Bone mineral density (BMD) reduction is heavily involved in osteoporosis. Bone marrow mesenchymal stem cells (BMSCs) are promising candidates in the implantation treatment of bone loss-related diseases. Traditional Chinese herbs and their active components are effective in osteoporosis therapy. The effects of linoleic acid on osteogenesis and osteoporosis have been investigated in this study, revealing multifaceted findings through several analyses and experiments. A total of 41 overlapping disease-drug target genes were obtained between differentially expressed genes in osteoporosis and linoleic acid potential targets. Linoleic acid was shown to enhance BMSC osteogenic differentiation and mineralization in in vitro assays. Additionally, linoleic acid significantly countered bone loss and improved bone microstructure in a mouse model of osteoporosis induced by ovarian varixectomy (OVX) operation. Molecular docking was used to predict the interaction between linoleic acid and the top ten Hub genes. The predicted binding energy of Retinoid X Receptor Alpha (RXRA) is the lowest. Moreover, linoleic acid stimulation increased the expression of RXRA in BMSCs. Functional enrichment and pathway analysis of the overlapping potential targets highlighted their involvement in crucial biological processes and signaling pathways, including the PI3K-AKT signaling. Linoleic acid promoted the phosphorylation of PI3K and AKT. Lastly, the siRNA for RXRA knockdown and PI3K/AKT inhibitor LY294002 exerted opposite effects on BMSCs to linoleic acid, and significantly attenuated the effects of linoleic acid on BMSC osteogenic differentiation and the PI3K/AKT signaling activation, suggesting that the functions of linoleic acid might be mediated by the PI3K/AKT signaling. Moreover, linoleic acid also inhibited osteoclastogenetic differentiation. Conclusively, linoleic acid, the main active compound of Rehmanniae Radix Praeparata (RR), could promote BMSC osteogenic differentiation by enhancing the PI3K/AKT signaling activation.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse lung inflammation and edema, with diffuse alveolar damage as the hallmark pathology. Paxillin plays a crucial role in the signaling pathways that regulate inflammatory responses. However, its involvement in modulating nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and its impact on lung epithelial integrity remain largely unexplored. Hematoxylin and eosin staining, immunohistochemistry, and Western blot (WB) analysis were performed. In the present study, lipopolysaccharide (LPS) stimulation significantly upregulated paxillin expression and phosphorylation concomitant with NLRP3 inflammasome activation. Co-immunoprecipitation was performed to assess the interaction between paxillin and NLRP3. To further explore the role of paxillin, a lentiviral knockdown approach was used to downregulate its expression. Paxillin knockdown attenuated the NLRP3 inflammasome-mediated inflammatory response in LPS-induced ALI/ARDS, leading to enhanced epithelial cell migration and improved wound healing capacity. In conclusion, paxillin plays a key role in regulating inflammation mediated by NLRP3 inflammasome. Overall, suppression of Paxillin expression provides protection by alleviating LPS-induced inflammation and promoting epithelial repair, thus highlighting its potential as a therapeutic target for ALI/ARDS.

Syndecans are a family of four-member transmembrane heparan sulfate proteoglycans that bind to various extracellular biomolecules, such as Wnt ligands, via their heparan sulfate chains, thereby controlling a variety of cellular processes. When dysregulated, syndecans can affect tumorigenesis and cancer progression by modulating key signaling pathways involved in the regulation of biological functions. Aberrant activation of Wnt/β-catenin signaling is a hallmark of many human tumors, including breast cancer. Studying the interplay between syndecans and Wnt signaling in human cancers is beneficial for identifying new therapeutic strategies, understanding tumor behavior and improving patient outcomes. Syndecan-2 is predominantly expressed by mesenchymal cells, and its overexpression in tumors of epithelial origin appears to induce aggressive behavior. Here, by measuring β-catenin cytoplasmic stabilization and transcriptional activity, we show that syndecan-2 expression significantly enhances the sensitivity of HEK293T cells and BT-20 triple-negative breast cancer cells to Wnt3a-induced activation of Wnt/β-catenin signaling. In addition, CRISPR/Cas9-mediated deletion of SDC2, the gene encoding syndecan-2, reduced β-catenin transcriptional activity in BT-20 cells in response to Wnt3a stimulation. This reduction was rescued by the re-expression of SDC2. Collectively, our results demonstrate that syndecan-2 is a positive regulator of canonical Wnt signaling. These results also suggest that syndecan-2 is a potential clinical target for inhibiting the progression of some human cancers.

Light-induced retinal damage is a significant contributor to age-related macular degeneration (AMD). Qihuang granule (QHG), a traditional Chinese herbal formulation, has been clinically employed in the treatment of retinal diseases, including AMD; however, the precise protective mechanisms remain unclear. This study investigated the protective effects and underlying mechanisms of QHG using a rat model of blue light-induced retinal injury and a human retinal pigment epithelial (ARPE-19) cell model. The results demonstrated that QHG significantly alleviated retinal morphological abnormalities, ultrastructural damage, and apoptosis induced by light exposure. Single-cell RNA sequencing further revealed that specific cell clusters were notably enriched in the PI3K-AKT-mTOR and autophagy-related signaling pathways after QHG treatment, characterized by increased MAP1LC3B (LC3B) expression and decreased SQSTM1 (P62) expression. Validation at the protein and gene levels in vivo confirmed that QHG activated the autophagy pathway by downregulating PI3K, AKT, mTOR, and P62 expression while upregulating LC3B expression. Collectively, this study demonstrates that QHG protects against retinal photodamage by modulating autophagy via the PI3K/AKT/mTOR signaling pathway, providing theoretical support for its clinical application in the treatment of AMD.

Type II diabetes is a prevalent chronic disease worldwide, yet no curative treatment currently exists. Compromised insulin release is one of the hallmarks of type II diabetes, to restore insulin release is one standard to screen candidates for therapy. Proton-activated chloride (PAC) channels are pH-sensitive chloride channels that open under acidic conditions, but their potential role in pancreatic β-cell physiology and diabetes has not been fully explored. In this study, we identified PAC on the membrane of pancreatic β-cells and found it to be closely associated with insulin secretory granules. Immunostaining and FRET imaging revealed that PAC is co-localized with Syntaxin 1 A and CaV1.2. Overexpression and knockdown of PAC increased and reduced L type calcium currents and steady capacitance jumps which reflect fast insulin secretion. Furthermore, manipulation of PAC expression significantly altered overall insulin release under high glucose conditions in vitro. Knockout of PAC channels in mice, however, affects body weight, fasting blood glucose levels, and serum insulin levels when constructing a type II diabetes model through high-fat diet feeding, compared to wild-type mice or Pac knockout mice fed a normal diet. Together, these findings reveal a previously unrecognized role for PAC in regulating both phases of insulin secretion and suggest that PAC channels could represent a novel therapeutic target for improving β-cell function and treating diabetes. Given the global burden of type II diabetes, understanding PAC channel function could open new avenues for targeted interventions to restore insulin secretion and improve disease outcomes.

DNA integrity and stability are vital for proper cellular activity. Nevertheless, to treat cancer patients, DNA is the main target for inducing tumoral cell death. Nowadays, cancer treatment is improving by the development of new technologies, protocols and strategies. Amongst them, the charged particle radiotherapies are becoming prevalent. However, tumor-neighboring healthy tissues are still exposed to ionizing radiation (IR) and subject to late side effects. Skeletal muscle is one of those tissues most likely to be affected. To decipher the DNA damage response (DDR) of skeletal muscle cells, myogenic cells, we irradiated them with microbeams of protons or α-particles and followed the accumulation of DDR proteins at localized irradiation sites. Thereby, we showed that myoblasts, proliferating myogenic cells, repair local IR-induced DNA damage through both non-homologous end-joining and homologous recombination with different recruitment dynamics depending on the characteristics of ionizing particles (type, energy deposition and time after irradiation), whereas myotubes, post-mitotic myogenic cells, display globally reduced DNA damage response.

Hepatocellular carcinoma (HCC) is a leading cause of cancer fatality worldwide. It is closely linked to the gut-liver axis, which plays a crucial role in nutrient metabolism, immune responses, and the biotransformation of bacterial metabolites. Traditional Chinese Medicine (TCM), as an adjuvant treatment, is important in the treatment course of HCC. This study aimed to explore the effects of Bielong Ruangan decoction (BLRG) on HCC. It is a traditional Chinese medicine formula used for liver fibrosis and cancer. The study focuses on its impact on gut microbiota and associated mechanisms. An orthotopic liver transplantation model was established in mice in the presence or absence of BLRG treatment, and the therapeutic effects of BLRG were evaluated. BLRG significantly inhibited tumor growth in an orthotopic liver transplantation mouse model, by reducing tumor size, liver weight, volume, Ki-67, and serum AFP levels. It also enhanced intestinal barrier functions by lowering serum LPS levels, increasing intestinal mucus thickness, and boosting ZO-1 and occludin mRNA levels. Moreover, BLRG modulated immune responses, decreasing inflammatory cytokines (IL-10 and IL-1β) while increasing anti-tumor cytokines (IFN-α, IFN-γ, and IL-2). A notable shift in gut microbiota composition was observed, accompanied by a decrease in Mucispirillum_sp. and Helicobacter_typhlonius post-treatment. Serum metabolomic profiling confirmed these findings and revealed a positive correlation between Mucispirillum and triglycerides (TG). Fecal Microbiota Transplantation (FMT) experiments further highlighted the gut microbiota's role in mediating BLRG's anti-tumor effects, demonstrating decreased tumor metrics and improved serum AFP levels, intestinal permeability, and immune responses in recipient mice. These results underscore BLRG's potential as an adjunctive therapeutic agent in liver cancer, demonstrating its ability to modulate tumor growth, gut microbiota, and immune responses, thereby potentially reshaping the HCC therapeutic landscape.

Coelonin is a dihydrophenanthrene compound derived from the traditional Chinese medicine Bletilla striata (Thunb.) Reichb.f., which exhibits significant anti-inflammatory activity and effectively inhibits lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. Although previous studies have demonstrated the protective effect of Bletilla striata against LPS-induced acute lung injury (ALI), the potential protective role and underlying molecular mechanisms of its major active component, Coelonin, in ALI remain unclear. In this study, an LPS-induced mouse ALI model was established to systematically evaluate the protective effects of Coelonin on ALI. Furthermore, transcriptomic analysis was utilized to investigate the anti-inflammatory mechanisms mediated by Coelonin through the regulation of non-coding RNA (ncRNA)-associated inflammatory pathways. The results indicated that Coelonin significantly ameliorated LPS-induced pathological damage in lung tissues and markedly reduced the levels of inflammatory markers in bronchoalveolar lavage fluid (BALF). In vitro experiments using the murine alveolar macrophages (MH-S) cell line further confirmed the anti-inflammatory activity of Coelonin. Transcriptome analysis revealed that Coelonin markedly upregulates the expression of the ncRNA Gm27505, which was previously found to be downregulated in a mouse model of Alzheimer's disease. To date, there have been no reports on the biological functions of Gm27505. Bioinformatics analysis and real-time quantitative fluorescence PCR (qPCR) confirmed that this ncRNA is primarily localized within the nucleus. Overexpression of Gm27505 in MH-S cells significantly downregulated the expression of inflammation-related genes such as Il6, Tnfα, Il27, and Ccl3 induced by LPS stimulation. Moreover, overexpression of Gm27505 promoted macrophage polarization toward the M2 phenotype while suppressing M1 polarization. These findings suggest that the ncRNA Gm27505 plays an important biological role and is critically involved in the regulation of inflammatory responses. Coelonin may alleviate LPS-induced ALI in mice by up-regulating Gm27505 expression and modulating macrophage polarization. Therefore, Gm27505 may represent a potential target for the prevention and treatment of ALI, providing new research directions for future therapeutic strategies against related diseases.

Autophagy is a promising therapeutic target for intervertebral disc degeneration (IDD). Previous study has shown down-regulation of activator protein 2α (AP-2α) promoted proliferation and inhibited senescence and apoptosis of rat nucleus pulposus (NP) cells in IDD. This study aimed to investigate the involvement of autophagy in IDD and the regulatory mechanism of AP-2α on autophagy. Rat NP cells were exposed to varying concentrations of HO. A rat IDD model was constructed and injected with AP-2α low expression adeno-associated virus. To study the role of AP-2α and autophagy in IDD, we constructed an IDD cell model using HO and treated NP cells with AP-2α low expression adeno-associated virus, autophagy activator rapamycin (RA) and autophagy inhibitor 3MA. In vitro, AP-2α (TFAP2A), LC3 (MAP1LC3A/B), Beclin-1 (BECN1), and p62 (Sequestosome 1, SQSTM1) levels were up-regulated after H₂O₂ treatment. In vivo, IDD increased the apoptosis degree of NP cells, but apoptosis was reduced after knockdown of AP-2α. Additionally, IDD increased AP-2α, LC3 II/I, Beclin-1, and p62 levels, but knockdown of AP-2α unblocked the autophagy flow. In vitro, H₂O₂ treatment increased AP-2α, LC3 II/I, Beclin-1, and p62 levels and NP cell apoptosis. Treatment with RA and its combined knockdown of AP-2α alleviated the dysfunction of autophagy flow and reduced the degree of apoptosis. Treatment with 3MA aggravated the dysfunction of autophagy flow and apoptosis, which can be alleviated by knockdown of AP-2α. Together, AP-2α regulated autophagy to participate in the development of IDD in vivo and rat NP cell model of IDD in vitro.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Fibroblast-like synovial cells (FLSs) are the main effector cells in the synovial microenvironment that cause chronic swelling and joint injury, and their enhanced glycolytic metabolism can lead to persistent joint injury. As a key regulatory enzyme in glycolysis, pyruvate kinase M2 (PKM2) plays a crucial role in the pathogenesis of RA. However, the exact mechanism by which PKM2 induces the inflammatory response of RA-FLSs through enhanced glucose metabolism and its impact on the pathogenic behaviour of cells remain unclear. This study detected the expression of PKM2 in synovial tissues and RA-FLSs of patients with RA and explored the effect of PKM2 on collagen-induced arthritis (CIA) rats. The results showed that PKM2 was upregulated in the synovial tissue of RA and RA-FLSs. PKM2 could promote glucose uptake, ATP and lactic acid production, and extracellular acidification rate in RA-FLSs, thereby promoting the release of pro-inflammatory cytokines such as TNF-α, interleukin-1 β (IL-1β), and IL-6. However, inhibiting PKM2 can reverse these changes. In in vivo experiments, inhibition of PKM2 could significantly improve the clinical arthritis symptoms of CIA rats (reduce plantar swelling and arthritis score), down-regulate the expression of pro-inflammatory cytokines, and inhibit bone erosion in CIA rats, reducing inflammatory cell infiltration, synovial hyperplasia and joint destruction. Furthermore, inhibiting PKM2 can suppress the phosphorylated expression of Akt and mTOR proteins, thereby inhibiting glycolytic reprogramming. Our research results indicate that PKM2 mediates glycolytic reprogramming to induce the release of RA-FLSs inflammatory cytokines by activating the Akt/mTOR signaling pathway, thereby promoting the progression of RA. Therefore, PKM2 may be a candidate target for the treatment of RA. Targeting PKM2 to regulate glycolytic reprogramming can provide a new idea for the treatment of RA.

Obesity is a major global health challenge closely associated with various metabolic diseases. A deeper understanding of the mechanisms underlying obesity, particularly the complex relationships between lipid metabolism, inflammation, and endoplasmic reticulum stress (ERS), is crucial for improving treatment strategies. This study proposes the hypothesis that "melatonin (MT) alleviates ERS-mediated inflammation in adipose tissue" and explores its mechanism of action. The results showed that MT effectively reduce ERS and its induced inflammatory response in adipose tissue and adipocytes of mice. Mechanistically, MT regulates the expression of the key ERS gene activating transcription factor 6(ATF6) by reducing the methylation level of the circadian clock gene period1 (PER1). Additionally, the study found that PER1 specifically binds to the promoter region of Atf6, thereby negatively regulating its expression and alleviating ERS. We also reveal that MT can effectively mitigate inflammation pathways mediated by ERS, including macrophage polarization and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation. This research not only uncovers the significant role of MT in regulating obesity-related inflammation but also provides new insights for future intervention strategies targeting obesity and its complications. A deeper understanding of the role and mechanism of MT in regulating ERS can lay the foundation for the development of new drugs for the treatment of obesity and metabolic diseases and provide enormous potential for clinical applications.

Mn is an important trace nutrient element in the body. Macrophages act a significant role on resisting Staphylococcus aureus (S. aureus). Nowadays, it remains unclear whether Mn can regulate the phagocytosis of macrophages against S. aureus through autophagy. Here, after the RAW264.7 cells transfected with the p3 × Flag-CMV10-ube2c plasmids were treated with Mn, subsequently infected with S. aureus, then these cells manifested that the expression levels of LC3-II and p62 proteins were significantly increased, and autophagosome formation was enhanced, and the expression level of RhoB phagocytosis-related protein also was significantly increased, the phosphorylation levels of mTOR, p38 and JNK were obviously decreased, while phosphorylation level of ERK was enhanced, the production levels of IL-6 and IL-2, IFN-β, IFN-γ, CAT and NO were significantly elevated, especially the phagocytosis against S. aureus was become obviously stronger. The data indicated that Mn could promote the early autophagy activation and inhibit the degradation of autophagolysosomes in the late stage of autophagy of RAW264.7 cells infected with S. aureus through Ube2C, thereby enhancing the phagocytosis of macrophages against S. aureus. These data provide an important basis for a deeper understanding of the molecular mechanism by which Mn enhances the phagocytosis of macrophages.

β-Tricalcium phosphate (β-TCP), frequently employed for bone tissue regeneration, can induce inflammation during the initial phases of implantation within the organism. However, mechanisms by which β-TCP nanoparticles (NPs) cause this inflammatory response is rarely reported. This project aims to investigate the causes of the macrophage inflammatory response induced by β-TCP NPs. Here, macrophage-like RAW264.7 cells were co-cultured with conditioned medium containing β-TCP NPs to identify the pathways through which β-TCP NPs influence inflammation and polarization of macrophages. This effect is achieved by modulating mitochondrial oxidative stress in the immune microenvironment. The results demonstrated that β-TCP NPs caused mitochondrial swelling, increased intracellular calcium ions, reduced mitochondrial membrane potential, as well as decreased the level of adenosine triphosphate (ATP) and translocase of outer mitochondrial membrane 20 (TOMM20). These NPs further lead to mitochondrial oxidative damage. These alterations promoted the polarization of macrophage to M1-type. Exogenous mitochondrial-targeted antioxidants could block this M1-type macrophage polarization. The findings of this work suggest that β-TCP NPs induce macrophage inflammation and contribute to M1 macrophage polarization, primarily through the activation of mitochondrial oxidative stress. These insights could guide the development of improved β-TCP formulations to mitigate inflammatory responses in bone regeneration applications.

Silicosis is a fatal occupational lung disease characterized by persistent inflammation and irreversible fibrosis. However, the pathogenesis of silicosis is currently unclear. In this study, a mouse model of silicosis was established by intranasal instillation of silica, and transcriptomic alterations in lung tissues were assessed by mRNA-sequencing. Cholesterol 25-hydroxylase (Ch25h) was upregulated in silicotic lung tissues and alveolar macrophages. Lentivirus-mediated Ch25h knockdown was then employed to assess its functional role in vivo. It was found that Ch25h knockdown alleviated associated pathological changes, including pulmonary injury and fibrosis. Additionally, Ch25h significantly modulated NLRP3 inflammasome activity in vivo and in vitro. Knockdown of Ch25h inhibited the secretion of inflammatory factor (IL-1α, IL-1β, and IL-18), decreased the protein level of cleaved caspase-1 and GSDMD-N in macrophages, and reduced potassium ion efflux and lactate dehydrogenase (LDH) release. Notably, ASC (apoptosis-related spotted protein) oligomerization was suppressed by Ch25h downregulation, suggesting that Ch25h was required for the inflammasome assembly. Our findings suggest that Ch25h may contribute to silicosis development by regulating NLRP3 inflammasome activation and pyroptosis, warranting further investigation as a possible therapeutic target.

Radiation induced lung injury (RILI) is a common complication in patients undergoing thoracic radiotherapy. At present, there are no effective early diagnostic biomarkers, and clinical treatment methods are very limited, which poses a huge challenge to the management of cancer patients. Oxidative stress has been recognized as a key mediator of aging and disease. Therefore, this study integrated multiple omics data in mice and advanced bioinformatics and machine learning methods to systematically analyze the molecular features associated with oxidative stress, and screened for clinically relevant biomarkers and molecular mechanisms of RILI. This study aims to provide a timely and practical theoretical basis for the early diagnosis and targeted intervention of RILI.

Muscle atrophy is observed in several pathophysiological situations, including physical inactivity, leading to negative health consequences, without any effective treatment currently available. Conversely, brown bears resist muscle atrophy during hibernation, despite prolonged physical inactivity and fasting. We previously reported that hibernating brown bear serum increases protein content in human myotubes and inhibits proteolysis. To go further, we deciphered here the transcriptional effects of brown bear serum in human myotubes using large-scale transcriptomics. After 48hours, the winter-hibernating bear serum (WBS) induced a specific transcriptomic program, affecting mostly biological pathways related to muscle growth and BMP signalling, compared to the summer-active bear (SBS) serum. WBS predominantly reduced, at mRNA and protein levels, activators and inhibitors of BMP signalling, which is associated with muscle mass maintenance. Moreover, BMP activity was more responsive to a stimulation by BMP7 at supra-physiological concentrations in human myotubes cultured in WBS versus SBS conditions. Meanwhile, WBS also up-regulated expression of genes encoding repressors of the pro-atrophic TGF-β pathway, decreased phosphorylated SMAD3 nuclear protein levels, and down-regulated TGF-β target genes. Furthermore, WBS treatment resulted in reduced TGF-β signalling responsiveness in human myotubes stimulated with TGF-β3 at physiological concentrations. Overall, even though WBS induced larger transcriptomic changes in the BMP compared to TGF-β pathway, the functional consequences were more pronounced for the TGF-β pathway with a marked inhibition. This study suggests that bioactive compounds in WBS may protect human muscle cells during catabolic situations, by regulating the TGF-β/BMP balance. These findings open new perspectives for therapies targeting muscle atrophy.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by impaired skin barrier function and immune dysregulation. Autophagy, a lysosome-dependent degradation pathway essential for removing unnecessary components, plays a crucial role in maintaining cellular homeostasis. Defective autophagy has been implicated in AD pathogenesis, and enhancing autophagic activity represents a viable therapeutic strategy. This study investigated the potential of the natural saponin escin to ameliorate AD through autophagy activation. We demonstrated that escin induced autophagy in HaCaT keratinocytes and mitigated tight junction (TJ) barrier disruption in an AD-like cell model stimulated with IL-4 and IL-13. Notably, silencing ATG7, an essential autophagy-related protein, abrogated the barrier-restorative effects of escin. Furthermore, in a 2,4-dinitrochlorobenzene (DNCB)-induced murine model of AD, escin treatment ameliorated AD-like skin lesions, reduced mast cell infiltration, and decreased cutaneous levels of the pro-inflammatory cytokines IL-4, IL-13, and IFN-γ. Escin administration also restored the epidermal expression of key TJ proteins, Claudin-1 and ZO-1. Mechanistically, escin promoted the nuclear translocation of transcription factor EB (TFEB) and upregulated the expression of genes involved in autophagy and lysosome biogenesis. These protective effects were associated with the activation of the AMPK-mTORC1-TFEB signaling pathway. Collectively, our findings indicate that escin enhances autophagy and restores skin barrier function, highlighting its potential as a novel therapeutic agent for AD treatment.

The biased agonism of glucagon-like peptide-1 receptor (GLP-1R) plays a key role in the efficacy and side effects of drugs used to treat type II diabetes mellitus and obesity. Despite its therapeutic potential, the mechanisms underlying GLP-1R biased agonism remain poorly understood. In this study, we investigate the role of the extracellular domain (ECD) in GLP-1R signaling bias through saturation mutagenesis at seven key sites. We examined 126 mutations and identified several that selectively abolished β-arrestin recruitment while retaining cAMP production. Additionally, we employed a large language model (LLM) to interpret the functional impacts of these mutations, uncovering correlations between sequence features and signaling outcome. These findings provide new insight into the "two-domain" model of class B1 G protein-coupled receptors (GPCRs), highlighting the ECD's role in biased agonism and offering novel information for designing more effective and selective GLP-1R agonists.

Ferroptosis occurs in osteoblasts in a diabetic environment, which impairs osteoblast number and function, promotes osteoblast death, destroys bone homeostasis, and eventually contributes to type 2 diabetic osteoporosis (T2DOP). Chromobox protein homolog 7 (CBX7) deficiency plays a positive role in bone formation and skeletal development. Besides, CBX7 interference has been reported to protect against disease development by inhibiting ferroptosis. This study focuses on determining whether CBX7 is involved in the progression of T2DOP by regulating osteoblast ferroptosis and explore the underlying mechanism.

This study aimed to elucidate the regulatory role of the muscle-specific gene ATP1B4 in skeletal muscle metabolism and mitophagy in diabetic sarcopenia (DS) rats.