Research progress of traditional Chinese medicine in the treatment of endocrine metabolic diseases in 2023

This study aimed to provide a comprehensive review of the research progress in Chinese medicine in the treatment of endocrine metabolic diseases in 2023,covering traditional Chinese medicine(TCM)monomers,TCM extracts,and TCM combinations,including non-alcoholic fatty liver disease,type 2 diabetes mellitus and its complications,obesity,hyperuricaemia,and thyroid disorders.After systematic sorting and summary,we found that in 2023,the research focusing on the application of TCM for endocrine metabolic diseases was still on the mechanism of action at the cellular and molecular levels,which not only influenced the classical pathways of lipid metabolism,but also delved into the key mechanisms of anti-inflammation,anti-oxidation,anti-insulin resistance,and so on.Additionally,TCM has shown remarkable results in the treatment of endocrine metabolic diseases by improving intestinal flora disorders and abnormal cellular iron death.These research results provide valuable ideas,methods,and tools for TCM in the prevention and treatment of endocrine metabolic diseases,and provide important references and guidance for future research and practice.

The role of FMO3 in metabolic diseases

Flavin containing monooxygenase 3(FMO3)is a member of the flavin monooxygenase family,which can oxidize the precursor Trimethylamine(TMA)provided from food to produce Trimethylamine N-oxide(TMAO).The autosomal recessive inherited disease caused by partial functional loss of Fmo3 gene,which leads to excessive excretion of TMA in body fluids and emits fishy odor,is called Fish Odor Syndrome or Trimethylaminuria.This disease has been documented for 3,000 years ago and was first reported in the case report in 1970.FMO3 mainly exists in the liver and can participate in the TMA-TMAO metabolic balance in intestinal microorganisms,liver,and kidneys,closely related to insulin resistance,diabetes,cholesterol metabolism,and cardiovascular disease.Due to its wide range of catalytic substrates and low susceptibility to metabolite accumulation,its role in drug metabolism,new drug development,and discovery of new drug targets are increasingly valued.This review will summarize the research progress on the metabolic process and localization of FMO3,congenital genetic defects,metabolic diseases,and its related possible mechanisms.

Infrared thermography in metabolic diseases

The prevalence of metabolic diseases,some diseases that are seriously harmful for human health and affect the quality of life,is increasing year by year.Early detection and intervention is the common strategy to deal with them.Infrared thermography(IRT)is a special medical imaging technology which can capture the changes of skin temperature associated with metabolic disorders.It might be a new method for early detection of metabolic diseases.The purpose of this review is to summarize advances of the use of IRT in evaluating single metabolic disorder such as obesity,hyperglycemia and hypertension,complex metabolic disorders such as metabolic syndrome and target organ damage such as coronary artery atherosclerosis and diabetic foot.The characteristic of thermograms of metabolic disease patients,the changes of thermal maps during the development of the disease,and the lacks in current studies are also discussed in the article.

Application of medium-chain fatty acids in metabolic diseases

Medium-chain fatty acids(MCFAs),which are important dietary fats,can be rapidly metabolized to efficiently produce a high amount of energy owing to their unique transportation system.MCFAs have thus become high-value functional foods.MCFAs also have antibac-terial and immunoregulatory effects,help to maintain intestinal health,and have shown benefits for disease prevention and treatment.Therefore,they have the potential to be used for a variety of purposes.We herein describe the metabolic pathways involving MCFAs and their main biological functions in the human body.In addition,the effects of MCFAs as adjuvant therapy for different diseases,such as obesity,polycystic ovary syndrome,sarcopenia,and malignancy are summarized,and the likely mechanisms of action are discussed.Finally,we describe possible future clinical applications of MCFAs in the field of metabolic diseases.

Research Progress on Metabolic Diseases in Rural Areas

Through the review of relevant literature in recent years,it is found that the incidence rate of metabolic diseases in rural areas is on the rise:The related factors that may cause diseases include diet structure,exercise habits,medical resources and other aspects.At the same time,there are some limitations in the intervention and treatment measures of this kind of disease.It is urgent to carry out in-depth exploration for the special conditions in rural areas.By reviewing the research progress related to metabolic diseases in rural areas,more new ideas are provided for the treatment and improvement of metabolic diseases in rural areas.

PPARs： diverse regulators in energy metabolism and metabolic diseases

The nuclear receptor PPARs are fundamentally important for energy homeostasis. Through their distinct yet overlapping functions and tissue distribution, the PPARs regulate many aspects of energy metabolism at the transcriptional level. Functional impairment or dysregulation of these receptors leads to a variety of metabolic diseases, while their ligands offer many metabolic benefits. Studies of these receptors have advanced our knowledge of the transcriptional basis of energy metabolism and helped us understand the pathogenic mechanisms of metabolic syndrome.

Fecal microbiota transplantation in the metabolic diseases:Current status and perspectives

With the development of microbiology and metabolomics,the relationship between the intestinal microbiome and intestinal diseases has been revealed.Fecal microbiota transplantation(FMT),as a new treatment method,can affect the course of many chronic diseases such as metabolic syndrome,malignant tumor,autoimmune disease and nervous system disease.Although the mechanism of action of FMT is now well understood,there is some controversy in metabolic diseases,so its clinical application may be limited.Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection,and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases.However,the initial results are varied,suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT.The success of FMT depends on the microbial diversity and composition of donor feces.Therefore,clinical trials may fail due to the selection of ineffective donors,and not to faulty indication selection for FMT.A new understanding is that FMT not only improves insulin sensitivity,but may also alter the natural course of type 1 diabetes by modulating autoimmunity.In this review,we focus on the main mechanisms and deficiencies of FMT,and explore the optimal design of FMT research,especially in the field of cardiometabolic diseases.

Progress on haptoglobin and metabolic diseases

Haptoglobin(Hp)is an acidic glycoprotein,existing in the serum and other body fluids of human beings and a variety of mammals.Hp is produced in the liver,white adipose tissue,and the kidney.The genetic polymorphisms and different phenotypes of Hp have different biological functions.Hp has antibacterial,antioxidant,and angiogenic effects and is associated with multiple diseases including simple obesity,vascular complications of diabetes mellitus,nonalcoholic fatty liver disease,hypertension,blood diseases,autoimmune diseases,and malignant tumors.Hp also participates in many life activities,indicating the importance of Hp in further studies.Previously,we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials.However,the specific mechanism of Hp in patients with simple obesity is still unclear.The purpose of this article is to introduce recent research progress on Hp,emphasizing the relationship between Hp and the development of metabolic disease,which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.

The Role of CARD9 in Metabolic Diseases

Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).This elicits initiation of the pro・inflammatory cytokines and leads to inflammatory responses,which has been recognized as a critical contributor to chronic inflammation.Current researches demonstrate that CARD9 is strongly associated with metabolic diseases,such as obesity,insulin resistance,atherosclerosis and so on.In this review,we summarize CARD9 signaling pathway and the role of CARD9 in metabolic diseases.

Gut Microbiota and Metabolic Diseases

In this review, the characteristics of gut microbiota changes in 11 metabolic diseases, as well as the research progress on their interventions, are summarized. The gut microbiota contributes to metabolic diseases through intestinal mucosal dysfunction, chronic metabolic inflammatory response, gut brain axis imbalance, gene regulation, insulin resistance, and the action of its metabolites. The researches of cause effect relationship and mechanism are relatively few, need further study, expecting a breakthrough in the future to be a new path in the treatment of some metabolic diseases.

Research progress on the correlation between metabolic-associated fatty liver disease and metabolic diseases

Metabolic-associated fatty liver disease(MAFLD)is a positive diagnostic criterion and metabolic dysfunction is listed as an important cause of hepatic liver disease.MAFLD is a liver manifestation of metabolic syndrome and a key driver of metabolic syndrome.Glucose and lipid metabolism are disordered in MAFLD,which leads to extrahepatic complications through cytokines,genetic variation,visceral fat accumulation,dietary intake,and complex intestinal microbiome.Extensive clinical evidence suggests that MAFLD is independently associated with various metabolic diseases.With its renaming,the epidemiology,pathogenesis,and treatment of MAFLD and metabolic-related diseases need to be reassessed and studied to lay out a foundation for effective prevention and treatment strategies in the future.

Integration of multi-omics in investigations on the mechanisms of action of Chinese herbal medicine interventions in metabolic diseases

The rapid development of bioinformatics has provided novel approaches and methods for exploring the mechanisms of disease treatment via Chinese herbal medicines.Compound Chinese herbal medicines formulas have complex compositions and are characterized by their multiple constituents and diverse array of biological targets.Therefore,the mechanisms of action of most compound Chinese herbal medicines formulas cannot be adequately explained using a single pathway.Omics technologies describe high-throughput-based analytical and detection techniques,which include transcriptomics,proteomics,and metabolomics and provide multilayer parameter information that can be integrated to characterize the overall relationships involved in the therapeutic effects of Chinese herbal medicines formulas.Through their combination with network biology and drug effect networks,omics technologies also enable investigations into the mechanisms of disease treatment in traditional Chinese medicine.The integration of multiple omics technologies is in line with the concept of holism in traditional Chinese medicine and provides an approach for combining modern science and technology with traditional Chinese medicine theories.In recent years,omics technologies have been widely used to elucidate the mechanisms of action of Chinese herbal medicines.The latest studies employing multi-omics integration for investigating the mechanisms of action of Chinese herbal medicines interventions in metabolic diseases have devoted greater attention to in-depth explorations of disease pathogenesis.This paper provides a review of the following multi-omics technologies,which are used in research on the treatment of common metabolic diseases(e.g.,type-2 diabetes mellitus,nonalcoholic fatty liver disease):network pharmacology combined with metabolomics,16S rRNA sequencing combined with transcriptomics,16S rRNA sequencing combined with metabolomics,and 16S rRNA sequencing combined with network pharmacology and metabolomics.

Research progress of peroxisome proliferator-activated receptor α in metabolic diseases

Peroxisome proliferator-activated receptorα(PPAR-α)is a transcription factor activated by ligand receptors and is a subfamily of the nuclear receptor superfamily.The PPAR subfamily consists of three subtypes:PPAR-α(NR1C1),PPAR-β/δ(NR1C2)and PPAR-γ(NR1C3).Among them,PPAR-αis the first discovered transcription factor and the main regulator of fatty acid oxidation homeostasis.Some natural and synthetic ligands can activate PPAR-α,and the activation of PPAR-αthrough its ligands can modify many of the cells in the cell.Biological processes,these processes are closely related to the energy metabolism mechanism of metabolic diseases,so it represents an important molecular target for the development of new drugs for the treatment of metabolic diseases.The following summarizes the latest progress of PPAR-αand energy metabolism in terms of the structure and distribution of PPAR-α,its role in different tissues,and its role in metabolic diseases,etc.,providing a theoretical basis for the prevention and treatment of metabolic diseases.

Dysregulated bile acid homeostasis:unveiling its role in metabolic diseases

Maintaining bile acid homeostasis is essential for metabolic health.Bile acid homeostasis encompasses a complex interplay between biosynthesis,conjugation,secretion,and reabsorption.Beyond their vital role in digestion and absorption of lipid-soluble nutrients,bile acids are pivotal in systemic metabolic regulation.Recent studies have linked bile acid dysregulation to the pathogenesis of metabolic diseases,including obesity,type 2 diabetes melli-tus(T2DM),and metabolic dysfunction-associated steatotic liver disease(MASLD).Bile acids are essential signaling molecules that regulate many critical biological processes,including lipid metabolism,energy expenditure,insulin sensitivity,and glucose metabolism.Disruption in bile acid homeostasis contributes to metabolic disease via altered bile acid feedback mechanisms,hormonal dysregu-lation,interactions with the gut microbiota,and changes in the expression and function of bile acid transporters and receptors.This review summarized the essential molecular pathways and regulatory mechanisms through which bile acid dysregulation contributes to the pathogenesis and progression of obesity,T2DM,and MASLD.We aim to underscore the significance of bile acids as potential diag-nostic markers and therapeutic agents in the context of metabolic diseases,providing insights into their application in translational medicine.

Immune remodulation in pediatric inherited metabolic liver diseases

Inherited metabolic liver diseases arise from genetic mutations that lead to dis-ruptions in liver metabolic pathways and are predominantly observed in pedia-tric populations.The spectrum of genetic metabolic liver disorders is diverse,encompassing a range of conditions associated with aberrations in iron,copper,carbohydrate,lipid,protein,and amino acid metabolism.Historically,research in the domain of genetic metabolic liver diseases has predominantly concentrated on hepatic parenchymal cell alterations.Nevertheless,emerging studies suggest that inherited metabolic liver diseases exert significant influences on the immune microenvironment,both within the liver and systemically.This review endeavors to encapsulate the immunological features of genetic metabolic liver diseases,aiming to expand the horizons of researchers in this discipline,and to elucidate the underlying pathophysiological mechanisms pertinent to hereditary metabolic liver diseases and to propose innovative therapeutic approaches.

Clinical relevance of circulating non-coding RNAs in metabolic diseases:Emphasis on obesity,diabetes,cardiovascular diseases and metabolic syndrome

Non-coding RNAs(ncRNAs)participate in the regulation of several cellular processes including transcription,RNA processing and genome rearrangement.The aberrant expression of ncRNAs is associated with several pathological conditions.In this review,we focused on recent information to elucidate the role of various regulatory ncRNAs i.e.,micro RNAs(miRNAs),circular RNAs(circRNAs)and long-chain non-coding RNAs(lncRNAs),in metabolic diseases,e.g.,obesity,diabetes mellitus(DM),cardiovascular diseases(CVD)and metabolic syndrome(MetS).The mechanisms by which ncRNAs participated in disease pathophysiology were also highlighted.miRNAs regulate the expression of genes at transcriptional and translational levels.circRNAs modulate the regulation of gene expression via miRNA sponging activity,interacting with RNA binding protein and polymerase II transcription regulation.lncRNAs regulate the expression of genes by acting as a protein decoy,miRNA sponging,miRNA host gene,binding to miRNA response elements(MRE)and the recruitment of transcriptional element or chromatin modifiers.We examined the role of ncRNAs in the disease pathogenesis and their potential role as molecular markers for diagnosis,prognosis and therapeutic targets.We showed the involvement of ncRNAs in the onset of obesity and its progression to MetS and CVD.miRNA-192,miRNA-122,and miRNA-221 were dysregulated in all these metabolic diseases.Other ncRNAs,implicated in at least three diseases include miRNA-15a,miRNA-26,miRNA-27a,miRNA-320,and miRNA-375.Dysregulation of ncRNAs increased the risk of development of DM and MetS and its progression to CVD in obese individuals.Hence,these molecules are potential targets to arrest or delay the progression of metabolic diseases.

Long noncoding RNA(lncRNA)H19:An essential developmental regulator with expanding roles in cancer,stem cell differentiation,and metabolic diseases

Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

The hippo kinases MST1/2 in cardiovascular and metabolic diseases:A promising therapeutic target option for pharmacotherapy

Cardiovascular diseases(CVDs)and metabolic disorders are major components of noncommunicable diseases,causing an enormous health and economic burden worldwide.There are common risk factors and developmental mechanisms among them,indicating the far-reaching significance in exploring the corresponding therapeutic targets.MST1/2 kinases are well-established proapoptotic effectors that also bidirectionally regulate autophagic activity.Recent studies have demonstrated that MST1/2 influence the outcome of cardiovascular and metabolic diseases by regulating immune inflammation.In addition,drug development against them is in full swing.In this review,we mainly describe the roles and mechanisms of MST1/2 in apoptosis and autophagy in cardiovascular and metabolic events as well as emphasis on the existing evidence for their involvement in immune inflammation.Moreover,we summarize the latest progress of pharmacotherapy targeting MST1/2 and propose a new mode of drug combination therapy,which may be beneficial to seek more effective strategies to prevent and treat CVDs and metabolic disorders.

Update on the gut microbiome in health and diseases

The Human Microbiome Project,Earth Microbiome Project,and next-generation sequencing have advanced novel genome association,host genetic linkages,and pathogen identification.The microbiome is the sum of the microbes,their genetic information,and their ecological niche.This study will describe how millions of bacteria in the gut affect the human body in health and disease.The gut microbiome changes in relation with age,with an increase in Bacteroidetes and Firmicutes.Host and environmental factors affecting the gut microbiome are diet,drugs,age,smoking,exercise,and host genetics.In addition,changes in the gut microbiome may affect the local gut immune system and systemic immune system.In this study,we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases.Due to the high number of publications on the argument,from a methodologically point of view,we decided to select the best papers published in referred journals in the last 3 years.Then we selected the previously published papers.The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.