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We examined whether vitamin A improved mucosal immune depression in mice with wasting protein deficiency. In male C3H/HeN mice fed a semi-purified 1% protein diet for 2 wk, plasma retinol and immunoglobulin A (IgA) concentrations in the small intestinal mucosa were 50 and 55%, respectively, of those in mice fed a semi-purified 20% protein diet, (P < 0.05). Daily supplementation of 0.3 mg of retinyl acetate to protein-deficient mice for 2 wk increased the plasma retinol level to the value in the protein-sufficient mice. However, 1 mg/d of retinyl acetate was required to prevent the decline of the IgA level caused by the protein deficiency. Mice fed the low-protein diet had lower concentrations of IL-4 and IL-5 in the small intestinal mucosa and fewer IL-4- and IL-5-containing cells in the lamina propria (P < 0. 05). Retinyl acetate (1 mg) significantly restored the IL-5 level and the number of IL-4- and IL-5-containing cells. After immunization with 20 microg of cholera toxin (CT), the intestinal mucosa of protein-deficient mice contained significantly less CT-specific IgA than control mice. Treatment with 1 mg of retinyl acetate prevented the decline of anti-CT IgA level in the protein-deficient mice, improving their survival rate after an exposure to 0.1 mg of CT. These results suggest that large oral supplements of vitamin A may preserve mucosal IgA level during protein malnutrition, possibly by stimulating Th2 cytokine production and thereby, inducing resistance against infection. [ABSTRACT FROM AUTHOR]

The aim of this study was to reveal the role of intracellular glutathione in the oxidative stress responses of gastric epithelial cells. Metabolic radiolabeling with L-[35S]methionine and analysis of synthesized proteins by gel electrophoresis and fluorography showed that upon exposure to hydrogen peroxide (H2O2) or diamide, primary cultures of guinea-pig gastric epithelial cells rapidly induced several undefined proteins, as well as heat shock proteins. When intracellular glutathione was depleted to less than 10% of the control value by treatment with buthionine-[S,R]-sulfoximine, these inductions were completely inhibited. Gel mobility shift assay demonstrated that H2O2 and diamide rapidly activated nuclear factor-kappa B (NF-kappaB), and diamide activated activator protein (AP)-1, and c-Jun/activating transcription factor (ATF)-2, suggesting that the response may be coupled to these reduction-oxidation (redox)-sensitive transcription factors, as well as heat shock transcription factor 1. The activations of NF-kappaB, AP-1, and c-Jun/ATF-2 by the oxidants did not occur in glutathione-depleted cells. Northern blot analysis showed that glutathione depletion markedly or completely suppressed the diamide-induced expression of c-fos and c-jun mRNAs. These results suggest that intracellular glutathione redox may participate in the initiation of oxidative stress responses; thereby, it plays an important role in gastric mucosal defense. [ABSTRACT FROM AUTHOR]

The aim of this study was to reveal oxidant-sensitive components in gastric epithelial cells, which may regulate inflammatory processes in gastric mucosa. Gel mobility shift assay showed that treatment of cultured guinea pig gastric epithelial cells with hydrogen peroxide or diamide produced a KB oligonucleotide-protein complex within 5 min. The binding proteins consisted of a p50/p65 heterodimer, which was identified by immunosupershift, UV cross-linking, and immunoprecipitation analyses. Immunocytochemical study demonstrated that surface epithelial cells and parietal cells expressed p500 and p65 mainly in the cytosol, and the oxidants rapidly initiated the nuclear translocation of the components. The oxidants caused the up-regulation of p105 (a p50 precursor) synthesis and the expression of inducible nitric oxide synthase mRNA. These results suggest that the oxidant-sensitive p50/p65 heterodimer in gastric epithelial cells may play an important role in transcriptional activation of genes involved in inflammatory responses of the stomach. [ABSTRACT FROM AUTHOR]

Vitamin A is a potent inducer for liver/bone/kidney alkaline phosphatase (L/B/K ALP) in a variety of tissues. However, the evidence for induction of L/B/K ALP by vitamin A in small intestine is limited. In this study, we investigated the influence of vitamin A on L/B/K ALP expression in rat small intestinal crypt IEC-6 cells and fetal rat small intestine. Treatment of IEC-6 cells with all-trans retinoic acid (RA) increased the levels of activity, protein and mRNA of L/B/K ALP, whereas enterocyte-specific proteins, including intestinal ALP, sucrase-isomaltase and glucose transporter-2, were not induced. The reverse transcription-polymerase chain reaction technique revealed that this L/B/K ALP transcript had the bone-type but not the liver-type leader exon. IEC-6 cells constitutively expressed mRNAs of all subtypes of retinoic acid receptor (RAR) and retinoid X receptor (RXR) at varied concentrations. Among these receptor mRNAs, RARbeta mRNA quickly responded to RA treatment, and the level was doubled within 4 h. Gel mobility shift assay showed that RA induced an RXRE-binding activity in IEC-6 cells. The L/B/K ALP transcript, expressed in fetal rat small intestine, also contained the bone-type leader exon. Intragastric administration of 10 mg retinyl acetate to pregnant rats from gestational d 7 to 15 increased the levels of this transcript and enzyme in 15-d fetal rat small intestine. Our results suggest that vitamin A may be an important regulator for L/B/K ALP expression in fetal rat small intestine as well as in IEC-6 cells. [ABSTRACT FROM AUTHOR]

The DOPA-decarboxylase (DDC) gene is crucial for dopamine synthesis and influences various biological functions in insects, including body coloration, behavior, learning, and sleep. However, its evolutionary impact remains largely unexplored. This study reports on the tandem duplication of two bona fide ddc genes (ddc1 and ddc2) in the Gryllidae cricket family. We herein investigated the function of ddc1 and ddc2 using Gryllus bimaculatus (Gb) as a model. Our results revealed that Gb'ddc1 was expressed systemically, with its expression being higher immediately after molting compared to the stage following melanin pigmentation. In homozygous knockout mutants of Gb'ddc1, generated via CRISPR/Cas9, reduced body color pigmentation and had translucent cuticles, decreased dopamine levels, and over-accumulated DOPA. These mutants died shortly after hatching, likely due to cuticle defects, underscoring the essential role of dopamine, produced by Gb'ddc1, in melanin synthesis. Conversely, Gb'ddc2 expression was confined to the ovary and was not up-regulated after molting. Homozygous knockout mutants of Gb'ddc2 exhibited no body color defects, whereas hatchability and embryonic development rates were significantly reduced. Interestingly, dopamine levels in the ovaries were significantly elevated in Gb'ddc2 mutants. This suggests that normal ovarian dopamine levels, modulated by Gb'ddc2, are vital for fertility maintenance. The function of Gb'ddc2 differs from that of typical ddc, indicating neofunctionalization through evolutionary duplication. Overall, Gb'ddc1 and Gb'ddc2 have distinct functions, and precise regulation of ovarian dopamine levels using these two ddc genes may have enhanced cricket fertility., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

3-(4-Hydroxy-3-methoxyphenyl) propionic acid is an in vivo metabolite of 4-hydroxy-3-methoxycinnamic acid which is abundantly found in coffee bean, rice bran, fruits, and vegetables. Previous studies reported that polyphenols and their metabolites exhibit positive effects on muscle health. Thus, the effect of 3-(4-hydroxy-3-methoxyphenyl) propionic acid on muscle atrophy induced by dexamethasone was investigated using mouse C2C12 skeletal myotubes. Dexamethasone treatment (10 ‍μM) reduced the diameter and myosin heavy chain protein expression in C2C12 myotubes; it also increased muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/Atrogin-1 and muscle ring finger protein-1, along with their upstream regulator Krüppel-like factor 15. Dexamethasone dephosphorylated FoxO3a transcription factor and increased total FoxO3a expression. Interestingly, 10 ‍μM 3-(4-hydroxy-3-methoxyphenyl) propionic acid treatment significantly attenuated dexamethasone-induced reduction in myotube thickness and muscle protein degradation and suppressed muscle atrophy-associated ubiquitin ligases. 3-(4-Hydroxy-3-methoxyphenyl) propionic acid also prevented dexamethasone-induced Krüppel-like factor 15 and FoxO3a expression. In conclusion, these results suggest that in vivo metabolite of polyphenols per se could be the real origin of the anti-muscular atrophy activity, as 3-(4-hydroxy-3-methoxyphenyl) propionic acid ameliorated glucocorticoid-induced muscle atrophy by suppressing Atrogin-1 and MuRF-1., Competing Interests: HKayaki, YN, SY, and HKuwahara are employed in Maruzen Pharmaceuticals Co., Ltd. All other authors have no conflicts of interest., (Copyright © 2025 JCBN.)

Myogenesis is regulated mainly by transcription factors known as Myogenic Regulatory Factors (MRFs), and the transcription is affected by epigenetic modifications. However, the epigenetic regulation of myogenesis is poorly understood. Here, we focused on the epigenomic modification enzyme, PHF2, which demethylates histone 3 lysine 9 dimethyl (H3K9me2) during myogenesis. Phf2 mRNA was expressed during myogenesis, and PHF2 was localized in the nuclei of myoblasts and myotubes. We generated Phf2 knockout C2C12 myoblasts using the CRISPR/Cas9 system and analyzed global transcriptional changes via RNA-sequencing. Phf2 knockout (KO) cells 2 d post differentiation were subjected to RNA sequencing. Gene ontology (GO) analysis revealed that Phf2 KO impaired the expression of the genes related to skeletal muscle fiber formation and muscle cell development. The expression levels of sarcomeric genes such as Myhs and Mybpc2 were severely reduced in Phf2 KO cells at 7 d post differentiation, and H3K9me2 modification of Mybpc2, Mef2c and Myh7 was increased in Phf2 KO cells at 4 d post differentiation. These findings suggest that PHF2 regulates sarcomeric gene expression via epigenetic modification., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fukushima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study investigated the protective effect of carnosine and its components (L-histidine and β-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Myotubes were treated with Dex (10 μM) to induce muscle atrophy manifested by decreased myotube diameter, low myosin heavy chain content, and increased expression of muscle atrophy-associated ubiquitin ligases (Atrogin-1, MuRF-1, and Cbl-b). Carnosine (20 mM) treatment significantly improved the myotube diameter and MyHC protein expression level in Dex-treated C2C12 myotubes. It also downregulated the expression of Atrogin-1, MuRF-1, and Cbl-b and suppressed the expression of forkhead box O3 (FoxO3a) mediated by Dex. Furthermore, reactive oxygen species production was increased by Dex but was ameliorated by carnosine treatment. However, HA (20 mM), the component of carnosine, treatment was found ineffective in preventing Dex-induced protein damage. Therefore, based on above results it can be suggested that carnosine could be a potential therapeutic agent to prevent Dex-induced muscle atrophy compared to its components HA.

Skeletal muscle atrophy and the inhibition of muscle regeneration are known to occur as a natural consequence of aging, yet the underlying mechanisms that lead to these processes in atrophic myofibers remain largely unclear. Our research has revealed that the maintenance of proper mitochondrial-associated endoplasmic reticulum membranes (MAM) is vital for preventing skeletal muscle atrophy in microgravity environments. We discovered that the deletion of the mitochondrial fusion protein Mitofusin2 (MFN2), which serves as a tether for MAM, in human induced pluripotent stem (iPS) cells or the reduction of MAM in differentiated myotubes caused by microgravity interfered with myogenic differentiation process and an increased susceptibility to muscle atrophy, as well as the activation of the Notch signaling pathway. The atrophic phenotype of differentiated myotubes in microgravity and the regenerative capacity of Mfn2-deficient muscle stem cells in dystrophic mice were both ameliorated by treatment with the gamma-secretase inhibitor DAPT. Our findings demonstrate how the orchestration of mitochondrial morphology in differentiated myotubes and regenerating muscle stem cells plays a crucial role in regulating Notch signaling through the interaction of MAM., Competing Interests: YI, MY, TY, KH, TN, TS No competing interests declared, (© 2023, Ito, Yamagata et al.)

Insect body colors and patterns change markedly during development in some species as they adapt to their surroundings. The contribution of melanin and sclerotin pigments, both of which are synthesized from dopamine, to cuticle tanning has been well studied. Nevertheless, little is known about how insects alter their body color patterns. To investigate this mechanism, the cricket Gryllus bimaculatus, whose body color patterns change during postembryonic development, was used as a model in this study. We focused on the ebony and tan genes, which encode enzymes that catalyze the synthesis and degradation, respectively, of the precursor of yellow sclerotin N-β-alanyl dopamine (NBAD). Expression of the G. bimaculatus (Gb) ebony and tan transcripts tended to be elevated just after hatching and the molting period. We found that dynamic alterations in the combined expression levels of Gb'ebony and Gb'tan correlated with the body color transition from the nymphal stages to the adult. The body color of Gb'ebony knockout mutants generated by CRISPR/Cas9 systemically darkened. Meanwhile, Gb'tan knockout mutants displayed a yellow color in certain areas and stages. The phenotypes of the Gb'ebony and Gb'tan mutants probably result from an over-production of melanin and yellow sclerotin NBAD, respectively. Overall, stage-specific body color patterns in the postembryonic stages of the cricket are governed by the combinatorial expression of Gb'ebony and Gb'tan. Our findings provide insights into the mechanism by which insects evolve adaptive body coloration at each developmental stage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Inoue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in cell membranes and mitochondria, which consist of the bilayer molecules. Targeting mitochondria to ameliorate inflammatory diseases by regulating mitochondrial metabolism has become possible and topical. Although AX has been shown to have anti-inflammatory effects in various cells, the mechanisms are quite different. In particular, the role of AX on mitochondrial metabolism in macrophages is still unknown. In this study, we investigated the effect of AX on mitochondria-mediated inflammation and its mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. AX attenuated the mitochondrial O 2 - production and maintained the mitochondrial membrane potential, implying that AX preserved mitochondrial homeostasis to avoid LPS stimulation-induced mitochondrial dysfunction. Additionally, AX prevented the decrease in mitochondrial complexes I, II, and III, which were caused by LPS stimulation. Especially, AX inhibited the reduction in mitochondrial succinate dehydrogenase (SDH; complex II) activity and upregulated the protein and mRNA level of SDH complex, subunit B. Furthermore, AX blocked the IL-1β expression by regulating the SDH-HIF-1α axis and suppressed the energy shift from an OXPHOS phenotype to a glycolysis phenotype. These findings revealed important effects of AX on mitochondrial enzymes as well as on mitochondrial energy metabolism in the immune response. In addition, these raised the possibility that AX plays an important role in other diseases caused by SDH mutation and metabolic disorders., Competing Interests: The authors declare that there is no conflict of interest.

This study investigated the effect of morin, a flavonoid, on dexamethasone-induced muscle atrophy in C57BL/6J female mice. Dexamethasone (10 mg/kg body weight) for 10 days significantly reduced body weight, gastrocnemius and tibialis anterior muscle mass, and muscle protein in mice. Dexamethasone significantly upregulated muscle atrophy-associated ubiquitin ligases, including atrogin-1 and MuRF-1, and the upstream transcription factors FoxO3a and Klf15. Additionally, dexamethasone significantly induced the expression of oxidative stress-sensitive ubiquitin ligase Cbl-b and the accumulation of the oxidative stress markers malondialdehyde and advanced protein oxidation products in both the plasma and skeletal muscle samples. Intriguingly, morin treatment (20 mg/kg body weight) for 17 days effectively attenuated the loss of muscle mass and muscle protein and suppressed the expression of ubiquitin ligases while reducing the expression of upstream transcriptional factors. Therefore, morin might act as a potential therapeutic agent to attenuate muscle atrophy by modulating atrophy-inducing genes and preventing oxidative stress., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Processed aconite root (PA), the tuberous root of Aconitum carmichaelii prepared by autoclaving, is a crude drug used in Japanese traditional Kampo medicine and traditional Chinese medicine for the symptoms of kidney deficiency, that is related to the muscle atrophy in modern medicine. The objective of the present study is to evaluate the effectiveness of PA on muscle atrophy and to find its active ingredients using dexamethasone-induced muscle ring finger protein-1 (MuRF1) mRNA expression in murine myoblast C2C12 cells. Dexamethasone-induced MuRF1 expression was significantly suppressed by methanol-soluble part of boiling water extract of PA in a concentration-dependent manner with its IC 50 value of 1.5 mg/ml. By the activity-guided fractionations of PA extract using the partition between organic solvents and its aqueous solution, the activity of PA did not transfer into the fraction containing aconitine-type diterpenoid alkaloids but into BuOH layer. Then, we found higenamine and salsolinol as the active ingredients in PA. Higenamine and salsolinol significantly suppressed dexamethasone-induced MuRF1 expression, and their IC 50 values were 0.49 and 50 µM, respectively. The contents of higenamine and salsolinol in the decoctions of commercially available fourteen PA products are 0.12 and 14 µg/ml as the average values, and varied with the coefficient of variation (CV) values of 97 and 63%, respectively. Higenamine also significantly suppressed dexamethasone-induced mRNA expressions of muscle atrophy F-box protein (MAFbx)/atrogin1, casitas B-lineage lymphoma-b (Cbl-b), troponin, branched-chain amino acid aminotransferase 2 (BCAT2), and Bcl-2 binding and pro-apoptotic protein3 (Bnip3). Although the quality control of PA is regulated by the contents of diterpene alkaloids, salsolinol and higenamine can be used as the marker compounds to certificate the pharmacological activities of PA., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Balenine is one of the endogenous imidazole dipeptides derived from marine products. It is composed of beta-alanine and 3-methyl-L-histidine, which exist mainly in the muscles of marine organisms. The physiological functions of dietary balenine are not well-known. In this study, we investigated whether the supplementation of dietary balenine was associated with muscle function in a cardiotoxin-indued muscle degeneration/regeneration model. Through morphological observation, we found that the supplementation of balenine-enriched extract promoted the regeneration stage. In addition, the expression of regeneration-related myogenic marker genes, such as paired box protein 7, MyoD1, myogenin, and Myh3, in a group of mice fed a balenine-enriched extract diet was higher than that in a group fed a normal diet. Moreover, the supplementation of balenine-enriched extract promoted the expression of anti-inflammatory cytokines as well as pro-inflammatory cytokines at the degeneration stage. Interestingly, phagocytic activity in the balenine group was significantly higher than that in the control group in vitro. These results suggest that balenine may promote the progress of muscle regeneration by increasing the phagocytic activity of macrophages.

Recent studies show that muscle mass and metabolic function are interlinked. Muscle RING finger 1 (MuRF1) is a critical muscle-specific ubiquitin ligase associated with muscle atrophy. Yet, the molecular target of MuRF1 in atrophy and aging remains unclear. We examined the role of MuRF1 in aging, using MuRF1-deficient (MuRF1 -/- ) mice in vivo, and MuRF1-overexpressing cell in vitro. MuRF1 deficiency partially prevents age-induced skeletal muscle loss in mice. Interestingly, body weight and fat mass of more than 7-month-old MuRF1 -/- mice were lower than in MuRF1 +/+ mice. Serum and muscle metabolic parameters and results of indirect calorimetry suggest significantly higher energy expenditure and enhanced lipid metabolism in 3-month-old MuRF1 -/- mice than in MuRF1 +/+ mice, resulting in suppressed adipose tissue gain during aging. Pyruvate dehydrogenase kinase 4 (PDK4) is crucial for a switch from glucose to lipid metabolism, and the interaction between MuRF1 and PDK4 was examined. PDK4 protein levels were elevated in mitochondria from the skeletal muscle in MuRF1 -/- mice. In vitro, MuRF1 interacted with PDK4 but did not induce degradation through ubiquitination. Instead, SUMO posttranscriptional modification (SUMOylation) of PDK4 was detected in MuRF1-overexpressing cells, in contrast to cells without the RING domain of MuRF1. MuRF1 deficiency enhances lipid metabolism possibly by upregulating PDK4 localization into mitochondrial through prevention of SUMOylation. Inhibition of MuRF1-mediated PDK4 SUMOylation is a potential therapeutic target for age-related dysfunction of lipid metabolism and muscle atrophy., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response in differentiating leukemic blasts. The downstream transcriptional factor of PERK, a major arm of unfolded protein response, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of GADD34 gene via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in skeletal muscle. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p-38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in C2C12 cells changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation, which changes muscle fiber type., (© 2022 Adachi et al.)

Various dietary protein supplements are used by the elderly and bedridden to maintain their skeletal muscle mass and functions. High-quality proteins act as an anabolic driver and help to improve muscle strength and performance. Previously, we reported that soy protein significantly attenuates denervation-induced loss of muscle mass and myofiber cross sectional area in mice with inhibition of ubiquitination and degradation of IRS-1 in tibialis anterior muscle. It also increased muscle volume and strength in bedridden patients. In the present study, we investigated the effects of dietary soybean supplementation on muscle functions in taxi drivers lacking vigorous physical exercise. We conducted a case-control study on 25 healthy, male taxi drivers between the ages of 36 and 71 y performing minimal physical exercise. They were divided into two dietary groups: the soybean diet group (n=13) who ate daily meals (dinner) supplemented with 50 g of steamed soybean for 30 d and the control diet group (n=12) who received no soybean supplement. Next, we measured the muscle cross-sectional area (CSA) and muscle strength and function in both the groups before and after 30 d of soybean intake. The body weights of both diet groups did not differ significantly over time. However, after 30 d of soybean supplementation, the soybean-fed group developed significantly higher muscle CSA and grip strength compared to the control groups. In conclusion, dietary soybean supplementation improved muscle function in taxi drivers who lacked exercise.

Two novel reagents, N-myristoylated Cbl-b inhibitory peptide (C14-Cblin) and celastrol, a quinone methide triterpene, are reported to be effective in preventing myotube atrophy. The combined effects of C14-Cblin and celastrol on rat L6 myotubes atrophy induced by 3D-clinorotation, a simulated microgravity model, was investigated in the present study. We first examined their effects on expression in atrogenes. Increase in MAFbx1/atrogin-1 and MuRF-1 by 3D-clinorotation was significantly suppressed by treatment with C14-Cblin or celastrol, but there was no additive effect of simultaneous treatment. However, celastrol significantly suppressed the upregulation of Cbl-b and HSP70 by 3D-clinorotation. Whereas 3D-clinorotation decreased the protein level of IRS-1 in L6 myotubes, C14-Cblin and celastrol inhibited the degradation of IRS-1. C14-Cblin and celastrol promoted the phosphorylation of FOXO3a even in microgravity condition. Simultaneous administration of C14-Cblin and celastrol had shown little additive effect in reversing the impairment of IGF-1 signaling by 3D-clinorotation. While 3D-clinorotation-induced marked oxidative stress in L6 myotubes, celastrol suppressed 3D-clinorotation-induced ROS production. Finally, the C14-Cblin and celastrol-treated groups were inhibited decrease in L6 myotube diameter and increased the protein content of slow-twitch MyHC cultured under 3D-clinorotation. The simultaneous treatment of C14-Cblin and celastrol additively prevented 3D-clinorotation-induced myotube atrophy than single treatment. J. Med. Invest. 69 : 127-134, February, 2022.

We previously reported that intramuscular injections of ubiquitin ligase CBLB inhibitory pentapeptide (Cblin; Asp-Gly-pTyr-Met-Pro) restored lost muscle mass caused by sciatic denervation. Here, we detected Cblin on the basolateral side of Caco-2 cells after being placed on the apical side, and found that cytochalasin D, a tight junction opener, enhanced Cblin transport. Orally administered Cblin was found in rat plasma, indicating that intact Cblin was absorbed in vitro and in vivo. Furthermore, transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice. These findings indicated that CbR could serve as an alternative treatment for muscle atrophy., (© 2021. The Author(s).)

Distraction osteogenesis is a widely used surgical technique to treat bone deformity and shortening. Several biological treatments have been studied to enhance bone formation during distraction osteogenesis in animals. However, role of osteoactivin in the osseous tissues during distraction osteogenesis remains poorly understood. In this animal experimental study, we investigated the spatiotemporal expression of osteoactivin by immunohistochemistry and real-time PCR using a mouse model for tibial lengthening. Furthermore, to address the role of osteoactivin in bone lengthening, we subjected the osteoactivin-transgenic mice to distraction osteogenesis model. During the lag phase, the fibroblast-like cells (possible progenitors of the osteoblasts or chondrocytes), which mainly express osteoactivin, were infiltrated into the osteotomy site. Osteoactivin was ubiquitously expressed in the lengthened segment during the distraction and consolidation phases. Consistent with the immunohistochemical analysis, the levels of the osteoactivin transcripts in the tibias were significantly increased throughout the distraction osteogenesis process. The bone mineral content in the osteoactivin-transgenic mice calculated using peripheral quantitative computed tomography was also significantly increased at the remodeling zone. The histomorphometric analysis revealed that newly formed callus resorption in the remodeling zone was significantly reduced but bone formation was not altered in the osteoactivin-transgenic mice. We conclude that osteoactivin functions as an inhibitor of callus resorption during the consolidation phase of distraction osteogenesis., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)