Anabolic effect of plant brassinosteroid

May combine two claims.

The anabolic response of L6 cells to HB treatment was abolished by the addition of both Akt inhibitor triciribin and PI3K inhibitor LY294002, reducing the response from 50% over control to only 4%.

“The anabolic response of L6 cells to HB treatment was abolished by the addition of both inhibitors from 50% over control to only 4%.”

May combine two claims.

HB at concentrations of 0.3-20 μM inhibited protein degradation in L6 rat skeletal myotubes dose-dependently, with activity reaching a plateau between 3 and 10 μM.

“HB at concentrations of 0.3–20 μM inhibited protein degradation dose dependently, and its activity reached a plateau between 3 and 10 μM (Fig. 2C).”

May combine two claims.

The PKC inhibitor GO6976 similarly abolished the HB anabolic response in L6 cells, while MEK1 inhibitor PD98059 and p38 MAPK inhibitor SB203580 had no effect.

“A similar effect was observed with PKC inhibitor GO6976, while MEK1 inhibitor PD98059 and p38 MAPK inhibitor SB203580 had no effect (Fig. 4).”

May combine two claims.

HB increased protein synthesis in L6 rat skeletal myotubes in a dose-dependent manner, with an EC50 of 4 μM and increases of 34.9 ± 3.1% at 10 μM and 36.9 ± 2.9% at 20 μM.

“A response approached saturation between 10 and 20 μM of HB (EC50 4 μM), with increases of 34.9 ± 3.1 and 36.9 ± 2.9%, respectively (Fig. 2A).”

May combine two claims.

HB-stimulated protein synthesis in L6 rat skeletal myotubes peaked at 3 h and started to decrease after 4 h.

“HB-stimulated protein synthesis peaked at 3 h and started to decrease after 4 h.”

May combine two claims.

HB suppression of protein degradation in L6 rat skeletal myotubes occurred time-dependently and reached a plateau at 3 h.

“Suppression of protein degradation occurred time dependently and reached a plateau at 3 h for both HB and insulin (Fig. 2D).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

Total body bone mineral content was slightly higher in HB-treated animals on normal diet, but the difference did not reach significance.

“Total body bone mineral content was slightly higher in HB-treated animals, but the difference did not reach significance.”

May combine two claims.

Control animals fed high-protein diet consumed less food and gained less weight than control animals fed normal diet.

“Indeed, control animals fed high-protein diet consumed less food and gained less weight than control animals fed normal diet (Table 1).”

May combine two claims.

Methandrostenolone produced specific binding to the rat androgen receptor with an IC50 of 24 nM and a binding curve similar to the endogenous ligand testosterone.

“Methandrostenolone produced specific binding to the androgen receptor with an IC50 of 24 nM and a binding curve similar to the endogenous ligand testosterone.”

May combine two claims. The quote only partly states this claim.

Administration of HB increased gastrocnemius muscle mass by 15.6% in HB20 and 19.0% in HB60 animals on normal diet.

“Administration of HB increased gastrocnemius muscle mass by 15.6 and 19.0% in HB20 and HB60 animals, respectively.”

The quote only partly states this claim.

Supplementation with HB had no effect on basal plasma cholesterol or triglycerides in rats on normal diet.

“Supplementation with HB had no effect on basal plasma cholesterol or triglycerides.”

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

A higher dose of HB was associated with slightly lower plasma glucose levels (4.5±0.3 mM) versus controls (5.0±0.3 mM) in rats on normal diet, but the difference did not reach statistical significance.

“A higher dose of HB was associated with slightly lower plasma glucose levels (4.5±0.3 mM) vs. controls (5.0±0.3 mM), but the difference did not reach statistical significance.”

Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

Insulin levels were slightly elevated in HB-treated rats on normal diet.

“Insulin levels were slightly elevated (Table 1).”

May combine two claims.

HB dose and time dependently stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 4 μM).

“Our findings suggest that HB dose and time dependently stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 4 μM)”

• AssumptionRests on an assumption: The L6 rat skeletal muscle cell line is a valid model for skeletal muscle anabolism in vivo.

May combine two claims.

Change in grip strength for front limbs was greater in HB-treated animals but did not reach significance.

“The change in grip strength for front limbs was also greater in HB-treated animals (Fig. 7A) but did not reach significance (0.2711±0.0660 vs. 0.1631±0.0405 kg for controls).”

May combine two claims.

Oral HB increased the weight of bulbocavernosus/levator ani muscle complex, but the change was not statistically significant.

“In contrast, HB increased the weight of bulbocavernosus/levator ani muscle complex (the skeletal muscle biomarker of anabolic activity), although the change was not statistically significant.”

May combine two claims.

Subcutaneous HB at 4 mg/kg significantly increased glans penis and bulbocavernosus/levator ani muscle complex weights in ORX rats.

“for which a significant increase was observed at 4 mg/kg HB (Table 2).”

May combine two claims.

Subcutaneous HB at 1- and 10-fold doses relative to positive control did not change androgen-sensitive tissue weights from ORX controls, except for glans penis and bulbocavernosus/levator ani muscle complex.

“When HB was injected subcutaneously at 1- and 10-fold doses relative to positive control in the Hershberger assay (testosterone propionate at 0.4 mg/kg), androgen-sensitive tissue weights did not differ from those of ORX controls with the exception of glans penis and bulbocavernosus/levator ani muscle complex”

May combine two claims.

Oral administration of HB to ORX rats increased gastrocnemius muscle mass by 13.8% and 10.3% in HB20 and HB60 animals, respectively, almost restoring muscle to original size.

“Oral administration of HB to ORX rats increased gastrocnemius muscle mass by 13.8% and 10.3% in HB20 and HB60 animals, respectively, therefore almost restoring the muscle to its original size.”

May combine two claims.

HB treatment in castrated mice prevented gastrocnemius fiber atrophy and increased median fiber area of type I and type IIa fibers above castrated control levels (P<0.001).

“HB treatment in castrated mice prevented gastrocnemius fiber atrophy and increased median fiber area of type I and type IIa fibers above castrated control levels (P<0.001).”

May combine two claims.

Oral 24-d administration of HB to healthy rats selectively increased body weight gain, lean body mass, and gastrocnemius muscle mass compared with vehicle-treated controls.

“Oral 24-d administration of HB to healthy rats selectively increased body weight gain, lean body mass, and gastrocnemius muscle mass as compared with vehicle-treated controls (Fig. 5 and Table 1).”

May combine two claims.

Neither PD98059 nor SB203580 had any measurable effect on brassinosteroid-driven modulation of protein synthesis in muscle cells.

“However, neither PD98059 (a specific inhibitor of MEK1 kinase that functions in a mitogen activated protein kinase cascade) nor SB203580 (a specific inhibitor of p38 MAP kinase homologues) had any measurable effect on brassinosteroid-driven modulation of protein synthesis in muscle cells (Fig. 4).”

May combine two claims.

HB has low or no significant binding to the androgen receptor and did not modulate plasma testosterone levels.

“The additional observation that HB has low or no significant binding to the androgen receptor and did not modulate plasma testosterone levels (Fig. 6A)”

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

Plasma triglycerides were decreased in control animals fed a high-protein diet.

“Their plasma tryglicerides were also decreased (Table 1).”

May combine two claims.

Both triciribine and LY294002 abolished the anabolic effect of brassinosteroid treatment on protein synthesis in muscle cells.

“Both treatments abolished anabolic effect of brassionosteroid treatment on protein synthesis in muscle cells.”

May combine two claims.

Control animals fed a high-protein diet exhibited decreased body weight gain, food intake, and other body composition parameters compared with control animals fed normal diet.

“As expected (42), control animals fed a high-protein diet (Fig. 5C, D) exhibited decreased body weight gain, food intake, and other body composition parameters compared with control animals fed normal diet (Fig. 5A, B).”

• cites [42] 42. Jean C., Rome S., Mathe V., Huneau J. F., Aattouri N., Fromentin G., Achagiotis C. L., Tome D. (2001) Metabolic evidence for adaptation to a high protein diet in rats. J. Nutr. 131, 91–98 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In this study, 10 d oral administration of HB to castrated animals led to substantial increases in the total number of myofibers and the cross-sectional area of oxidative type I and type IIa muscle fibers important for increased physical performance and endurance.

“In this study, we show that 10 d oral administration of HB to castrated animals led to substantial increases in the total number of myofibers and the cross-sectional area of oxidative type I and type IIa muscle fibers important for increased physical performance and endurance.”

Classified as probably not a substantial claim. May combine two claims.

Akt stimulates glucose uptake, glycogen synthesis, and protein synthesis via Akt/mTOR and Akt/GSK-3β signaling networks and inhibits apoptosis and protein degradation in skeletal muscle by inactivating FoxO transcription factors.

“Akt stimulates glucose uptake, glycogen synthesis, and protein synthesis via Akt/mTOR and Akt/GSK-3β signaling networks (14) and inhibits apoptosis and protein degradation in skeletal muscle by inactivating FoxO transcription factors (15).”

• Also stated in: § DISCUSSION · plain

  “Akt stimulates glucose uptake, glycogen synthesis, and protein synthesis via Akt/mTOR and Akt/GSK-3β signaling networks (14) and inhibits apoptosis and protein degradation in skeletal muscle by inactivating FoxO transcription factors (15).”

• cites [14] 14. Rommel C., Bodine S. C., Clarke B. A., Rossman R., Nunez L., Stitt T. N., Yancopoulos G. D., Glass D. J. (2001) Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat. Cell Biol. 3, 1009–1013 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [15] 15. Stitt T. N., Drujan D., Clarke B. A., Panaro F., Timofeyva Y., Kline W. O., Gonzalez M., Yancopoulos G. D., Glass D. J. (2004) The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol. Cell. 14, 395–403 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

  Not checked in the free run.

May combine two claims.

24-Epibrassinolide has a favorable safety profile; its median lethal dose is >1000 mg/kg in mice and >2000 mg/kg in rats when applied orally or subcutaneously.

“24-Epibrassinolide, the most widely used brassinosteroid in agriculture, has a favorable safety profile. The median lethal dose (LD50) of this compound is >1000 mg/kg in mice and >2000 mg/kg in rats when applied orally or subcutaneously (23).”

• cites [23] 23. Kuzmitsky B. B., Mizulo N. A. (1991) Study of acute toxicity of epibrassinolide and its preparative forms. Technical Report, pp. 1–44, Academy of Sciences of Belarus, Minsk [Google Scholar]Not checked yet

  Not checked in the free run.

May combine two claims.

HB-stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells are mediated in part by the PI3K/Akt signaling pathway.

“28-Homobrassinolide (HB), a steroidal lactone with potent plant growth-promoting property, stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 4 μM) mediated in part by PI3K/Akt signaling pathway.”

May combine two claims.

Oral application of HB triggers a selective anabolic response with minimal or no androgenic side-effects in mammals.

“These findings suggest that oral application of HB triggers selective anabolic response with minimal or no androgenic side-effects”

• AssumptionRests on an assumption: Oral HB is bioavailable and reaches skeletal muscle in rats at the doses used.

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

Akt is a serine/threonine kinase that signals downstream of growth factor receptors and PI3K; growth factor receptors, nutrients, and muscle contraction increase Akt activity.

“Akt is a serine/threonine kinase that signals downstream of growth factor receptors and phosphoinositide-3 kinase (PI3K); therefore, growth factor receptors, nutrients, and even muscle contraction increase Akt activity (13).”

• cites [13] 13. Frost R. A., Lang C. H. (2007) Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass. J. Appl. Physiol. 103, 378–387 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

Total testosterone in plasma samples was quantified by ELISA with assay sensitivity 0.066 ng/ml, intra-assay and interassay coefficients of variation 6.5-11.1 and 9.3-11.3%, and accuracy 84-123%.

“Total testosterone in plasma samples was quantified by ELISA assay (DRG Diagnostics, Marburg, Germany; assay sensitivity, 0.066 ng/ml; intra-assay and interassay coefficients of variation, 6.5–11.1 and 9.3–11.3%, respectively; accuracy, 84–123%).”

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

Plasma insulin was determined by rat/mouse insulin ELISA with assay sensitivity 0.2 ng/ml, intra-assay and interassay coefficients of variation 0.9-8.4 and 6.0-17.9%, and accuracy 83-102%.

“Plasma concentrations of insulin were determined by rat/mouse insulin ELISA kit (Millipore, Billerica, MA, USA; assay sensitivity, 0.2 ng/ml; intra-assay and interassay coefficients of variation, 0.9–8.4 and 6.0–17.9%, respectively; accuracy 83–102%).”

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

All animal experiments were performed according to procedures approved by the Rutgers Institutional Animal Care and Use Committee in an Association for Assessment and Accreditation of Laboratory Animal Care accredited animal care facility.

“All animal experiments were performed according to procedures approved by the Rutgers Institutional Animal Care and Use Committee in an Association for Assessment and Accreditation of Laboratory Animal Care accredited animal care facility.”

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

Animals were randomly distributed into groups according to body weight 1 d before dosing.

“Animals were randomly distributed into groups according to body weight 1 d before dosing.”

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

Plasma triglycerides and total cholesterol were measured by enzymatic colorimetric assays with intra-assay and interassay coefficients of variation of 9-10%.

“Plasma triglycerides and total cholesterol were measured by enzymatic colorimetric assays (Wako Diagnostics, Richmond, VA, USA; intra-assay and interassay coefficients of variation, 9–10%).”

Classified as probably not a substantial claim. May combine two claims.

DEXA quality control was performed daily; the coefficient of variation for total body, lean mass, and bone mineral content was 1.93, 3.43, and 2.10%, respectively, as measured in 5 rats scanned 3 times each.

“Quality control was performed daily. The coefficient of variation for total body, lean mass, and bone mineral content was 1.93, 3.43, and 2.10%, respectively, as measured in 5 rats scanned 3 times each.”

May combine two claims.

HB activated total protein synthesis, induced de novo polypeptide synthesis, and increased thermotolerance of total protein synthesis in plants subjected to heat shock.

“In addition, HB activated total protein synthesis, induced de novo polypeptide synthesis, and increased thermotolerance of total protein synthesis in plants subjected to heat shock (30).”

• cites [30] 30. Kulaeva O. N., Burkhanova E. A., Fedina A. B., Khokhlova V. A., Bokebayeva G. A., Vorbrodt H. M., Adam G. N. (2009) Effect of brassinosteroids on protein synthesis and plant-cell ultrastructure under stress conditions. In Brassinosteroids pp. 141–155, American Chemical Society, Washington, D.C., USA [Google Scholar]Not checked yet

  Not checked in the free run.

May combine two claims.

The effective HB concentrations that produced Akt activation were comparable with the concentration required to modulate protein synthesis, suggesting that HB involves Akt activation in the stimulation of protein synthesis and suppression of protein degradation.

“The effective HB concentrations that produced Akt activation were comparable with the concentration required to modulate protein synthesis, suggesting that HB involves Akt activation in the stimulation of protein synthesis and suppression of protein degradation.”

May combine two claims.

Oral application of HB triggers an anabolic response with minimal or no androgenic side effects.

“Moreover, our data demonstrate that oral application of HB triggers an anabolic response with minimal or no androgenic side effects.”

May combine two claims.

Although HB produced anabolic effects in animals similar to androgens, they seemed to be pharmacologically different, as HB administration produced only minimal androgenic side effects, in sharp contrast to powerful androgenic effects of anabolic steroids.

“Although HB produced anabolic effects in animals similar to androgens, they seemed to be pharmacologically different, as HB administration (oral or subcutaneous) produced only minimal androgenic side effects, in sharp contrast to powerful androgenic effects of anabolic steroids.”

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

Animal steroid hormones act through the nuclear receptor family of transcription factors, while plant brassinosteroids signal through a cell surface receptor kinase-mediated signal transduction pathway.

“While animal steroid hormones act through nuclear receptor family of transcription factors, plant brassinosteroids signal through a cell surface receptor kinase-mediated signal transduction pathway (8, 9).”

• cites [8] 8. Wang Z. Y., Seto H., Fujioka S., Yoshida S., Chory J. (2001) BRI1 is a critical component of a plasma-membrane receptor for plant steroids. Nature 410, 380–383 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [9] 9. Nam K. H., Li J. (2002) BRI1/BAK1, a receptor kinase pair mediating brassinosteroid signaling. Cell 110, 203–212 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Major structural differences between HB and androgens, including the lactone function at C6/C7, the 2 hydroxyls at C2 and C3, and the methyl substitution at C24, may restrict HB from activating the nuclear androgen receptor and explain the difference in pharmacological responses.

“These chemical differences may restrict HB from activating the nuclear androgen receptor and explain the difference in pharmacological responses.”

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

Brassinosteroids are present in small quantities in foods and plants.

“Brassinosteroids are present in small quantities in foods and plants (1).”

• cites [1] 1. Bajguz A., Tretyn A. (2003) The chemical characteristic and distribution of brassinosteroids in plants. Phytochemistry 62, 1027–1046 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

  Not checked in the free run.

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

In plants, brassinosteroids play an essential role in plant growth and development, as well as thermotolerance.

“In plants, brassinosteroids play an essential role in plant growth and development (4–7), as well as thermotolerance (30).”

• cites [4] 4. Clouse S. D., Sasse J. M. (1998) Brassinosteroids: essential regulators of plant growth and development. Annu. Rev. Plant Physiol. Plant Mol. Biol. 49, 427–451 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [5] 5. Losel R., Wehling M. (2003) Nongenomic actions of steroid hormones. Nat. Rev. Mol. Cell. Biol. 4, 46–56 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [6] 6. Clouse S. D. Brassinosteroids. Plant counterparts to animal steroid hormones? (2002) Vitam. Horm. 65, 195–223 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [7] 7. Mussig C. (2005) Brassinosteroid-promoted growth. Plant Biol. (Stuttg.) 7, 110–117 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [30] 30. Kulaeva O. N., Burkhanova E. A., Fedina A. B., Khokhlova V. A., Bokebayeva G. A., Vorbrodt H. M., Adam G. N. (2009) Effect of brassinosteroids on protein synthesis and plant-cell ultrastructure under stress conditions. In Brassinosteroids pp. 141–155, American Chemical Society, Washington, D.C., USA [Google Scholar]Not checked yet

  Not checked in the free run.

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

Brassinosteroids share some similarities with ecdysteroids that have a wide array of physiological and pharmacological effects in animals and insects, including modulation of protein synthesis and carbohydrate metabolism.

“At the same time, brassinosteroids share some similarities with ecdysteroids (Fig. 1C) that have a wide array of physiological and pharmacological effects in animals and insects (46), including modulation of protein synthesis (47) and carbohydrate metabolism (48).”

• cites [46] 46. Bathori M., Toth N., Hunyadi A., Marki A., Zador E. (2008) Phytoecdysteroids and anabolic-androgenic steroids–structure and effects on humans. Curr. Med. Chem. 15, 75–91 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [47] 47. Gorelick-Feldman J., Maclean D., Ilic N., Poulev A., Lila M. A., Cheng D., Raskin I. (2008) Phytoecdysteroids increase protein synthesis in skeletal muscle cells. J. Agric. Food Chem. 56, 3532–3537 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [48] 48. Kizelsztein P., Govorko D., Komarnytsky S., Evans A., Wang Z., Cefalu W. T., Raskin I. (2009) 20-Hydroxyecdysone decreases weight and hyperglycemia in a diet-induced obesity mice model. Am. J. Physiol. Endocrinol. Metab. 296, E433–E439 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceNot checked yet

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

Classical mammalian steroid hormones either inhibit or induce apoptosis in a concentration- or tissue-specific manner.

“This effect is similar to classical mammalian steroid hormones that either inhibit or induce apoptosis in the concentration- or tissue-specific manner (59).”

• cites [59] 59. Pushkala K., Gupta P. D. (2001) Steroid hormones regulate programmed cell death: a review. Cytobios 106, 201–217 [PubMed] [Google Scholar] Articles from The FASEB Journal are provided here courtesy of The Federation of American Societies for Experimental BiologyNot checked yet

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

Akt is a serine/threonine kinase that signals downstream of growth factor receptors and phosphoinositide-3 kinase PI3K.

“Akt is a serine/threonine kinase that signals downstream of growth factor receptors and phosphoinositide-3 kinase PI3K.”

• cites [13] 13. Frost R. A., Lang C. H. (2007) Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass. J. Appl. Physiol. 103, 378–387 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Brassinosteroids caused cell cycle arrest and apoptosis of human breast cancer cells when tested at doses >30 μM, without affecting the normal nontumor cell growth of BJ fibroblasts.

“At the same time, brassinosteroids caused cell cycle arrest and apoptosis of human breast cancer cells when tested at doses >30 μM, without affecting the normal nontumor cell growth of BJ fibroblasts (22).”

• cites [22] 22. Malikova J., Swaczynova J., Kolar Z., Strnad M. (2008) Anticancer and antiproliferative activity of natural brassinosteroids. Phytochemistry 69, 418–426 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

  Not checked in the free run.

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

GSK-3β controls cell survival through regulation of β-catenin, and inhibition of Akt suppresses the Wnt pathway by activation of GSK-3β and degradation of β-catenin.

“At the same time, GSK-3β also controls cell survival through regulation of β-catenin, 1 of the key molecules in Wnt signaling (11), and inhibition of Akt suppresses the Wnt pathway by activation of GSK-3β and degradation of ß-catenin (51).”

• cites [11] 11. Tolwinski N. S., Wieschaus E. (2004) Rethinking WNT signaling. Trends Genet. 20, 177–181 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [51] 51. Naito A. T., Akazawa H., Takano H., Minamino T., Nagai T., Aburatani H., Komuro I. (2005) Phosphatidylinositol 3-kinase-Akt pathway plays a critical role in early cardiomyogenesis by regulating canonical Wnt signaling. Circ. Res. 97, 144–151 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

  Not checked in the free run.

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

Both FOXO3a and GSK-3β modulate transcription of androgen receptor; FOXO3a promotes transcriptional activity of AR, while GSK-3β acts as its inhibitor.

“Moreover, both FOXO3a and GSK-3β modulate transcription of androgen receptor (AR); while the former promotes transcriptional activity of AR (49), the latter acts as its inhibitor (50).”

• cites [49] 49. Yang L., Xie S., Jamaluddin M. S., Altuwaijri S., Ni J., Kim E., Chen Y. T., Hu Y. C., Wang L., Chuang K. H., Wu C. T., Chang C. (2005) Induction of androgen receptor expression by phosphatidylinositol 3-kinase/Akt downstream substrate, FOXO3a, and their roles in apoptosis of LNCaP prostate cancer cells. J. Biol. Chem. 280, 33558–33565 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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• cites [50] 50. Salas T. R., Kim J., Vakar-Lopez F., Sabichi A. L., Troncoso P., Jenster G., Kikuchi A., Chen S. Y., Shemshedini L., Suraokar M., Logothetis C. J., DiGiovanni J., Lippman S. M., Menter D. G. (2004) Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity. J. Biol. Chem. 279, 19191–19200 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

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

Skeletal muscle shows plasticity and can undergo conversion between different fiber types in response to exercise training, modulation of motoneuron activity, or castration.

“Skeletal muscle shows plasticity and can undergo conversion between different fiber types in response to exercise training, modulation of motoneuron activity, or castration (55).”

• cites [55] 55. Layman D. K., Boileau R. A., Erickson D. J., Painter J. E., Shiue H., Sather C., Christou D. D. (2003) A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women. J. Nutr. 133, 411–417 [DOI] [PubMed] [Google Scholar] sourceNot checked yet

  Not checked in the free run.

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

Brassinosteroid signaling in plants resembles the Wnt pathway and is mediated by GSK3-like kinase.

“Curiously, brassinosteroid signaling in plants resembles the Wnt pathway and is mediated by GSK3-like kinase (10).”

• cites [10] 10. Kim T. W., Guan S., Sun Y., Deng Z., Tang W., Shang J. X., Burlingame A. L., Wang Z. Y. (2009) Brassinosteroid signal transduction from cell-surface receptor kinases to nuclear transcription factors. Nat. Cell Biol. 11, 1254–1260 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceNot checked yet

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