Bazi Bushen alleviates skin senescence by orchestrating skin homeostasis in SAMP6 mice.

Bazi Bushen, a Chinese-patented drug with the function of relieving fatigue and delaying ageing, has been proven effective for extenuating skin senescence. To investigate the potential mechanism, senescence-accelerated mouse prone 6 (SAMP6) was intragastrically administered with Bazi Bushen for 9 weeks to induce skin homeostasis. Skin homeostasis is important in mitigating skin senescence, and it is related to many factors such as oxidative stress, SASP, apoptosis, autophagy and stem cell. In our study, skin damage in SAMP6 mice was observed using HE, Masson and SA-ß-gal staining. The content of hydroxyproline and the activities of SOD, MDA, GSH-PX and T-AOC in the skin were measured using commercial assay kits. The level of SASP factors (IL-6, IL-1ß, TNF-α, MMP2 and MMP9) in skin were measured using ELISA kits. The protein expressions of p16, p21, p53, Bax, Bcl-2, Cleaved caspase-3, LC3, p62, Beclin1, OCT4, SOX2 and NANOG were measured by western blotting. The expression of ITGA6 and COL17A1 was measured by immunofluorescence staining and western blotting. Our findings demonstrated that Bazi Bushen alleviated skin senescence by orchestrating skin homeostasis, reducing the level of oxidative stress and the expression of SASP, regulating the balance of apoptosis and autophagy and enhancing the protein expressions of ITGA6 and COL17A1 to improve skin structure in SAMP6 mice. This study indicated that Bazi Bushen could serve as a potential therapy for alleviating skin senescence.

Bazi Bushen maintains intestinal homeostasis through inhibiting TLR4/NFκB signaling pathway and regulating gut microbiota in SAMP6 mice.

BACKGROUND: Bazi Bushen is a Chinese patented medicine with multiple health benefits and geroprotective effects, yet, no research has explored its effects on intestinal homeostasis. In this study, we aimed to investigate the effect of Bazi Bushen on intestinal inflammation and the potential mechanism of gut microbiota dysbiosis and intestinal homeostasis in senescence-accelerated mouse prone 6 (SAMP6). The hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to assess the function of the intestinal mucosal barrier. The enzyme-linked immunosorbent assay (ELISA) and Western blotting were used to determine the level of intestinal inflammation. The aging-related ß-galactosidase (SA-ß-gal) staining and Western blotting were used to measure the extent of intestinal aging. The 16S ribosomal RNA (16S rRNA) was performed to analyze the change in gut microbiota composition and distribution. RESULTS: Bazi Bushen exerted remarkable protective effects in SAMP6, showing a regulated mucosal barrier and increased barrier integrity. It also suppressed intestinal inflammation through down-regulating pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) and inhibiting TLR4/NFκB signaling pathway (MYD88, p-p65, and TLR4). Bazi Bushen improved intestinal aging by reducing the area of SA-ß-gal-positive cells and the expression of senescence markers p16, p21, and p53. In addition, Bazi Bushen effectively rebuilt the gut microbiota ecosystem by decreasing the abundance of Bacteroides and Klebsiella, whiles increasing the ratio of Lactobacillus/Bacteroides and the abundance of Akkermansia. CONCLUSION: Our study shows that Bazi Bushen could serve as a potential therapy for maintaining intestinal homeostasis. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The ERα-NRF2 signalling axis promotes bicalutamide resistance in prostate cancer.

BACKGROUND: Bicalutamide is a nonsteroidal antiandrogen widely used as a first-line clinical treatment for advanced prostate cancer (PCa). Although patients initially show effective responses to bicalutamide treatment, resistance to bicalutamide frequently occurs and leads to the development of castration-resistant PCa (CRPC). This research investigated the roles of the oestrogen receptor α (ERα)-nuclear factor E2-related factor 2 (NRF2) signalling pathway in bicalutamide resistance in PCa cells. METHODS: We performed bioinformatic analysis and immunohistochemical staining on normal and cancerous prostate tissue to evaluate ERα and NRF2 expression and their correlation. Gene expression and localization in PCa cell lines were further investigated using real-time reverse transcription PCR/Western blotting and immunofluorescence staining. We treated PCa cells with the ER inhibitor tamoxifen and performed luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays to understand ERα-dependent NRF2 expression. Overexpression and knockdown of ERα and NRF2 were used to explore the potential role of the ERα-NRF2 signalling axis in bicalutamide resistance in PCa cells. RESULTS: We found that the expression of ERα and NRF2 was positively correlated and was higher in human CRPC tissues than in primary PCa tissues. Treatment with oestrogen or bicalutamide increased the expression of ERα and NRF2 as well as NRF2 target genes in PCa cell lines. These effects were blocked by pretreatment with tamoxifen. ChIP assays demonstrated that ERα directly binds to the oestrogen response element (ERE) in the NRF2 promoter. This binding led to increased transcriptional activity of NRF2 in a luciferase reporter assay. Activation of the ERα-NRF2 signalling axis increased the expression of bicalutamide resistance-related genes. Inhibition of this signalling axis by knockdown of ERα or NRF2 downregulated the expression of bicalutamide resistance-related genes and inhibited the proliferation and migration of PCa cells. CONCLUSIONS: We demonstrated the transcriptional interaction between ERα and NRF2 in CRPC tissues and cell lines by showing the direct binding of ERα to the ERE in the NRF2 promoter under oestrogen treatment. Activation of the ERα-NRF2 signalling axis contributes to bicalutamide resistance in PCa cells, suggesting that the ERα-NRF2 signalling axis is a potential therapeutic target for CRPC. Video Abstract.

Neuroprotection of Triptolide against Amyloid-Beta1-42-induced toxicity via the Akt/mTOR/p70S6K-mediated Autophagy Pathway.

Triptolide is a natural active compound that has significant neuroprotective properties and shows promising effects in the treatment of Alzheimer's disease (AD). Recent studies have shown that autophagy occurs in AD. In this study, we determined whether autophagy regulated by triptolide ameliorates neuronal death caused by amyloid-Beta1-42 (Aß1-42). We examined the effects of triptolide on cell viability, autophagy, apoptosis, and the protein kinase B/mammalian target of the rapamysin/70 kDa ribosomal protein S6 kinase (Akt/mTOR/p70S6K) signaling pathway in PC12 cells. The results indicated that triptolide treatment exhibited a cytoprotective effect against cell injury induced by Aß1-42. Triptolide also reduced apoptosis and enhanced cell survival by decreasing autophagosome accumulation and inducing autophagic degradation. Furthermore, our results also showed that activating the Akt/mTOR/p70S6K mechanism was one reason for the protection of triptolide. Triptolide treatment protected against Aß1-42-induced cytotoxicity by decreasing autophagosome accumulation, and inducing autophagic degradation in PC12 cells. These findings also suggest that the reduction of autophagosome accumulation observed in triptolide-treated cells was Akt/mTOR/p70S6K pathway dependent. Overall, triptolide exhibits a neuron protective effect and this study provides new insight into AD prevention and treatment.

GPR30 knockdown weakens the capacity of CAF in promoting prostate cancer cell invasion via reducing macrophage infiltration and M2 polarization.

Cancer-associated fibroblasts (CAFs) can promote the development and metastasis of prostate cancer partly by mediating tumor-associated inflammation. An increasing amount of studies have focused on the functional interactions between CAFs and immune cells in the tumor microenvironment (TME). We previously reported that G protein-coupled receptor 30 (GPR30) was highly expressed in prostate CAFs and plays a crucial role in prostate stromal cell activation. However, the effect and underlying mechanism of GPR30 expression in prostate CAFs affecting the interaction between CAFs and tumor-associated macrophages (TAMs) need further elucidation. Here, we found that, compared with CAF-shControl, CAF-shGPR30 inhibited macrophage migration through transwell migration assays, which should be attributed to the decreased expression of C-X-C motif chemokine ligand 12 (CXCL12). In addition, macrophages treated with a culture medium of CAF-shGPR30 exhibited attenuated M2 polarization with downregulated M2-like markers expression. Moreover, macrophages stimulated with a culture medium of CAF-shGPR30 were less efficient in promoting activation of fibroblast cells and invasion of PCa cells. Finally, cocultured CAF-shGPR30 and macrophages suppressed PCa cell invasion compared to cocultured CAF-shControl and macrophages by decreasing interleukin-6 (IL-6) secretion, and this effect could be abrogated with rescue expression of IL-6. Our results pinpoint the function of GPR30 in prostate CAFs on regulating the CAF-TAM interaction in the TME and provide new insights into PCa therapies via regulating TME.

Glycan Markers of Human Stem Cells Assigned with Beam Search Arrays.

Glycan antigens recognized by monoclonal antibodies have served as stem cell markers. To understand regulation of their biosynthesis and their roles in stem cell behavior precise assignments are required. We have applied state-of-the-art glycan array technologies to compare the glycans bound by five antibodies that recognize carbohydrates on human stem cells. These are: FC10.2, TRA-1-60, TRA-1-81, anti-i and R-10G. Microarray analyses with a panel of sequence-defined glycans corroborate that FC10.2, TRA-1-60, TRA-1-81 recognize the type 1-(Galß-3GlcNAc)-terminating backbone sequence, Galß-3GlcNAcß-3Galß-4GlcNAcß-3Galß-4GlcNAc, and anti-i, the type 2-(Galß-4GlcNAc) analog, Galß-4GlcNAcß-3Galß-4GlcNAcß-3Galß-4GlcNAc, and we determine substituents they can accommodate. They differ from R-10G, which requires sulfate. By Beam Search approach, starting with an antigen-positive keratan sulfate polysaccharide, followed by targeted iterative microarray analyses of glycan populations released with keratanases and mass spectrometric monitoring, R-10G is assigned as a mono-sulfated type 2 chain with 6-sulfation at the penultimate N-acetylglucosamine, Galß-4GlcNAc(6S)ß-3Galß-4GlcNAcß-3Galß-4GlcNAc. Microarray analyses using newly synthesized glycans corroborate the assignment of this unique determinant raising questions regarding involvement as a ligand in the stem cell niche.

Epicatechin gallate prevents the de novo synthesis of fatty acid and the migration of prostate cancer cells.

Lipid metabolism disorder caused by the upregulation of lipogenic genes is a typical feature of prostate cancer. The synthesis of fatty acids is enhanced to accelerate the development of prostate cancer and is considered as a potential therapeutic target. Epicatechin gallate, an active compound of green tea, has been reported to modulate lipid metabolism. In this research, the potential role of epicatechin gallate in prostate cancer cells was evaluated. The results indicated that epicatechin gallate downregulates the expression of acetyl-CoA carboxylase, ATP citrate lyase, and fatty acid synthase in prostate cancer cells and prostate xenograft tissues, suggesting that epicatechin gallate can inhibit de novo fatty acid synthesis. Moreover, epicatechin gallate significantly restrains the migration rather than the viability of prostate cancer cells. PI3K/AKT/mTOR signaling pathway, which exhibits regulatory effect on lipogenesis, is also inhibited under epicatechin gallate treatment, while pretreatment with AKT activator SC79 or mTOR activator MHY1485 blocks the inhibitory effect of epicatechin gallate on the expression of lipogenic genes and the migration of prostate cancer cells. In conclusion, this study revealed that epicatechin gallate impairs the synthesis of fatty acids via inhibition PI3K/AKT/mTOR signaling pathway and then attenuates the migration of prostate cancer cells.

Estrogen receptor α-NOTCH1 axis enhances basal stem-like cells and epithelial-mesenchymal transition phenotypes in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of mortality and a leading cause of malignant tumors in males. Prostate cancer stem cells (PCSCs) are likely the responsible cell types for cancer initiation, clinical treatment failure, tumor relapse, and metastasis. Estrogen receptor alpha (ERα) is mainly expressed in the basal layer cells of the normal prostate gland and has key roles in coordinating stem cells to control prostate organ development. Here, we investigated the roles of the estrogen-ERα signaling pathway in regulating PCSCs. METHODS: Correlation of CD49f and ERα/NOTCH1 was analyzed in human clinical datasets and tissue samples. Flow cytometry was used to sort CD49fHi and CD49fLow cells. EZH2 recruitment by ERα and facilitation of ERα binding to the NOTCH1 promoter was validated by Co-IP and ChIP. Primary tumor growth, tumor metastasis and sensitivity to 17ß-estradiol (E2) inhibitor (tamoxifen) were evaluated in castrated mice. RESULTS: ERα expression was significantly higher in CD49fHi prostate cancer basal stem-like cells (PCBSLCs), which showed basal and EMT features with susceptibility to E2 treatment. ERα-induced estrogen effects were suggested to drive the NOTCH1 signaling pathway activity via binding to the NOTCH1 promoter. Moreover, EZH2 was recruited by ERα and acted as a cofactor to assist ERα-induced estrogen effects in regulating NOTCH1 in PCa. In vivo, E2 promoted tumor formation and metastasis, which were inhibited by tamoxifen. CONCLUSIONS: Our results implicated CD49f+/ERα + prostate cancer cells associated with basal stem-like and EMT features, named EMT-PCBSLCs, in heightened potential for promoting metastasis. NOTCH1 was regulated by E2 in CD49fHi EMT-PCBSLCs. These results contribute to insights into the metastatic mechanisms of EMT-PCBSLCs in PCa.

Comparison of the Interactions of Different Growth Factors and Glycosaminoglycans.

Most growth factors are naturally occurring proteins, which are signaling molecules implicated in cellular multiple functions such as proliferation, migration and differentiation under patho/physiological conditions by interacting with cell surface receptors and other ligands in the extracellular microenvironment. Many of the growth factors are heparin-binding proteins (HBPs) that have a high affinity for cell surface heparan sulfate proteoglycans (HSPG). In the present study, we report the binding kinetics and affinity of heparin interacting with different growth factors, including fibroblast growth factor (FGF) 2,7,10, hepatocyte growth factor (HGF) and transforming growth factor (TGF ß-1), using a heparin chip. Surface plasmon resonance studies revealed that all the tested growth factors bind to heparin with high affinity (with KD ranging from ~0.1 to 59 nM) and all the interactions are oligosaccharide size dependent except those involving TGF ß-1. These heparin-binding growth factors also interact with other glycosaminoglycans (GAGs), as well as various chemically modified heparins. Other GAGs, including heparan sulfate, chondroitin sulfates A, B, C, D, E and keratan sulfate, showed different inhibition activities for the growth factor-heparin interactions. FGF2, FGF7, FGF10 and HGF bind heparin but the 2-O-sulfo and 6-O-sulfo groups on heparin have less impact on these interactions than do the N-sulfo groups. All the three sulfo groups (N-, 2-O and 6-O) on heparin are important for TGFß-1-heparin interaction.

Glycosaminoglycans from bovine eye vitreous humour and interaction with collagen type II.

Glycosaminoglycans (GAGs) play an important role in stabilizing the gel state of eye vitreous humour. In this study, the composition of GAGs present in bovine eye vitreous was characterized through disaccharide analysis by liquid chromatography-mass spectrometry. The interaction of GAGs with collagen type II was assessed using surface plasmon resonance (SPR). The percentage of hyaluronic acid (HA), chondroitin sulfate (CS) and heparan sulfate (HS), of total GAG, were 96.2%, 3.5% and 0.3%, respectively. The disaccharide composition of CS consisted of 4S (49%), 0S (38%) 6S (12%), 2S6S (1.5%) and 2S4S (0.3%). The disaccharide composition of HS consisted of 0S (80%), NS2S (7%), NS (7%), 6S (4%), NS6S (2%), and TriS, 2S and 4S6S (each at 0.1%). The average molecular weights of CS and HS were 148 kDa and 204 kDa, respectively. SPR reveals that collagen type II binds to heparin (primarily composed of TriS) with a binding affinity (K D) of 755 nM and interacts with other GAGs, including CSB and CSE. Both bovine vitreous CS and HS interact with collagen type II, with vitreous HS showing a higher binding affinity.

Dietary Natural N-Acetyl-d-Glucosamine Prevents Bone Loss in Ovariectomized Rat Model of Postmenopausal Osteoporosis.

Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.

Estradiol promotes epithelial-to-mesenchymal transition in human benign prostatic epithelial cells.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is involved in pathogenesis of human benign prostatic hyperplasia (BPH). Estrogenic signaling pathways may stimulate the induction of EMT. However, the details of estradiol (E2) and estrogen receptors (ERs) effects on EMT, as well as E2-induced modulation of benign prostatic epithelial cell phenotype in vitro have not been completely clarified. METHODS: The effects of E2 on EMT markers and cytokeratins (CKs) expression were evaluated in benign epithelial cell lines BPH-1 and RWPE-1, which were cultured both in two-dimensional (2D) culture and three-dimensional (3D) culture model using hanging drop technique or 3D Matrigel model. ER antagonist, ICI182,780, was used to confirm the regulatory effects of E2 on EMT and phenotypic modulation. In 3D culture, immunohistochemical stainings were performed to detect the specific phenotype of cells that underwent EMT in acinar-like spheroids formed by RWPE-1. To illustrate the exact function of ERs in E2-induced EMT and phenotypic modulation, specific short interfering RNAs (siRNAs), and agonists were used to knockdown or activate individual ERs, respectively. RESULTS: E2-induced EMT was observed both in 2D and 3D culture, with related regulation of EMT markers expression at both mRNA and protein level. In addition, E2 down-regulated luminal cell type markers CK18 and CK8 and up-regulated basal cell type markers CK5 and CK14. E2 also increased intermediate type markers CK15 and CK17, while it attenuated CK19 in 3D culture. ICI182,780 blocked E2-induced EMT and cell phenotypic switching. In 3D Matrigel culture, Vimentin was co-expressed with ERα and CK17, as well as with SMemb, which is related to cell status switching and proliferation. Knockdown of ERα but not GPR30 inhibited EMT, while ERß knockdown facilitated EMT process. Knockdown of ERα blocked E2-induced EMT both in RWPE-1 and BPH-1. MRNA expression of EMT markers was stimulated by ERα-specific agonist PPT and inhibited by ERß-specific agonist DPN. CONCLUSIONS: Estrogenic effect mediated by ERα can promote EMT. E2 is also an inductive factor of cell phenotypic switching. Cell type modulation is associated with E2-induced EMT in benign prostatic epithelial cells. Taken together the results support a contribution of estrogens to the pathogenesis of BPH in elderly men.

Physalin A induces G2/M phase cell cycle arrest in human non-small cell lung cancer cells: involvement of the p38 MAPK/ROS pathway.

Physalin A (PA) is an active withanolide isolated from Physalis alkekengi var. franchetii, a traditional Chinese herbal medicine named Jindenglong, which has long been used for the treatment of sore throat, hepatitis, and tumors in China. In the present study, we firstly investigated the effects of PA on proliferation and cell cycle distribution of the human non-small cell lung cancer (NSCLC) A549 cell line, and the potential mechanisms involved. Here, PA inhibited cell growth in dose- and time-dependent manners. Treatment of A549 cells with 28.4 µM PA for 24 h resulted in approximately 50 % cell death. PA increased the amount of intracellular ROS and the proportion of cells in G2/M. G2/M arrest was attenuated by the addition of ROS scavenger NAC. ERK and P38 were triggered by PA through phosphorylation in a time-dependent manner. The phosphorylation of ERK and P38 were not attenuated by the addition of NAC, but the use of the p38 inhibitor could reduce, at least in part, PA-induced ROS and the proportion of cells in G2/M. PA induces G2/M cell cycle arrest in A549 cells involving in the p38 MAPK/ROS pathway. This study suggests that PA might be a promising therapeutic agent against NSCLC.

Efficient Expression and Characterization of an Endo-Type Lyase HCLase_M28 and Its Gradual Scale-Up Fermentation for the Preparation of Chondroitin Sulfate Oligosaccharides.

Glycosaminoglycan (GAG) lyases have been critical in structural and functional studies of GAGs. HCLase_M28, a lyase identified from the genome of Microbacterium sp. M28 was heterologously expressed, enzymatically characterized, and prepared in large-scale fermentation for the production of chondroitin sulfate (CS) oligosaccharides. Results showed that the expression of HCLase_M28 in Escherichia coli BL21 (DE3)-pET24a-HCLase_M28opt1 and Bacillus subtilis W800-pSTOP1622-HCLase_M28opt2 were 108-fold and 25-fold that of wide strain. The optimal lytic reaction of HCLase_M28 happened in 20 mM Tris-HCl (pH 7.2) at 50 °C with a specific activity of 190.9 U/mg toward CS-A. The degrading activity was slightly simulated in presence of 1 mM Ca2+ and Mn2+ while severely inhibited by Hg+, Cu2+, Fe3+, and SDS. TLC and ESI-MS analysis proved HCLase_M28 was an endolytic lyase and degraded CS and hyaluronic acid into unsaturated disaccharides. Through a gradual scale-up of fermentation in 5 L, 100 L, and 1000 L, a highly efficient intracellular expression of HCLase_M28 with an activity of 3.88 × 105 U/L achieved within a 34 h of cultivation. Through ultrafiltration, CS oligosaccharides with DP of 2 to 8 as the main components could be controllably prepared. The successful large-scale fermentation made HCLase_M28 a promising enzyme for industrial production of CS oligosaccharides.

Role of epigenetics in the regulation of skin aging and geroprotective intervention: A new sight.

Multiple epigenetic factors play a regulatory role in maintaining the homeostasis of cutaneous components and are implicated in the aging process of the skin. They have been associated with the activation of the senescence program, which is the primary contributor to age-related decline in the skin. Senescent species drive a series of interconnected processes that impact the immediate surroundings, leading to structural changes, diminished functionality, and heightened vulnerability to infections. Geroprotective medicines that may restore the epigenetic balance represent valid therapeutic alliances against skin aging. Most of them are well-known Western medications such as metformin, nicotinamide adenine dinucleotide (NAD+), rapamycin, and histone deacetylase inhibitors, while others belong to Traditional Chinese Medicine (TCM) remedies for which the scientific literature provides limited information. With the help of the Geroprotectors.org database and a comprehensive analysis of the referenced literature, we have compiled data on compounds and formulae that have shown potential in preventing skin aging and have been identified as epigenetic modulators.

Glycyrrhiza polysaccharides may have an antitumor effect in γδT cells through gut microbiota and TLRs/NF-κB pathway in mice.

Tumor immunotherapy can be a suitable cancer treatment option in certain instances. Here we investigated the potential immunomodulatory effect of oral glycyrrhiza polysaccharides (GCP) on the antitumor function of γδT cells in intestinal epithelial cells in mice. We found that GCP can inhibit tumor growth and was involved in the regulation of systemic immunosuppression. GCP administration also promoted the differentiation of gut epithelia γδT cells into IFN-γ-producing subtype through regulation of local cytokines in gut mucosa. GCP administration increased local cytokine levels through gut microbiota and the gut mucosa Toll-like receptors / nuclear factor kappa-B pathway. Taken together, our results suggest that GCP might be a suitable candidate for tumor immunotherapy, although further clinical research, including clinical trials, are required to validate these results.

Insights into the epitranscriptomic role of N6-methyladenosine on aging skeletal muscle.

The modification of RNA through the N6-methyladenosine (m6A) has emerged as a growing area of research due to its regulatory role in gene expression and various biological processes regulating the expression of genes. m6A RNA methylation is a post-transcriptional modification that is dynamic and reversible and found in mRNA, tRNA, rRNA, and other non-coding RNA of most eukaryotic cells. It is executed by special proteins known as "writers," which initiate methylation; "erasers," which remove methylation; and "readers," which recognize it and regulate the expression of the gene. Modification by m6A regulates gene expression by affecting the splicing, translation, stability, and localization of mRNA. Aging causes molecular and cellular damage, which forms the basis of most age-related diseases. The decline in skeletal muscle mass and functionality because of aging leads to metabolic disorders and morbidities. The inability of aged muscles to regenerate and repair after injury poses a great challenge to the geriatric populace. This review seeks to explore the m6A epigenetic regulation in the myogenesis and regeneration processes in skeletal muscle as well as the progress made on the m6A epigenetic regulation of aging skeletal muscles.

Enzymatic preparation of chondroitin sulfate oligosaccharides and its alleviating effect on ovariectomy-induced osteoporosis in rats.

Postmenopausal osteoporosis is the most common type of osteoporosis. Chondroitin sulfate (CS) has been successfully employed as food supplement against osteoarthritis, while the therapeutic potential on postmenopausal osteoporosis is little explored. In this study, CS oligosaccharides (CSOs) were enzymatically prepared through the lysis of CS by a chondroitinase from Microbacterium sp. Strain. The alleviating effects of CS, CSOs and Caltrate D (a clinically used supplement) on ovariectomy (OVX) - induced rat's osteoporosis were comparatively investigated. Our data showed that the prepared CSOs was basically unsaturated CS disaccharide mixture of ∆Di4S (53.1%), ∆Di6S (27.7%) and ∆Di0S (17.7%). 12 weeks' intragastric administration of Caltrate D (250 mg/kg/d), CS or CSOs (500 mg/kg/d, 250 mg/kg/d, 125 mg/kg/d) could obviously regulate the disorder of serum indices, recover the mechanical strength and mineral content of bone, improve the cortical bones' density and the number and length of trabecular bones in OVX rats. Both CS and CSOs in 500 mg/kg/d and 250 mg/kg/d could restore more efficiently the serum indices, bone fracture deflection and femur Ca than Caltrate D. As compared with CS at the same dosage, CSOs exhibited a more significant alleviating effect. These findings suggested that there was great potential of CSOs as daily interventions for delaying the progression of postmenopausal osteoporosis.

Effects of molecular weights on the absorption, distribution and urinary excretion of intraperitoneally administrated carboxymethyl chitosan in rats.

Carboxymethyl chitosan (CM-chitosan) is one of water-soluble derivatives of chitosan. Numerous studies have been focused on its applications as pharmaceutical excipient, bioactive reagent and nontoxic drug carrier. Like other polysaccharides, CM-chitosan is inhomogenous in molecular weight. Originations and preparation procedures considerably influence its molecular weight and molecular weight distributions. Understanding the molecular weight related biological behaviour of this inhomogenous glycopolymer in vivo were crucial for the quality control and clinical applications of chitosan and chitosan based medical devices. In this study, we investigated the effects of molecular weights on the absorption, distribution, degradation and urinary excretion of the fluorescein isothiocyanate-labeled CM-chitosan in rats. The results indicated that molecular weight significantly influenced the uptake of CM-chitosan from the lumen of abdomen and blood vessels to peripheral tissues, the distribution of this chemical and urinary excretion after intraperitoneal administration. These findings provided an important reference for the clinical applications of this versatile derivative of chitosan as postsurgical and other biomedical materials and important clues for the exploitation of CM-chitosan based drug targeting and delivery systems.