kinase, J. Biol. Chem. sourcePartly supported

  The miR-92a Regulates TLR-triggered Inflammatory Response section reports that miR-92a inhibitors increased JNK and c-Jun phosphorylation and LPS-induced TNFα and IL-6 production in macrophages (Figs. 4C and 3E–F). The citing sentence omits the LPS/TLR-stimulation condition under which these effects were shown. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

let-7e targets TLR4 and miR-155 targets SOCS1, leading to LPS tolerance.

“They showed that let-7e targets TLR4 and miR-155 targets SOCS1, thus leading to LPS tolerance [57].”

• cites [57] Androulidaki, 2009, The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs, Immunity sourcePartly supported

  Results §3 confirms that let-7e targets TLR4 and miR-155 targets SOCS1. But Results §§4 and 6 do not support the claim that both targeting actions lead to LPS tolerance: miR-155 increased the LPS response, while mice became tolerant after receiving macrophages treated with let-7e and an inhibitor of miR-155. Page numbers are unavailable in our copy. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

Upon Mtb infection, miR-125b is upregulated and miR-155 is downregulated, decreasing TNF production.

“upon Mtb infection, contrary changes occur, i.e., up-regulation of miR-125b and down-regulation of miR-155 decreases TNF production [142]”

• cites [142] Rajaram, 2011, Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b, Proc. Natl. Acad. Sci. USA sourcePartly supported

  The section on infected macrophages reports that M. tuberculosis increased miR-125b, limited miR-155 relative to M. smegmatis, and yielded lower TNF production. It does not establish that miR-155 was downregulated relative to uninfected macrophages, as the citing sentence implies. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

TLR2/TLR4 stimulation upregulates miR-125a-5p in a MYD88-dependent manner, promoting the M2 phenotype.

“Stimulation of TLR2 and TLR4 leads to upregulation of miR-125a-5p in an MYD88-dependent manner and subsequently promotes the M2 phenotype [138]”

• cites [138] Banerjee, 2013, miR-125a-5p regulates differential activation of macrophages and inflammation, J. Biol. Chem. sourcePartly supported

  The Results and Discussion report that TLR2/TLR4 stimulation upregulates miR-125a-5p and that this induction requires MYD88. The paper also finds that miR-125a-5p enhances M2 marker expression, but that result was measured after IL-4 exposure; it does not show that TLR2/TLR4 stimulation itself subsequently promotes the M2 phenotype. The Results instead describe LPS stimulation as inducing M1 activation. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

LPS induces expression of miR-17, miR-20a, and miR-106a, which collectively target SIRPα.

“Zhu et al. reported that LPS induces expression of miR-17, miR-20a, and miR-106a, which collectively target signal regulatory protein alpha (SIRPα)”

• cites [211] Liu, D.Q., Li, L.M., Guo, Y.L., Bai, R., Wang, C., Bian, Z., Zhang, C.Y., and Zen, K. (2008). Signal regulatory protein alpha negatively regulates beta2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis. PLoS ONE, 3. sourceCould not verify

  The Results and Discussion describe how changing SIRPα levels affects β2-integrin-mediated responses, but do not address the claimed microRNAs. Searches for miR-17, miR-20a, miR-106a, and LPS found no passage saying that LPS induces these microRNAs or that they target SIRPα; the References list an LPS-related study without making that claim. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

May combine two claims.

SYK kinase is crucial for FcγR-mediated phagocytosis and necessary for PI3-kinase activation and regulation of Rac2 and Vav3 activity.

“SYK kinase is crucial for FcγR-mediated phagocytosis and is necessary for PI3-kinase activation, and further regulation of Rac2 and Vav3 activity.”

• cites [214] Li, 2019, Expression profile of microRNAs in porcine alveolar macrophages after Toxoplasma gondii infection, Parasites Vectors sourcePartly supported

  The Discussion says SYK kinases are essential for FcγR-mediated phagocytosis and crucial for downstream PI3-kinase activation. It also says Rac2 and Vav3 play notable roles in the pathway, but does not state that SYK regulates their activity. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Apoptotic neutrophils are phagocytosed by macrophages, and macrophages can undergo apoptosis with clinical consequences such as atherosclerosis.

“Apoptotic neutrophils are phagocytosed by macrophages [216], but macrophages also can undergo apoptosis, which may have important clinical consequences, such as atherosclerosis [217].”

• cites [216] Filep, 2013, Modulation of Neutrophil Apoptosis and the Resolution of Inflammation through β2 Integrins, Front. Immunol.Not checked yet

  Not checked in the free run.

• cites [217] Seimon, 2009, Mechanisms and consequences of macrophage apoptosis in atherosclerosis, J. Lipid Res. sourceSupported

May combine two claims.

LPS stimulation of murine microglia upregulates miR-155, -297b-5p, -302c, -191, -10b, -105, -495, -7a, -670, -1934, -201, -200c-5p, -214-5p, -673, and -141-5p, and downregulates miR-1928, -3474, -383, -192, -1939, -466b-3p, -2134, -1901, -762, -689, -128-5p, -542, -700, -219, and 705.

“LPS stimulation resulted in upregulation of miR-155, -297b-5p, -302c, -191, -10b, -105, -495, -7a, -670, -1934, -201, -200c-5p, -214-5p, -673, and -141-5p, whereas expression of miR-1928, -3474, -383, -192, -1939, -466b-3p, -2134, -1901, -762, -689, -128-5p, -542, -700, -219, and 705 was lowered.”

• cites [227] Freilich, R.W., Woodbury, M.E., and Ikezu, T. (2013). Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia. PLoS ONE, 8. sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

During wound healing, miR-21 induction suppresses PTEN and PDCD4, inhibits LPS-induced NF-κB activation, decreases TNF-α expression, and is anti-inflammatory.

“During wound healing, induction of miR-21 leads to suppression of PTEN and PDCD4, and subsequent inhibition of LPS-induced NF-κB activation and decreased TNF-α expression, thus being anti-inflammatory [121].”

• cites [121] Das, 2014, Engulfment of apoptotic cells by macrophages: A role of microRNA-21 in the resolution of wound inflammation, J. Immunol. sourcePartly supported

  The Results show that miR-21 suppresses PTEN and PDCD4, and that the PTEN pathway reduces LPS-induced NF-κB activation and TNF-α expression in macrophages. But the PDCD4 Results section links its suppression to increased anti-inflammatory IL-10, not to the NF-κB/TNF-α pathway implied by “subsequent.” Page numbers are not available in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Lack of miR-146a results in overactivation of NF-κB, increased myeloid cell recruitment, and more severe Lyme arthritis, but does not affect Lyme carditis.

“Lack of miR-146a results in overactivation of NF-κB, increase in myeloid cell recruitment and more severe Lyme arthritis, whereas it does not affect Lyme carditis.”

• cites [150] Lochhead, R.B., Ma, Y., Zachary, J.F., Baltimore, D., Zhao, J.L., Weis, J.H., O’Connell, R.M., and Weis, J.J. (2014). MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi. PLoS Pathog., 10. sourceSupported

May combine two claims.

miR-466l is upregulated in peripheral blood of sepsis patients and its levels correlate with risk of death.

“MiR-466l is upregulated in the peripheral blood of patients with sepsis, and its levels correlate with risk of death.”

• cites [224] Li, 2013, Plasticity of leukocytic exudates in resolving acute inflammation is regulated by MicroRNA and proresolving mediators, Immunity sourceSupported

May combine two claims.

miR-146a-5p and miR-146b-5p are induced by NF-κB and negatively regulate TRAF6, IRAK1, and IRAK2, inhibiting RIG-I-dependent type I IFN production.

“Expression of miR-146a-5p and miR-146b-5p are induced by NF-κB, and they act as negative regulators of TNF receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK1) [58], and IRAK2, thus inhibiting retinoic acid-inducible gene I (RIG-I)-dependent type I IFN production [222].”

• cites [58] Taganov, 2006, NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses, Proc. Natl. Acad. Sci. USA sourcePartly supported

  The Results report that NF-κB binding sites are required for LPS induction of the miR-146a promoter, and that both miR-146a and miR-146b repress reporters bearing TRAF6 or IRAK1 3′ UTRs. The paper does not establish NF-κB-dependent induction of miR-146b or direct repression of endogenous TRAF6 and IRAK1 proteins. IRAK2 and RIG-I-dependent type I IFN production are attached to a different citation in the citing sentence, so they are not judged here. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [222] Hou, 2009, MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2, J. Immunol. sourcePartly supported

  The section on VSV-induced miR-146a expression reports RIG-I/NF-κB-dependent induction of miR-146a, but says mature miR-146b was not induced in macrophages after VSV infection. The sections on miR-146a targets and target knockdown support regulation of TRAF6, IRAK1, and IRAK2 and reduced VSV-triggered type I IFN production. They do not establish the same mechanism for miR-146b-5p. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

These effects depend on TLR4/TNF-α/TGF-β1/IL-10 signaling and are suppressed by miR-23a-3p downregulation.

“Both are dependent on the TLR4/TNF-α/TGF-β1/IL-10 signaling pathway, and are suppressed by miR-23a-3p downregulation [122].”

• cites [122] Chen, Y.C., Lee, C.P., Hsiao, C.C., Hsu, P.Y., Wang, T.Y., Wu, C.C., Chao, T.Y., Leung, S.Y., Chang, Y.P., and Lin, M.C. (2020). MicroRNA-23a-3p Down-Regulation in Active Pulmonary Tuberculosis Patients with High Bacterial Burden Inhibits Mononuclear Cell Function and Phagocytosis through TLR4/TNF-α/TGF-β1/IL-10 Signaling via Targeting IRF1/SP1. Int. J. Mol. Sci., 21. sourceSupported

May combine two claims.

Lack of miR-146a impairs resolution of inflammation and leads to joint damage.

“Overall, the lack of miR-146a impairs resolution of inflammation and leads to joint damage [150].”

• cites [150] Lochhead, R.B., Ma, Y., Zachary, J.F., Baltimore, D., Zhao, J.L., Weis, J.H., O’Connell, R.M., and Weis, J.J. (2014). MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi. PLoS Pathog., 10. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Microglia activation can be described as M1 (initiated by TLR/IFN-γ, producing proinflammatory cytokines/chemokines) or M2 (initiated by IL-4/IL-13/IL-10, producing IL-10, TGF-β, growth factors).

“As in case of macrophages, microglia activation may be described as M1, initiated by TLR and IFN-γ signaling pathways, characterized by production of proinflammatory cytokines and chemokines, such as TNF-α, IL-6, IL-1β, IL-12, and CCL2, or M2, initiated by IL-4, IL-13, IL-10, and resulting in production of IL-10, TGF-β, and growth factors [225].”

• cites [225] Colonna, 2017, Microglia Function in the Central Nervous System During Health and Neurodegeneration, Annu. Rev. Immunol. sourceSupported

May combine two claims.

In a murine model, during the inflammatory response, miR-466l is first overexpressed in neutrophils, acting proinflammatory, and then overexpressed in macrophages, leading to increase in prostanoids and specialized proresolving mediators (RvD1, RvD5).

“During the inflammatory response, miR-466l is first overexpressed in neutrophils, acting proinflammatory, and then it is overexpressed in macrophages, leading to increase in prostanoids and specialized proresolving mediators (e.g., resolvin D1 [RvD1] and RvD5).”

• cites [224] Li, 2013, Plasticity of leukocytic exudates in resolving acute inflammation is regulated by MicroRNA and proresolving mediators, Immunity sourceSupported

May combine two claims.

miR-125b represses IRF4 and induces CD80 expression, enhancing macrophage antigen-presenting capacity.

“Chaudhuri et al. demonstrated that miR-125b represses IFN regulatory factor 4 (IRF4) and induces CD80 expression, which enhances macrophage antigen presenting cells’ capacities [143].”

• cites [143] Chaudhuri, 2011, MicroRNA-125b potentiates macrophage activation, J. Immunol. sourceSupported

May combine two claims.

miR-106-5p is upregulated by Mtb infection in macrophages and targets cathepsin S mRNA, decreasing lysosomal activity.

“miR-106-5p, a microRNA upregulated by Mtb infection in macrophages and targets cathepsin S (CtsS) mRNA, thus decreasing lysosomal activity [136,198].”

• cites [136] Pires, 2017, Mycobacterium tuberculosis Modulates miR-106b-5p to Control Cathepsin S Expression Resulting in Higher Pathogen Survival and Poor T-Cell Activation, Front. Immunol. sourcePartly supported

  The Results section (‘Mtb Induces the Expression of miR-106b-5p in Human Mø’) reports upregulation during infection, and the Abstract reports that miR-106b-5p targets CtsS mRNA. The cited paper identifies the microRNA as miR-106b-5p, not miR-106-5p, and reports reduced CtsS activity and endolysosomal proteolysis rather than a general decrease in lysosomal activity. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [198] Yang, 2018, miRNAs in immune responses to Mycobacterium tuberculosis infection, Cancer Lett. sourceNot checked — no full text of the source

May combine two claims.

Increased expression of miR-144 in rat macrophages impairs bacterial phagocytic capacity and H2O2 scavenging ability.

“increased expression of miR-144 on a rat macrophage model impaired bacterial phagocytic capacity and H2O2 scavenging ability [146].”

• cites [146] Fan, 2021, HIV Impairs Alveolar Macrophage Function via MicroRNA-144-Induced Suppression of Nrf2, Am. J. Med. Sci. sourceSupported

May combine two claims.

Overexpression of let-7c promotes the M2 phenotype and increases phagocytosis of apoptotic cells, whereas knockdown decreases it.

“Overexpression of let-7c, by promoting the M2 phenotype, increases phagocytosis of apoptotic cells, whereas its knockdown decreases it [110].”

• cites [110] Banerjee, 2013, MicroRNA let-7c regulates macrophage polarization, J. Immunol. sourceSupported

May combine two claims.

Overexpression of miR-155 enhances ROS production and miR-155 is a potent promoter of M1 polarization.

“ROS production was also enhanced via overexpression by miR-155 [156], which was identified as a potent promoter of M1 polarization.”

• cites [156] Jia, 2017, Gold nanoparticle-based miR155 antagonist macrophage delivery restores the cardiac function in ovariectomized diabetic mouse model, Int. J. Nanomed. sourcePartly supported

  The Results section (page unavailable) calls miR155 a potent M1 promoter and reports that miR155 transfection increased IL-1β while reducing IL-10 in macrophages. The cited paper does not report that miR-155 overexpression enhances ROS production; searches for ROS and reactive oxygen species found no supporting passage. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

FcγR-mediated phagocytosis may be modulated by miR-29a/b/c, and Igf1 is a target gene for miR-29a/b/c.

“Interestingly, FcγR-mediated phagocytosis may also be modulated by miR-29a/b/c. Insulin like growth factor 1 (Igf1) was identified as the target gene for miR-29a/b/c”

• cites [215] He, 2018, Bioinformatics analysis of microarray data to reveal the pathogenesis of brain ischemia, Mol. Med. Rep. sourcePartly supported

  The Discussion identifies Igf1 as a target gene regulated by miR-29A/B/C, although it says the relationship in brain ischemia has not been experimentally validated. It associates FcγR-mediated phagocytosis with RAC2, not miR-29A/B/C, so the proposed modulation of that pathway by miR-29A/B/C is unsupported. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

NF-κB activation by LPS initiates transcription of miR-9-1, which subsequently downregulates NF-κB.

“It was shown that NF-κB, upon its activation in response to LPS, initiates transcription of miR-9-1, which subsequently downregulates NF-κB [112].”

• cites [112] Bazzoni, 2009, Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals, Proc. Natl. Acad. Sci. USA sourcePartly supported

  The Results show that LPS-induced miR-9-1 transcription depends on NF-κB and that miR-9 reduces NFKB1/p105 expression in human monocytes. The paper proposes feedback control of NF-κB-dependent responses, but it does not show that miR-9 downregulates NF-κB as a whole. The supplied passages have section labels but no page numbers. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

Mtb infection downregulates miR-26a, derepressing KLF4, impairing Mtb trafficking to lysosomes, and contributing to Mtb survival.

“Mtb infection leads to downregulation of miR-26a and subsequent derepression of KLF4, which further impairs trafficking of Mtb to lysosomes, thus contributing to Mtb survival [126].”

• cites [126] Sahu, S.K., Kumar, M., Chakraborty, S., Banerjee, S.K., Kumar, R., Gupta, P., Jana, K., Gupta, U.D., Ghosh, Z., and Kundu, M. (2017). MicroRNA 26a (miR-26a)/KLF4 and CREB-C/EBPβ regulate innate immune signaling, the polarization of macrophages and the trafficking of Mycobacterium tuberculosis to lysosomes during infection. PLoS Pathog., 13. sourceSupported

May combine two claims.

Borrelia burgdorferi infection upregulates miR-146a in murine joint tissue, suppressing IRAK1 and TRAF6.

“Lochhead et al. reported that Borrelia burgdorferi infection leads to upregulation of miR-146a in murine joint tissue (suppressing IRAK1 and TRAF6, as mentioned before).”

• cites [150] Lochhead, R.B., Ma, Y., Zachary, J.F., Baltimore, D., Zhao, J.L., Weis, J.H., O’Connell, R.M., and Weis, J.J. (2014). MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi. PLoS Pathog., 10. sourcePartly supported

  The Abstract reports miR-146a upregulation in joint tissue from three mouse strains infected with B. burgdorferi. The Results section on bone marrow-derived macrophages supports miR-146a-mediated repression of TRAF6, but reports similar IRAK1 protein levels with and without miR-146a; it does not establish suppression of both proteins in joint tissue. No page numbers are available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

miR-146a knockout mice develop LPS hypersensitivity, autoimmune disorders, myeloproliferative disorders, and lymphomas due to NF-κB dysregulation.

“Mice with miR-146a knock-out develop LPS hypersensitivity, autoimmune disorders, myeloproliferative disorders, and lymphomas [219] due to NF-κB dysregulation [220].”

• cites [219] Boldin, 2011, miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice, J. Exp. Med. sourceSupported
• cites [220] Zhao, 2011, NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies, Proc. Natl. Acad. Sci. USA sourcePartly supported

  The Abstract reports that miR-146a knockout mice develop myeloproliferation and some lymphomas, and that NF-κB p50 ablation suppresses myeloproliferation. This supports NF-κB dysregulation as a cause of the myeloproliferative disease, but the passage does not establish it as the cause of LPS hypersensitivity, autoimmune disorders, or lymphomas. The phenotype list is separately cited to [219]. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

miR-146a expression does not affect bacterial number in tissue, but macrophage uptake of B. burgdorferi is higher in miR-146a knockout.

“expression of miR-146a does not affect the number of bacteria in the tissue, whereas macrophage uptake of B. burgdorferi is higher in the case of miR-146a knock-out.”

• cites [150] Lochhead, R.B., Ma, Y., Zachary, J.F., Baltimore, D., Zhao, J.L., Weis, J.H., O’Connell, R.M., and Weis, J.J. (2014). MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi. PLoS Pathog., 10. sourcePartly supported

  The Results section on phagocytic activity reports greater association with B. burgdorferi in miR-146a-knockout macrophages, supporting the uptake claim. But the Results section on host defense reports fewer bacteria in infected knockout joints, although burdens in heart and ear tissue were similar. The claim that tissue bacterial numbers are unaffected is therefore too broad. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

In a murine model, microglia aging decreases NF-κB activation, impairing phagocytic activity, accompanied by decreasing expression of miR-124 and miR-155.

“Caldeira et al. showed in a murine model that microglia aging leads to decreased activation of NF-κB, which impairs phagocytic activity, and these changes are accompanied by decreasing expression of miR-124 and miR-155 [254].”

• cites [254] Caldeira, 2014, Microglia change from a reactive to an age-like phenotype with the time in culture, Front. Cell. Neurosci. sourcePartly supported

  The Results sections on NF-κB activation, phagocytic ability, and reactive ability report lower NF-κB activation, reduced bead engulfment, and lower miR-124 and miR-155 expression in mouse microglia after 16 days in culture. The paper describes these cells as age-like; it does not show that reduced NF-κB activation causes the loss of phagocytic activity or establish the same changes in aging mice. The indexed copy provides section labels but no page numbers. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

In vivo inhibition of miR-155 in mice during stroke leads to derepression of SOCS-1, SHIP-1, and C/EBP-β and increased STAT-3 phosphorylation, resulting in upregulation of IL-10, IL-4, IL-6, MIP-1α, IL-5, and IL-17.

“It was further demonstrated that in vivo inhibition of miR-155 in mice during an experiment on strokes leads to derepression of SOCS-1, SHIP-1 (interaction demonstrated in [158]) and C/EBP-β (interaction demonstrated in [245]) and increased phosphorylation levels of cytokine signaling regulator STAT-3. These changes result in upregulation of anti-inflammatory cytokines, namely IL-10, IL-4, IL-6, M”

• cites [246] Lordkipanidze, 2016, In vivo inhibition of miR-155 significantly alters post-stroke inflammatory response, J. Neuroinflammation sourcePartly supported

  The Results sections report increased SOCS-1, SHIP-1, and C/EBP-β at 7 days after stroke, and increased levels of all six listed cytokines at 14 days. But STAT-3 phosphorylation decreased at 7 days and increased only at 14 days, when SOCS-1 and SHIP-1 were no longer elevated. The paper describes possible links among these changes rather than establishing that they caused the cytokine increases; it also does not classify all six cytokines as anti-inflammatory. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

May combine two claims.

miR-34a targets TREM2, and in retina samples miR-34a expression is higher in AMD patients while TREM2 expression is lower.

“A team led by Lukiw showed that miR-34a targets a triggering receptor expressed in myeloid/microglial cells-2 (TREM2). Using retina samples, they confirmed that expression of miR-34a was higher in those obtained from patients with age-related macular degeneration (AMD), whereas TREM2 expression was lower.”

• cites [229] Bhattacharjee, S., Zhao, Y., Dua, P., Rogaev, E.I., and Lukiw, W.J. (2016). microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration. PLoS ONE, 11. sourceSupported

May combine two claims.

Hypoxia and glucose deprivation downregulates miR-181c, derepressing TLR4 and activating NF-κB signaling.

“Hypoxia and glucose deprivation leads to downregulation of miR-181c, which leads to derepression of TLR4 and activation of NF-κB signaling [205].”

• cites [205] Zhang, 2015, MicroRNA-181c negatively regulates the inflammatory response in oxygen-glucose-deprived microglia by targeting Toll-like receptor 4, J. Neurochem. sourceSupported

May combine two claims.

miR-146a and miR-155 are upregulated in E. coli-infected astrocytes; miR-146a targets IRAK1 and TRAF6, miR-155 targets TAB2, and they collectively inhibit EGFR-NF-κB signaling.

“Both miR-146a and miR-155 are upregulated in E. coli-infected astrocytes, taking part in fine-tuning of inflammatory response by targeting IRAK1 and TRAF6 (miR-146a), and TAB2 (miR-155), and collectively inhibiting the EGFR–NF-κB signaling pathway.”

• cites [236] Yang, 2021, miR-155 and miR-146a collectively regulate meningitic Escherichia coli infection-mediated neuroinflammatory responses, J. Neuroinflammation sourceSupported

May combine two claims.

Overexpression of miR-34a in C8B4 mouse microglia impairs phagocytosis of Aβ42 peptides, contributing to AMD progression.

“Using C8B4 mice microglia cells, the authors demonstrated that overexpression of miR-34a impaired phagocytosis of Aβ42 peptides, derivatives of beta-amyloid precursor protein (βAPP), thus contributing to AMD progression [229].”

• cites [229] Bhattacharjee, S., Zhao, Y., Dua, P., Rogaev, E.I., and Lukiw, W.J. (2016). microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration. PLoS ONE, 11. sourcePartly supported

  The Results section reports that a miRNA-34a mimic reduced TREM2 and Aβ42 internalization in microglial cells; the Fig. 6 description identifies the cells as murine C8B4 cells. The Discussion suggests this mechanism contributes to AMD-related amyloidogenesis, but the cell experiment did not demonstrate an effect on AMD progression. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Docosahexaenoic acid affects phenotype by stimulating the M2 phenotype, and this effect results from upregulation of miR-124.

“Yip et al. showed that docosahexaenoic acid (DHA) also affects the phenotype by stimulation of the M2 phenotype. The observed mechanisms resulted from upregulation of miR-124 [233].”

• cites [233] Yip, 2019, Docosahexaenoic acid reduces microglia phagocytic activity via miR-124 and induces neuroprotection in rodent models of spinal cord contusion injury, Hum. Mol. Genet. sourcePartly supported

  The section “DHA enhances both M1 and M2 microglia/macrophage phenotypes in spinal cord contusion injury” reports increased M2 markers after DHA treatment, but also increased M1 markers. “DHA enhances microglial miRNA-124 expression” reports increased miR-124 and suggests that it modulates microglial activity; it does not establish that miR-124 upregulation caused the observed M2 increase. Page numbers were not available in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

miR-155 is induced by LPS in mouse N9 microglia cell line and primary cultures, and miR-155 targets SOCS1.

“Cardoso et al., based on findings in other myeloid-derived cells, demonstrated that miR-155 is induced by LPS in a mouse N9 microglia cell line and in primary cultures. Similar to other authors [244], they confirmed targeting of the suppressor of the cytokine signaling 1 gene (SOCS1) by miR-155.”

• cites [237] Cardoso, 2012, miR-155 modulates microglia-mediated immune response by down-regulating SOCS-1 and promoting cytokine and nitric oxide production, Immunology sourceNot checked — no full text of the source
• cites [244] Jiang, 2010, MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene, Cancer Res. sourceSupported

May combine two claims.

IL-4 stimulation of murine microglia upregulates miR-145, -297b-5p, and miR-214, and downregulates miR-1939, -711, -1224, -200a-5p, -762, -2138, -2861, -1971, -133a, -2132, -2135, -2133, -124, -2137, and -325.

“Upon IL-4 stimulation, the authors observed upregulation of miR-145, -297b-5p, and miR-214, accompanied by reduced expression of miR-1939, -711, -1224, -200a-5p, -762, -2138, -2861, -1971, -133a, -2132, -2135, -2133, -124, -2137, and -325 [227].”

• cites [227] Freilich, R.W., Woodbury, M.E., and Ikezu, T. (2013). Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia. PLoS ONE, 8. sourceSupported

May combine two claims.

Stimulation with IFNγ, IL-1α, and MARCO (but not IL-1β) activates p53, upregulates miR-155, which downregulates c-Maf, inducing an inflammatory response.

“Su et al. demonstrated that stimulation with IFNγ, IL-1α and MARCO, but not with IL-1β, leads to activation of p53, and subsequent upregulation of miR-155, which in turn downregulates c-Maf, thus inducing an inflammatory response.”

• cites [230] Su, 2014, The p53 transcription factor modulates microglia behavior through microRNA-dependent regulation of c-Maf, J. Immunol. sourcePartly supported

  The Results section reports that IFNγ induces miR-155 in a p53-dependent manner and that miR-155 suppresses c-Maf. But it treats IL-1α, MARCO, and IL-1β as genes measured after IFNγ treatment, not as stimuli: IL-1α and MARCO showed miR-155-dependent induction, whereas IL-1β did not. The cited paper therefore supports the pathway but not the claim's list of activating stimuli. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

May combine two claims.

miR-155 may impair β-amyloid1-42 clearance; its knockout enhances transmembrane transport of fibrillar β-amyloid and directs it to low-pH compartments for catabolism.

“MiR-155 may impair β-amyloid1-42 clearance, as its knock-out enhances transmembrane transport of fibrillar β-amyloid and promotes directing it towards low-pH compartments for subsequent catabolism [239].”

• cites [239] Aloi, 2021, The pro-inflammatory microRNA miR-155 influences fibrillar β-Amyloid(1) (-42) catabolism by microglia, Glia sourceSupported

May combine two claims.

In mice, miR-21 knockout decreases osteoclast number and resorption activity, causing decreased age- and estrogen-deficiency-related bone loss.

“in mice, miR-21 knock-out results in a decreased number and resorption activity of osteoclasts, causing decreased bone-loss that is both age and estrogen-deficiency-related (Table 3).”

• cites [260] Hu, 2017, miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice, Sci. Rep. sourceSupported

May combine two claims.

Suppression of miR-146a and miR-155 upon E. coli infection aggravates astrocyte and microglia activation and decreases mouse survival time without affecting bacterial loads.

“Experimental suppression of these microRNAs upon E. coli infection aggravated astrocyte and microglia activation and decreased mouse survival time without affecting bacterial loads [236].”

• cites [236] Yang, 2021, miR-155 and miR-146a collectively regulate meningitic Escherichia coli infection-mediated neuroinflammatory responses, J. Neuroinflammation sourceSupported

May combine two claims.

Dexmedetomidine's anti-inflammatory effect is mediated by miR-340, which targets NF-κB, suppresses pro-inflammatory cytokines, induces IL-10, and decreases phagocytosis.

“Using a BV2 cell line, it was demonstrated that its anti-inflammatory effect is mediated by miR-340, which targets NF-κB, and thus suppresses pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-2 and IL-12), inducing anti-inflammatory IL-10, and decreasing phagocytosis [241].”

• cites [241] Bao, 2019, Dexmedetomidine Attenuates Neuroinflammation In LPS-Stimulated BV2 Microglia Cells Through Upregulation Of miR-340, Drug Des. Dev. Ther. sourceSupported

May combine two claims.

miR-302d-3p is overexpressed in RPEs of AMD patients and targets CDNK1A and p21Waf1/Cip1, inducing RPE dedifferentiation, cell cycle progression, proliferation, migration, and inhibiting phagocytosis.

“MiR-302d-3p is overexpressed in RPEs of AMD patients. It targets products of CDNK1A and p21Waf1/Cip1, inducing RPE dedifferentiation, cell cycle progression, proliferation, migration, and inhibiting phagocytosis [272].”

• cites [272] Jiang, 2018, c-Jun-mediated microRNA-302d-3p induces RPE dedifferentiation by targeting p21(Waf1/Cip1), Cell Death Dis. sourcePartly supported

  The Results sections on CDKN1A targeting and RPE phagocytosis, together with the Discussion, support the reported effects on RPE differentiation, cell-cycle progression, proliferation, migration, and phagocytosis. They do not establish that miR-302d-3p is overexpressed in RPE cells from AMD patients; the experiments described used cultured RPE cells. The gene is CDKN1A (not CDNK1A), and p21Waf1/Cip1 is its encoded protein, not a separate target. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

miR-194 is physiologically expressed in rat RPE, targets ZEB1, and exogenous administration of miR-194 alleviates proliferative vitreoretinopathy.

“MiR-194 is physiologically expressed in rat RPE. It targets zinc finger E-box binding homeobox 1 (ZEB1) and is in silico predicted to regulate numerous cell functions, among others, phagocytosis. Indeed, exogenous administration of miR-194 alleviates proliferative vitreoretinopathy [267].”

• cites [267] Cui, 2019, miR-194 suppresses epithelial-mesenchymal transition of retinal pigment epithelial cells by directly targeting ZEB1, Ann. Transl. Med. sourceSupported

May combine two claims.

miR-184 expression is lower in RPE from AMD patients than healthy donors, leading to derepression of ezrin, which downregulates LAMP1, impairing phagocytosis and contributing to vision loss.

“Expression of miR-184 is lower in RPE from AMD patients than healthy donors. This lower level leads to derepression of its target, ezrin, which, in turn, downregulates lysosomal-associated membrane protein 1, impairing phagocytosis and contributing to vision loss [266].”

• cites [266] Murad, 2014, miR-184 regulates ezrin, LAMP-1 expression, affects phagocytosis in human retinal pigment epithelium and is downregulated in age-related macular degeneration, FEBS J. sourcePartly supported

  The ‘miR-184 is downregulated in AMD’ section reports lower miR-184 in RPE from AMD donors. The Discussion (p. 5258) reports that inhibiting miR-184 increased ezrin, lowered LAMP-1, and reduced phagocytic activity in cultured RPE cells. But the paper could not detect an ezrin increase in AMD donor RPE, describes the proposed chain affecting phagocytosis as speculative, and does not establish that it contributes to vision loss. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Upregulation of miR-382-5p may contribute to AMD pathogenesis by promoting dedifferentiation, proliferation, and ROS production while impairing phagocytosis, and miR-382-5p is regulated by circNR3C1.

“Similarly, upregulation of miR-382-5p may contribute to pathogenesis of AMD through promotion of dedifferentiation, proliferation, and reactive oxygen species production, whereas phagocytosis is impaired. This microRNA is regulated by circNR3C1, which acts as an endogenous sponge [273].”

• cites [273] Chen, 2020, Circular Noncoding RNA NR3C1 Acts as a miR-382-5p Sponge to Protect RPE Functions via Regulating PTEN/AKT/mTOR Signaling Pathway, Mol. Ther. J. Am. Soc. Gene Ther. sourceSupported

May combine two claims.

Decreased miR-145 leads to dedifferentiation of vascular smooth muscle cells and their increased phagocytic function.

“These changes lead to dedifferentiation of vascular smooth muscle cells and their increased phagocytic function [277].”

• cites [277] Vengrenyuk, 2015, Cholesterol loading reprograms the microRNA-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype, Arterioscler. Thromb. Vasc. Biol. sourcePartly supported

  The Results sections on miR-143/145 and VSMC function report that cholesterol loading lowers both miRNAs, shifts VSMCs away from their contractile phenotype, and increases bead uptake relative to control VSMCs. The paper does not show that decreased miR-145 alone causes the increased phagocytosis; the cholesterol-loaded cells also remain much less phagocytic than macrophages. Page numbers were not available in our copy. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

Lack of miR-211 upregulates ezrin, causing defective lysosomal biogenesis and degradative capacity, whereas its upregulation increases lysosome number and stimulates fusion with phagosomes.

“Lack of miR-211 also results in upregulation of ezrin and subsequent defective lysosomal biogenesis and degradative capacity. On the other hand, its upregulation results in increased lysosome number and stimulates their fusion with phagosomes [270].”

• cites [270] Naso, 2020, Light-responsive microRNA miR-211 targets Ezrin to modulate lysosomal biogenesis and retinal cell clearance, EMBO J. sourcePartly supported

  The sections ‘miR-211 controls autophagic flux in vitro’ and ‘Ezrin overexpression suppresses lysosomal biogenesis and function in vitro’ support the link between miR-211 loss, increased Ezrin, and impaired lysosomal biogenesis and degradative function. The former section also reports more lysosomes after miR-211 overexpression, but specifically finds increased fusion of lysosomes with autophagosomes, not phagosomes. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

miR-145 positively regulates myocardin and its expression is decreased in atherosclerotic lesions.

“It was shown that expression of miR-145, which positively regulates myocardin, is decreased in atherosclerotic lesions (Table 6) [276].”

• cites [276] Cordes, 2009, miR-145 and miR-143 regulate smooth muscle cell fate and plasticity, Nature sourceSupported

May combine two claims.

Vascular smooth muscle cells perform nonprofessional phagocytosis and take part in the development of atherosclerotic plaques.

“Vascular smooth muscle cells are able to perform nonprofessional phagocytosis and take part in the development of atherosclerotic plaques [106].”

• cites [106] Sorokin, 2020, Role of Vascular Smooth Muscle Cell Plasticity and Interactions in Vessel Wall Inflammation, Front. Immunol. sourceSupported

May combine two claims.

PU.1 upregulates miR-424, which suppresses the transcriptional factor NFI-A, subsequently stimulating monocyte differentiation through differentiation-specific genes such as M-CSFr.

“PU.1 upregulates miR-424, which suppresses the transcriptional factor NFI-A, subsequently stimulating monocyte differentiation through differentiation-specific genes such as M-CSFr [187].”

• cites [187] Rosa, 2007, The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation, Proc. Natl. Acad. Sci. USA sourceNot checked — no full text of the source

May combine two claims.

Macrophages and granulocytes are professional phagocytes and each may be a cellular target for microRNAs.

“Both macrophages and granulocytes are called professional phagocytes, and each may be a cellular target for microRNAs, but only macrophages are considered as appropriate for potential experimental transfection [53].”

• cites [53] Mehta, 2016, MicroRNAs as regulatory elements in immune system logic, Nat. Reviews. Immunol. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

MicroRNAs are short non-coding RNAs that regulate gene expression and act as important regulators of cellular phenotype and function.

“MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and thus act as important regulators of cellular phenotype and function.”

• cites [1] Lee, 1993, The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14, Cell sourceNot checked — no full text of the source
• cites [2] Wightman, 1993, Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans, Cell sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A single microRNA can target numerous mRNAs, and a single mRNA can be targeted by numerous microRNAs.

“however, a single microRNA can target numerous mRNAs, and a single mRNA can be targeted by numerous microRNAs [10].”

• cites [10] Krek, 2005, Combinatorial microRNA target predictions, Nat. Genet. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Polarization to M1 macrophages is related to their inflammatory functions and is necessary for performing phagocytosis.

“Polarization to M1 macrophages is related to their inflammatory functions. Thus it is necessary for performing phagocytosis.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Most documented microRNAs are involved in the promotion of the pro-inflammatory phenotype-M1.

“Most documented microRNAs are involved in the promotion of the pro-inflammatory phenotype—M1.”

May combine two claims.

Both M1 and M2 phenotypes play important roles in phagocytosis, and both are promoted by different stimuli such as bacterial components, cytokines, or other molecules.

“Both phenotypes play important roles in phagocytosis, and both are promoted by different stimuli such as bacterial components, cytokines, or other molecules.”

May combine two claims.

LPS stimulation activates AKT1, causing repression of miR-155 and miR-125b, and induction of let-7e, which negatively regulates TLR4.

“LPS stimulation also activates AKT1, causing repression of miR-155 and miR-125b, and induction of let-7e, which negatively regulates TLR4.”

• cites [55] Taganov, 2007, MicroRNA-155 is induced during the macrophage inflammatory response, Proc. Natl. Acad. Sci. USA sourceNot checked — no full text of the source

May combine two claims.

MicroRNAs regulate phagocytosis at different levels, including macrophage polarization, phagosome maturation, reactive oxygen species production, and cytokine synthesis.

“In this review, we discuss the current knowledge regarding the influence of microRNAs on phagocytosis, which may be exerted on different levels, such as through macrophages polarization, phagosome maturation, reactive oxygen species production and cytokines synthesis.”

May combine two claims.

Phagocytosis performed by macrophages can be divided into several steps, and microRNAs play a role in regulation of all of them through regulation of numerous proteins.

“It can be divided into several steps, and microRNAs play a role in the regulation of all of them through regulation of numerous proteins, as shown in Table 1 and discussed below.”

May combine two claims.

Pathogen infection, phagocytosis or developing inflammation are directly dependent on dynamic regulation of microRNA expression in macrophages.

“Thus, pathogen infection, phagocytosis or developing inflammation are directly dependent on it.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The M1 phenotype is stimulated by lipopolysaccharide (LPS) and proinflammatory cytokines, such as INF-γ and TNF-α.

“The M1 phenotype is stimulated by lipopolysaccharide (LPS) and proinflammatory cytokines, such as INF-γ and TNF-α.”

May combine two claims.

miR-125a-5p, miR-762, and miR-484 promote M2 phenotype.

“Similar mechanisms were identified for miR-125a-5p, miR-762, and miR-484, also classified as promoting M2 phenotype [139].”

• cites [139] Terrazas, 2019, Taenia crassiceps-Excreted/Secreted Products Induce a Defined MicroRNA Profile that Modulates Inflammatory Properties of Macrophages, J. Immunol. Res.Not checked yet

  Not checked in the free run.

May combine two claims.

M2c macrophages express high levels of miR-125b-5p, miR-125a-5p, and miR-99b and uniquely low levels of miR-200a-3p.

“M2c macrophages express high levels of miR-125b-5p, miR-125a-5p, and miR-99b and uniquely low levels of miR-200a-3p [196].”

• cites [196] Bradley, 2014, Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages, Physiol. Genom. sourceNot checked — no full text of the source

May combine two claims.

M2a macrophages display high levels of miR-193b-3p and miR-511, and low expression of miR-181a-5p and miR-181b-5p.

“M2a macrophages display high levels of miR-193b-3p and miR-511, and low expression of miR-181a-5p and miR-181b-5p.”

• cites [196] Bradley, 2014, Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages, Physiol. Genom. sourceNot checked — no full text of the source

May combine two claims.

M1 macrophages present high expression of miR-146a-5p, miR-29b-3p, and miR-147b, and low expression of miR-221-3p.

“M1 macrophages present high expression of miR-146a-5p, miR-29b-3p, and miR-147b, and low expression of miR-221-3p.”

• cites [196] Bradley, 2014, Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages, Physiol. Genom. sourceNot checked — no full text of the source

May combine two claims.

miR-33 is overexpressed in M1, thus promoting pro-inflammatory functions.

“Expression of miR-33 is also overexpressed in M1, thus promoting pro-inflammatory functions [132].”

• cites [132] Ouimet, 2015, MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis, J. Clin. Investig. sourceNot checked — no full text of the source

May combine two claims.

miR-145-5p was uniquely upregulated in M1, miR-181b-5p was uniquely downregulated in M2a, and miR-200a-3p was exclusively downregulated in M2c macrophages.

“MiR-145-5p was uniquely upregulated in M1, whereas miR-181b-5p was uniquely downregulated in M2a cells, and miR-200a-3p was exclusively downregulated in M2c macrophages.”

• cites [196] Bradley, 2014, Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages, Physiol. Genom. sourceNot checked — no full text of the source

May combine two claims.

IL-16 stimulates macrophage polarization into M2 by enhancing IL-10, IL-1a and IL-6 expression, and miR-145 is involved in this process by targeting IL-16 and stimulating IL-10 synthesis.

“IL-16 stimulates macrophage polarization into M2 enhancing IL-10, IL-1a and IL-6 expression, and Mir-145 is involved in this process by targeting IL-16 and stimulating IL-10 synthesis [147].”

• cites [147] Huang, 2019, IL-16 regulates macrophage polarization as a target gene of mir-145-3p, Mol. Immunol. sourceNot checked — no full text of the source

May combine two claims.

Macrophages secrete miR-21-containing exosomes, spreading the reaction to other macrophages, mainly through polarization towards the pro-inflammatory phenotype, as in the case of miR-27a.

“Macrophages are capable of secreting miR-21-containing exosomes, thus spreading the reaction to other macrophages [117], mainly through polarization towards the pro-inflammatory phenotype [128] as in the case of miR-27a.”

• cites [117] Madhyastha, 2021, MicroRNA 21 Elicits a Pro-inflammatory Response in Macrophages, with Exosomes Functioning as Delivery Vehicles, Inflammation sourceNot checked — no full text of the source
• cites [128] Saha, 2016, MicroRNA Cargo of Extracellular Vesicles from Alcohol-exposed Monocytes Signals Naive Monocytes to Differentiate into M2 Macrophages, J. Biol. Chem. sourceNot checked — no full text of the source

May combine two claims.

miR-500a-5p and miR-502-3p were upregulated in M2a macrophages; miR-21-5p, miR-22-3p, and miR146b-5p were upregulated, and miR-339-3p was downregulated in M2c cells.

“miR-500a-5p and miR-502–3p were upregulated in M2a macrophages; miR-21-5p, miR-22-3p, and miR146b-5p were upregulated, and miR-339-3p was downregulated in M2c cells.”

• cites [196] Bradley, 2014, Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages, Physiol. Genom. sourceNot checked — no full text of the source

May combine two claims.

KLF4 drives M2 polarization and regulates the expression of interleukin-10, and is targeted by miR-26a.

“KLF4, a transcription factor that drives M2 polarization and regulates the expression of interleukin-10, is a crucial factor of the polarization course [199] and is targeted by miR-26a.”

• cites [199] Liu, 2007, KLF4 regulates the expression of interleukin-10 in RAW264.7 macrophages, Biochem. Biophys. Res. Commun. sourceNot checked — no full text of the source

May combine two claims.

miR-146a-5p, miR-193a-5p, and miR-29b-3p were upregulated, and miR-629-5p was downregulated in M1 cells.

“MiR-146a-5p, miR-193a-5p, and miR-29b-3p were upregulated, and miR-629-5p was downregulated in M1 cells.”

• cites [196] Bradley, 2014, Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages, Physiol. Genom. sourceNot checked — no full text of the source

May combine two claims.

During Mtb infection, miR-26a is downregulated, leading to upregulation of KLF4 and stimulation of the M2 phenotype.

“Interestingly, during Mtb infection, miR-26a is downregulated, leading to upregulation of KLF4 and stimulation of the M2 phenotype [198].”

• cites [198] Yang, 2018, miRNAs in immune responses to Mycobacterium tuberculosis infection, Cancer Lett. sourceNot checked — no full text of the source

May combine two claims.

Upregulation of miR-615-3p increases phagocytosis of E. coli by macrophages, while its silencing reduces it.

“Upregulation of miR-615-3p increases phagocytosis of E. coli by macrophages, while its silencing reduces this.”

• cites [179] Jiang, 2011, miR-615-3p promotes the phagocytic capacity of splenic macrophages by targeting ligand-dependent nuclear receptor corepressor in cirrhosis-related portal hypertension, Exp. Biol. Med. sourceNot checked — no full text of the source

May combine two claims.

Mycobacterium bovis BCG stimulates the TLR2-PI3K-PKCδ-MAPK pathway, overexpresses miR-155, indirectly upregulates PUMA, NOXA, BID, BIM, BAK1, and SMAC, leading to apoptosis and immunity.

“Mycobacterium bovis BCG, a strain used in vaccines, stimulates the TLR2-PI3K-PKCδ-MAPK pathway with subsequent overexpression of miR-155, further resulting in indirect (i.e., miR-155 targets PKI-α, a negative regulator of PKA), upregulation of PUMA, NOXA, BID, BIM, BAK1, and SMAC, and eventually to apoptosis, which results in acquiring immunity [209].”

• cites [209] Ghorpade, 2012, MicroRNA-155 is required for Mycobacterium bovis BCG-mediated apoptosis of macrophages, Mol. Cell. Biol. sourceNot checked — no full text of the source

May combine two claims.

LPS stimulation of murine RAW264.7 macrophages upregulates miR-155 and downregulates miR-125b.

“LPS stimulation of murine RAW264.7 macrophages resulted in upregulation of miR-155 and down-regulation of miR-125b.”

• cites [141] Tili, 2007, Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock, J. Immunol. sourceNot checked — no full text of the source

May combine two claims.

miR-155 downregulates IKKε, FADD, and Ripk1.

“miR-155 downregulates IKKε, FADD, and Ripk1”

• cites [141] Tili, 2007, Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock, J. Immunol. sourceNot checked — no full text of the source

May combine two claims.

In P. aeruginosa keratitis, miR-155 is enhanced, and suppression of Rheb decreases phagocytosis and phagosomal killing of P. aeruginosa.

“Expression of miR-155 is also enhanced in P. aeruginosa keratitis, but in this setting the resulting suppression of Rheb decreases both phagocytosis and phagosomal killing of P. aeruginosa [163].”

• cites [163] Yang, 2014, miR-155 suppresses bacterial clearance in Pseudomonas aeruginosa-induced keratitis by targeting Rheb, J. Infect. Dis. sourceNot checked — no full text of the source

May combine two claims.

miR-582-5p and miR-223 inhibit apoptosis by suppressing FOXO1 and FOXO3, and let-7b-5p targets the 3′-UTR of Fas.

“miR-582-5p and miR-223 inhibited apoptosis by suppression FOXO1 and FOXO3. In turn, let-7b-5p has been identified as a microRNA targeting the 3′-UTR of Fas, a protein with a central role in the regulation of apoptosis [198].”

• cites [198] Yang, 2018, miRNAs in immune responses to Mycobacterium tuberculosis infection, Cancer Lett. sourceNot checked — no full text of the source

May combine two claims.

LPS treatment of human peripheral blood mononuclear cells via MyD88 and NF-κB upregulates miR-21, which downregulates TLR4 via PDCD4.

“Treatment of human peripheral blood mononuclear cells with LPS by MyD88 and NF-κB upregulates miR-21, which downregulates TLR4 via PDCD4 [120].”

• cites [120] Sheedy, 2010, Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21, Nat. Immunol. sourceNot checked — no full text of the source

May combine two claims.

Reduced secretion of TNF-α and IL-8 and downregulation of PKC-α suppress superoxide generation as consequences of overexpression of miR-24, miR-30b, and miR-142-3p in macrophages.

“reduced secretion of the pro-inflammatory cytokines TNF-α and IL-8 and down-regulation of PKC-α suppressed superoxide generation. Both effects are consequences of overexpression of miR-24, miR-30b and miR-142-3p in macrophages [123].”

• cites [123] Naqvi, 2016, MicroRNA target Fc receptors to regulate Ab-dependent Ag uptake in primary macrophages and dendritic cells, Innate Immun. sourceNot checked — no full text of the source

May combine two claims.

In zebrafish, overexpression of miR-124 reduces microglia motility and phagocytosis, causing accumulation of residual apoptotic cell bodies in the optic tectum.

“In a zebrafish model it was demonstrated that overexpression of miR-124 reduces microglia motility and phagocytosis, which resulted in accumulation of residual apoptotic cell bodies in the optic tectum [234].”

• cites [234] Svahn, 2016, miR-124 Contributes to the functional maturity of microglia, Dev. Neurobiol. sourceNot checked — no full text of the source

May combine two claims.

miR-98 reduces ischemia/reperfusion damage by improving blood-brain barrier tightness and reducing proinflammatory Ly6CHI leukocytes and M1 microglia.

“other studies showed that miR-98 takes part in reducing ischemia/reperfusion damage due to its positive influence on the tightness of the blood-brain barrier and reduction of the prevalence of proinflammatory Ly6CHI leukocytes and M1 microglia within the impacted area [252].”