Introduction: Diabetic Cardiomyopathy (DCM) is a diabetes-specific cardiac complication characterized by a complex network of pathogenic mechanisms and lacks effective drugs at present. Traditional Chinese Medicine (TCM) offers a holistic and multi-target therapeutic strategy; however, its clinical translation remains challenging. This review provides a comprehensive overview of the current evidence and challenges associated with TCM for DCM, aiming to promote its clinical application and translation. Methods: Preclinical and clinical studies published between 2004 and 2026 were retrieved from Google Scholar, PubMed, ScienceDirect, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data. The literature search was conducted using the following keywords: “diabetic cardiomyopathy”, “DCM”, “traditional Chinese medicine”, “Chinese herbal formulas”, and “active components of Chinese herbs”. Results: Preclinical evidence has demonstrated that both TCM formulas and monomers exert significant cardioprotective effects in DCM. These agents act on multiple key pathogenic pathways, particularly by attenuating oxidative stress, inhibiting fibrosis, alleviating endoplasmic reticulum stress, and modulating gut microbiota dysbiosis, thereby effectively preventing cellular injury and death. However, clinical trials and evidence remain limited. Discussion: The multi-target therapeutic profile of TCM closely matches the multifactorial pathogenesis of DCM, representing a potential paradigm shift from conventional single-target interventions. Furthermore, high-quality trials of TCM in other cardiovascular disorders have demonstrated the feasibility of rigorous randomized and blinded study designs, providing a solid methodological foundation for future translational and clinical research on TCM-based therapies for DCM. Conclusion: TCM provides an innovative therapeutic strategy for DCM by simultaneously intervening in cascaded pathogenic pathways that single-target drugs fail to address adequately. Despite solid preclinical efficacy support, sufficient clinical verification is absent. Conducting high-quality translational research and multicenter randomized controlled trials is critical to translate laboratory outcomes into clinical practice and integrate TCM into standardized DCM treatment regimens.

Perfluorooctanoic acid (PFOA), a widely distributed environmental pollutant, exerts toxic effects on multiple human organs and tissues. However, its impact on skeletal muscle function and the underlying molecular mechanisms remain poorly understood. In this study, we first observed that PFOA exposure caused muscle dysfunction in juvenile mice, characterized by reduced grip strength and impaired motor coordination; to explore the underlying mechanism, we further conducted in vitro experiments using C2C12 myoblasts. Long-term treatment with 100 mu acid (PFOA), a widely distributed environmental pollutant, exerts toxic effects on multiple human organs and tissues. However, its impact on myotubes. Transcriptome sequencing revealed a significant decrease in the expression of key myogenic regulatory factors (e.g., myosin heavy chain MYHC and myogenin) in PFOA-treated cells, findings that were confirmed by RT-qPCR and Western blot analyses. Mechanistically, PFOA treatment activated the Hippo signaling pathway, as evidenced by increased phosphorylation of the YAP protein. Treatment with taurine, an indirect activator of YAP, significantly restored the expression of myogenic genes and effectively promoted myotube formation. In summary, this study demonstrates that PFOA impairs muscle function by activating the Hippo signaling pathway and suppressing the transcription of key myogenic factors, providing new insights into PFOA-induced myotoxicity.

High enrichment of N-nitrosamines (NAs) and microcystins (MCs) in drinking water are major risk factors in high-risk areas of esophageal squamous cell carcinoma (ESCC) in China, however, their combined effects and underlying carcinogenic mechanisms remain unknown. The scRNA_seq sequencing and CTD database were used to identify the “chemical-epithelial cell” associated carcinogenic targets. An ESCC rat model was established to confirm the combined effect of NAs and MCs; RNA-Seq was performed to screen potential circRNAs in ESCC and matched adjacent normal tissues. Malignant transformation of esophageal epithelial cells (Het-1A-T) was induced by exposure to N-nitrosomethylbenzylamine (NMBzA) and Microcystin-LR (MC-LR). The biological function of hsa_circ_0063865 was investigated using gain- and loss-of-function experiments in vitro and in vivo. RNA pull-down, ChIRP, RIP, Co-IP and luciferase reporter assays were used to elucidate the underlying mechanisms of hsa_circ_0063865 in chemically related ESCC. The rat ESCC model and median-effect principle showed a synergistic effect of NAs and MC-LR in chemical carcinogenesis. Further, integration of single-cell and network toxicology revealed 292 “chemical-epithelial cell” associated carcinogenic targets, which were primarily involved in microRNA in cancer and cytoskeleton rearrangements. At the molecular level, the chemical carcinogenesis-related hsa_circ_0063865 was identified and found to be up-regulated in ESCC tissues. Functionally, hsa_circ_0063865 promoted malignant transformation of Het-1A cells induced by NMBzA and MC-LR by promoting cytoskeletal rearrangements and inhibiting ER stress of MYH9+ epithelial cell. Mechanistically, hsa_circ_0063865 acted as a modular scaffold to tether eEF1A2(126-177nt of hsa_circ_0063865) and NMIIA (601-658nt of hsa_circ_0063865), thereby promoting NMIIA translation by enhancing the interaction between eEF1A2 and NMIIA, which further promoted cytoskeletal reorganization; Additionally, hsa_circ_0063865 competitively upregulated RCN1 expression by sponging miR-450b-3p, resulting in ER stress inhibition and depolarization of mitochondrial membrane potential via activation of the PERK-eIF2α-ATF4-CHOP axis in MYH9+ epithelial cell. These findings identify a novel chemical carcinogenic target and elucidate the dual-regulatory mechanism of hsa_circ_0063865 in NAs and MC-LR-induced esophageal carcinogenesis.

[This corrects the article DOI: 10.1016/j.jgr.2020.08.005.].

ETHNOPHARMACOLOGICAL RELEVANCE:Panax japonicus (T. Nees) C.A. Mey. (PJ) is a traditional Chinese herbal medicine revered as the "King of Herbs" in Tujia and Hmong medical practices. Clinically, it is primarily used to treat weakness and fatigue, wound bleeding, arthritis, hyperlipidemia, and fatty liver. It is rich in saponins, and the total saponins from PJ (TSPJ), possess immunomodulatory, antioxidant, and lipid-lowering effects. These properties hold significant potential in managing liver-related metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). AIM OF STUDY:Evaluate the therapeutic effects of TSPJ on lipid metabolism disorders in a NASH model and explore the possible underlying mechanisms. MATERIALS AND METHODS:To model NASH, C57BL/6J mice were fed a high-fat diet (HFD) and RAW264.7 cells were stimulated with lipopolysaccharide (LPS) and palmitic acid (PA). The animal and cell models were also treated with TSPJ, and the changes in inflammation and lipid metabolism were measured. Additional models were created by transfecting lentiviral vectors to cause miR-463-5p knockdown in the C57BL/6J mouse and the RAW264.7 cells. RESULTS:In the HFD-induced mice, TSPJ reduced the body weight and liver weight, lowered the serum levels of TG, T-CHO, ALT, and AST, and reduced the hepatic lipid droplet formation and vacuolization. In the RAW264.7 cells, TSPJ upregulated the M2 markers and downregulated the M1 markers. TSPJ also significantly increased the expression of miR-463-5p in the exosomes derived from the RAW264.7 cells or the primary mouse hepatic macrophages, and miR-463-5p suppressed the expression of PHD2 in hepatocytes to improve lipid metabolism. However, when the exosome secretion inhibitor GW4869 was applied, TSPJ became less effective in alleviating the lipid deposition and inflammation in hepatocytes. CONCLUSIONS:TSPJ significantly upregulated the expression of miR-463-5p in the exosomes of hepatic macrophages to thus downregulate PHD2 expression in hepatocytes and improve hepatic lipid metabolism.

Chronic metabolic inflammation in adipose tissue plays an important role in the development of obesity-associated diseases. Our previous study indicated that total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one main component of SPJ, could exert the anti-oxidative and anti-inflammatory effects. The present study aimed to investigate the in vivo and Ex vivo anti-inflammatory activities of another main component of SPJ, namely Chikusetsu saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis, and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA expression levels of inflammation-related genes and secretion of the chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages (ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced expression of NLRP3 inflammasome component genes and decreased IL-1β and Caspase-1 production in mice. Moreover, CS treatment also inhibited the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs). Meanwhile, CS treatment inhibited an NLRP3-induced ASC pyroptosome formation and lipopolysaccharide (LPS)-induced pyroptosis. Furthermore, CS treatment suppressed HFD-induced NF-κB signaling in vivo and LPS-induced NF-κB activation as reflected by the fact that their phosphorylated forms and the ratios of pNF-κB/NF-κB, pIKK/IKK, and pIκB/IκB were all decreased in EAT from HFD-fed mice treated with CS as compared with those of HFD mice. Taking together, this study has revealed that CS effectively inhibits HFD-induced inflammation in adipose tissue of mice through inhibiting both NLRP3 inflammasome activation and NF-κB signaling. Thus, CS can serve as a potential therapeutic drug in the prevention and treatment of inflammation-associated diseases.

Background: MiR-136-5p plays a vital function in regulating developmental processes as well as in the pathophysiology of diseases, with a notable record in tumor suppression. Methods: This article summarizes the latest findings on the physiological and pathophysiological processes of miR-136-5p in diseases. We searched for relevant studies and selected research articles from the last five years on PubMed with miR-136-5p as the keyword. Results: MiR-136-5p represents a class of microRNAs (miRNAs) that are involved in various human maladies, encompassing cancers, cardio-cerebrovascular disease, diabetes, inflammatory disease, tuberous sclerosis, idiopathic pulmonary fibrosis, and polycystic ovary syndrome. Altered expression of miR-136-5p in specific ailments results in downstream gene expression imbalance, influencing cellular behaviors, such as migration, proliferation, and invasion. Furthermore, miR-136-5p is implicated in five signaling pathways, where it is critical in the onset and advancement of a number of illnesses. Additionally, it has the potential to promote drug resistance to a variety of medications. Conclusion: The current review aims to elucidate the role of miR-136-5p in both cancer progression and non-cancerous disorders, emphasizing dysregulated signaling pathways. It also sheds light on the potential of this miRNA as a prognostic biomarker in cancer, offering valuable insights and directions for future research.

BACKGROUND:Insulin resistance (IR) is a key factor in the development of type 2 diabetes, and M2-like macrophages are important in maintaining normal glucose homeostasis. Our previous research has demonstrated that the total saponins from Panax japonicus (TSPJ) reduce IR in adipocytes and promote the M2 polarization of macrophages, but the molecular mechanism is unclear. PURPOSE:In the study, we aimed to elucidate whether TSPJ mitigate IR by enhancing the intercellular communication between adipocytes and macrophages and describe how the exosomes from bone marrow-derived macrophages (BMDMs) modulate the insulin sensitivity of adipocytes via miR204. METHODS:We used both in vitro and in vivo models to study the effects of TSPJ on IR, with a particular emphasis on the exosomes from M2-type BMDMs. Furthermore, we investigated the mechanisms by which exosomal miR204 and its downstream target Elovl6 influence IR in an obese mouse model, as well as in adipocytes with double inhibition of miR204 and Elovl6. RESULTS:In the animal model, TSPJ significantly increased miR204 expression in BMDMs-derived exosomes and decreased the level of Elovl6 in adipocytes. However, when the C75BL/6 mice had miR204 ablation, TSPJ became less capable of enhancing insulin sensitivity, and the expressions of Irs1, Insr, and Slc2a4 in the adipose tissue decreased. In the cell model where the macrophages carried miR204 ablation and the adipocytes had Elovl6 knockdown, the expressions of IR-related genes increased in the adipocytes. CONCLUSIONS:TSPJ mitigated IR through adipocyte-BMDM crosstalk mediated by exosomes via the miR204/Elovl6 pathway.

Introduction: Recent investigations have underscored the importance of long non-coding RNAs (lncRNAs), which exhibit more specific expression in tissues and cells than mRNA and are involved in gene regulation during development, pathology, and other processes through various mechanisms. Despite the predominant focus on the role of lncRNA Dio3os in cancer research, there has been relatively limited exploration of its potential involvement in glycolipid metabolism. Therefore, this study aims to consolidate existing knowledge on the function of Dio3os in glycolipid metabolism and calls for a broader investigation into its physiological roles. Methods: This review synthesizes available literature to detail the gene characteristics of lncRNA Dio3os and its expression patterns. It also compiles recent insights and mechanisms pertaining to Dio3os's involvement in glycolipid metabolism, particularly its participation in the ceRNA regulatory network. Results: Recent studies demonstrate that lncRNA Dio3os regulates glycolysis in cancer cells and impacts obesity, potentially serving as an indicator for diabetic peripheral neuropathy. Furthermore, its diminished expression has been noted in atherosclerotic plaques. Conclusion: lncRNA Dio3os exerts a significant regulatory influence on glycolipid metabolism, with variations in its expression levels potentially affecting disease presentations. Further investigations are warranted to elucidate the precise relationship between lncRNA Dio3os and its associated pathologies.

Background Inflammation is a key factor contributing to aging-related morbidities. Inflammation is intimately linked to the iron metabolism in macrophages, and ferritin heavy chain (Fth) is the basis of iron metabolism in macrophages. Regulating Fth to control iron metabolism may help to reduce inflammation in macrophages, which can ultimately help to alleviate certain aging-related diseases. Methods The effects of total saponins from Panax Japonicus (TSPJs) in the intervention of aging-related obesity were explored. The in vitro and in vivo models were established using RAW264.7 macrophage cells and naturally aging rats and mice. The inflammation, iron content, and gene expressions of the models were analyzed. Senescence was induced in RAW264.7 cells with adriamycin (ADR), and Fth knockdown was introduced to the models to investigate related mechanisms. Results TSPJs reduced the iron content in the macrophages and prompted M2 polarization, which affected the JNK signaling pathway (p < 0.05) and reduced the expression of inflammatory cytokines in adipose tissue. Conclusion TSPJs mediate the iron metabolism of macrophages via Fth to reduce aging-related inflammation of the adipose tissue.

In this study, the chemical components of Panacis Japonici Rhizoma extract and absorbed components in rats were identified by ultra-high performance liquid chromatography-quadrupole exactive orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS). The separation was performed by gradient elution on Waters UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) with the mobile phase of water and acetonitrile containing 0.1% formic acid. High resolution multistage mass spectrometry data were collected by electrospray ionization in positive and negative ion modes. The chemical components of Panacis Japonici Rhizoma extract were identified by comparing with the retention time, high resolution precise molecular weight, and secondary fragment ions of reference substances and related literature. After intragastric administration of Panacis Japonici Rhizoma extract, blood was collected from the abdominal aorta of rats for separation of the serum, and the absorbed components were scanned and identified. The results showed that 43 chemical components were detected in the Panacis Japonici Rhizoma extract, including 22 saponins, 9 amino acids, 5 polysaccharides, 2 volatile oils, and 5 nucleosides. In the serum, 18 components were detected, including 10 prototype components, 6 metabolites, and 2 unknown components. This study analyzed the chemical components and absorbed components of Panacis Japonici Rhizoma extract, providing clues for clarifying the pharmacological basis of Panacis Japonici Rhizoma.

Long non-coding RNA (LncRNA) refers to a large class of RNAs with over 200 nucleotides that do not have the function of encoding proteins. In recent years, more and more literature has revealed that lncRNA is involved in manipulating genes related to human health and disease, playing outstanding biological functions, which has attracted widespread attention from researchers. The newly discovered long-stranded non-coding RNA myocardial infarction-related transcript (LncRNA MIAT) is abnormally expressed in a variety of diseases, especially in diabetic complications, and has been proven to have a wide range of effects. This review article aimed to summarize the importance of LncRNA MIAT in diabetic complications, such as diabetic cardiomyopathy, diabetic nephropathy, and diabetic retinopathy, and highlight the latest findings on the pathway and mechanism of its participation in regulating diabetic complications, which may aid in finding new intervention targets for the treatment of diabetic complications. LncRNA MIAT competitively binds microRNAs to regulate gene expression as competitive endogenous RNAs. Thus, this review article has reviewed the biological function and pathogenesis of LncRNA MIAT in diabetic complications and described its role in diabetic complications. This paper will help in finding new therapeutic targets and intervention strategies for diabetes complications.

Ethnopharmacological relevenace Sertoli cells are vital to maintain spermatogenesis and their function decline during aging. Epimedium has the effects of tonifying kidney-yang, strengthening bones and muscles, and expelling wind and dampness, and is commonly used in the treatment of kidney-yang deficiency, impotence and spermatorrhea. Icariin is the main active ingredients from Epimedium exhibiting delaying aging effects and improving male reproductive dysfunction. Whereas, it remains poorly understood how icariin alleviates age-associated decline in testicular function by protecting against the damage of junction function of Sertoli cells. Aim of the study This study aimed to evaluate the improvement effect of icariin on Sertoli cell junction function damage and explore the underlying mechanisms. Materials and methods Male C57BL/6 mice and mouse Sertoli cell line TM4 cells were utilized to assess the improvement effect of icariin on aging-associated Sertoli cell junction function injury. H&E staining, transmission electron microscopy, qPCR, Western blot, molecular docking, siRNA transfection, and immunofluorescence were performed in this study. Results Dietary administration of icariin remarkly attenuated age-associated deterioration in spermatogenic function as evidenced by elevated testicular weight and index, sperm concentration and sperm viability. In addition, icariin protected Sertoli cell junction function from age-associated damage as proven by increased Sertoli cell numbers, improved tight junction ultrastructure, and upregulated junction-related proteins (ZO-1, Occludin and β-Catenin). Moreover, icariin significantly upregulated ERα/c-fos signaling and PKR pathway in testicular Sertoli cells. Similarly, in vitro studies revealed that deletion of ERα, c-fos or PKR abolished the improvement effects of icariin on Sertoli cell junction function damage. Conclusions Icariin effectively mitigates age-associated decline in testicular function by diminished Sertoli cell junction function damage through upregulating PKR pathway via ERα/c-fos signaling. Therefore, attenuating Sertoli cell junction function injury by the upregulation of PKR pathway via ERα/c-fos signaling probably indicates an effective target for the prevention and treatment of testicular spermatogenic function with aging.

Background: Panax japonicus (P. japonicus) belongs to the Panax genus of Araliaceae and is used as medicine mainly with the bamboo whiplike rhizome, which has the functions of dispelling blood stasis and hemostasis, attenuating swelling and pain, eradicating phlegm and relieving cough, tonifying, and strength. Purpose: This review intends to summarize the chemical constituents and pharmacological activities of P. japonicus to provide a scientific and systematic basis for better utilization of its rational applications. Methods: The literature was searched using PubMed, Baidu Scholar and Science Hub search engines. Results: The chemistry components isolated from P. japonicus are mainly saponins, besides also including polysaccharides, amino acids, volatile oils, inorganic elements, etc. P. japonicus exhibits extensive pharmacological activities including anti-inflammatory, antioxidant, lipid lowering activities, and therefore show extensive protective effects on the central nervous system, cardio-cerebrovascular system, digestive system. Conclusion: This article included a thorough summary of the botany, phytochemistry, and pharmacology of P. japonicus and provided evidence for its further research and clinical applications.

Background:: Long non-coding RNA (LncRNA) is a type of non-coding RNA that plays an important role in the body and accounts for the majority of RNA, and this non-coding RNA can regulate disease onset and progression with its wide range of functions. LncRNA Xist, also known as the long non-coding RNA X inactive specific transcript, is a member of them. It can regulate the development of organismal diseases by acting downstream on specific target genes. In addition to this, it can also influence disease onset and progression by acting on apoptosis, migration, invasion, and other processes. It has been shown that XIST plays an important role in the development of inflammation. Objective:: To explore the role played by XIST in inflammation-related diseases and to explore its mechanism of action. Methods:: This paper summarizes and analyzes the role played by XIST in inflammation- related diseases by conducting a search in PubMed. Conclusion:: In this paper, we summarize the mechanism of action of XIST in different types of inflammation-related diseases and propose new protocols for the future clinical treatment of these diseases.

Adipocytic lipolysis is strongly related to the increase of visceral fat, decrease of exercise capacity, and various other metabolic syndromes during aging. It is significantly influenced by the paracrine relationship between adipocytes and the adipose tissue macrophages (ATMs), and the cytokines secreted by ATMs have endocrine effects on adjacent tissues. We previously reported that the total saponins from Panax japonicus (TSPJs) can enhance lipid metabolism. In this work, we for the first time proved that TSPJs promoted adipocytic lipolysis by preventing NLRP3 activation in ATMs to inhibit the expression of GDF3. The decrease of GDF3 by TSPJs restored the expression of the adipose triglyceride lipase (ATGL) and phosphorylated hormone-sensitive lipase (p-HSL), both of which are known to decrease with aging. Thus, the NLRP3 inflammasome/GDF3/ATGL axis may be a worthy target in developing future clinical solutions for aging-related obesity.

Minor ginsenosides are a class of processed saponins with minor natural content, high bioavailability, and outstanding bio-logical activity, which are usually obtained by biological or chemical transformation of prototype saponins directly extracted from Panax plants. In recent years, with the clarification of the biosynthetic pathway of saponins and the development of synthetic biology, it has become possible to use synthetic metabolic engineering methods with microorganisms as hosts to produce saponins. Minor ginsenosides have received widespread attention because of their remarkable biological activities in enhancing the immune function of the body and antitumor property. At present, most of the reviews on minor ginsenosides focus on transformation preparation, process optimization, and pharmacological activity, but there are some deficiencies in industrial analysis. This study summarized structural types, pharmacological activities, sources of acquisition, and transformation pathways of minor ginsenosides based on the relevant literature in China and abroad, proposed problems in the preparation of existing minor ginsenosides, and discussed the future research and utilization prospects, to provide a theoretical basis for improving the basic research of minor ginsenosides and promoting their industrialization.

Aging and obesity are closely related. A key change in the adipose tissue during the aging process is the decline of lipolysis. The excitation of the sympathetic nerve system is a key pathway to promote lipolysis, but the underlying mechanism remains unclear. In this work, in vitro and in vivo aging models with and without tyrosine hydroxylase (TH) knockdown were treated with total saponins from Panax japonicus (TSPJs), and the expression of lipolysis-related proteins was examined. It was found that TSPJs could promote the expression of lipolysis-related genes and TH in adipocytes both in vitro and in vivo, and the expression of lipolysis-related genes was downregulated after TH knockdown. It was inferred that TSPJs could promote the excitation of sympathetic nerves by increasing the expression of TH in adipose tissue, which positively regulated the expression of lipases to revitalize lipolysis. The results suggested that TSPJs resisted aging-induced obesity and could be a potential medication for weight management.