Pathogenesis and treatment of diabetes mellitus-related erectile dysfunction: current therapies and potential challenges

Erectile dysfunction(ED)is one of the important complications of diabetes,which is very common in diabetic patients,affecting more than half of male patients,and the incidence of the disease is about 3.5 times that of the normal population.The pathogenesis of diabetic erectile dysfunction(DMED)is complex,involving nerve,vascular,endocrine,muscular and psychological aspects.At present,the therapeutic approaches of DMED include drug therapy,surgery,physical therapy and so on.This article provides a review of current research on the pathogenesis and treatment of DMED.Further elucidation of the pathogenesis of DMED and the development of new therapeutic approaches are of great significance for the prevention and treatment of DMED.

Advances in the Pathogenesis and Pharmacologic Treatment of Diabetic Cataracts

Diabetic cataract(DC)is a common complication prior to diabetes mellitus,which is a metabolic disease with pathogenesis including abnormal metabolism of polyphenol pathway(PP)and non-enzymatic glycosylation(NEG)of proteins,etc.The therapeutic drugs are mainly aldose reductase inhibitors(ARIs)and glycosylation inhibitors.The therapeutic regimens for DC are becoming more and more diversified due to the development of biological testing and clinical research technology,thus improving its clinical efficacy.With the development of biological testing and clinical research technology,the treatment options for DC have become increasingly diversified and the treatment specificity has been improved,improving its clinical efficacy.In order to comprehensively analyze the pathogenesis and pharmacological treatment of this disease,the following review is made.

Role of hematological parameters in pathogenesis of diabetes mellitus:A review of the literature

Diabetes mellitus(DM)is characterized by hyperglycemia and abnormalities in insulin secretion and activity.There are numerous hematological parameters;however,this review article only focuses on red blood cells,hemoglobin,hematocrit,red blood cell indices,platelet count,white blood cells,lymphocytes,neutrophils,monocytes,eosinophils,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and monocyte-to-lymphocyte ratio,which play an essential role in the pathogenesis of DM.Also,this review article aims to report the relationship between these hematological parameters and the development of DM.In con-clusion,this article shows that increased levels of platelets,red blood cells,hematocrit,lymphocytes,eosinophils,neutrophils,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and monocyte-to-lymphocyte ratio and decreased levels of hemoglobin are involved in the pathogenesis of DM.However,the role of basophils in DM is unknown yet.

Team players in the pathogenesis of metabolic dysfunctionsassociated steatotic liver disease:The basis of development of pharmacotherapy

Nutrient metabolism is regulated by several factors.Social determinants of health with or without genetics are the primary regulator of metabolism,and an unhealthy lifestyle affects all modulators and mediators,leading to the adaptation and finally to the exhaustion of cellular functions.Hepatic steatosis is defined by presence of fat in more than 5%of hepatocytes.In hepatocytes,fat is stored as triglycerides in lipid droplet.Hepatic steatosis results from a combination of multiple intracellular processes.In a healthy individual nutrient metabolism is regulated at several steps.It ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural component.Several hormones,peptides,and genes have been described that participate in nutrient metabolism.Several enzymes participate in each nutrient metabolism as described above from ingestion to generation of ATP.As of now several publications have revealed very intricate regulation of nutrient metabolism,where most of the regulatory factors are tied to each other bidirectionally,making it difficult to comprehend chronological sequence of events.Insulin hormone is the primary regulator of all nutrients’metabolism both in prandial and fasting states.Insulin exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes;metabolic,inflammation and repair,and cell growth and regeneration.Final regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands,adiponectin,leptin,and adiponutrin.Insulin hormone has direct effect on these final modulators.Whereas blood glucose level,serum lipids,incretin hormones,bile acids in conjunction with microbiota are intermediary modulators which are controlled by lifestyle.The purpose of this review is to overview the key players in the pathogenesis of metabolic dysfunction-associated steatotic liver disease(MASLD)that help us understand the disease natural course,risk stratification,role of lifestyle and pharmacotherapy in each individual patient with MASLD to achieve personalized care and target the practice of precision medicine.PubMed and Google Scholar databases were used to identify publication related to metabolism of carbohydrate and fat in states of health and disease states;MASLD,cardiovascular disease and cancer.More than 1000 publications including original research and review papers were reviewed.

Advances in Research on the Pathogenesis of Type 2 Diabetes Complicated with Gallstone

At present, the incidence of diabetes complicated with gallstones is increasing rapidly, and there are still many problems in the pathogenesis of the disease. Diabetes complicated with gallstones is a chronic complication of diabetes, with diabetes-induced hyperinsulinemia and insulin resistance, gallbladder emptying disorders, Oddis sphincter dysfunction, gastrointestinal hormone disorders, gastrointestinal dyskinesia, fat metabolism disorders, bile Bacterial infection and other factors are related. In recent years, it has been found that in diabetic patients, Telocytes (TC) and Cajal interstitial cells (ICC) are reduced in the biliary system. In addition, the contact between ICC cells and smooth muscle cells and nerve endings is significantly reduced, so it is considered that bile Stone formation has a certain relationship with TC and ICC reduction. This article reviews recent research progress.

Research Progress on Pathogenesis and Treatment of Type 2 Diabetes Mellitus by Traditional Chinese Medicine and Western Medicine

The prevalence rate of type 2 diabetes is increasing year by year,simple surgery and Western medicine treatment has limitations,doing damage to liver and kidney function,resulting in islet function damage,insulin resistance,poor curative effect and many adverse reactions.According to the difference of patients'health conditions,traditional Chinese medicine has certain advantages in the treatment of this disease by acupuncture,auricular point treatment and prescription based on syndrome differentiation,taking replenishing qi and nourishing yin,invigorating spleen and resolving dampness as the basic principle to enhance the functions of viscera such as lung,spleen and kidney,and to strengthen the body resistance to eliminate pathogenic factors.The curative effect is remarkable and the side effect is extremely low.Therefore,this paper makes a comparative analysis of the current situation of the research on the pathogenesis and treatment of the disease between traditional Chinese medicine and Western medicine,in order to provide new ideas for clinical and scientific researchers.

Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives

Diabetic kidney disease(DKD)is one of the major chronic complications of diabetes mellitus(DM),as well as a main cause of end-stage renal disease.Over the last few years,substantial research studies have revealed a contributory role of gut microbiota in the process of DM and DKD.Metabolites of gut microbiota like lipopolysaccharide,short-chain fatty acids,and trimethylamine N-oxide are key mediators of microbial–host crosstalk.However,the underlying mechanisms of how gut microbiota influences the onset and progression of DKD are relatively unknown.Besides,strategies to remodel the composition of gut microbiota or to reduce the metabolites of microbiota have been found recently,representing a new potential remedial target for DKD.In this minireview,we will address the possible contribution of the gut microbiota in the pathogenesis of DKD and its role as a therapeutic target.

Pathogenesis of diabetic cerebral vascular disease complication

Diabetes mellitus is one of the most potent independent risk factors for the development of diabetic cerebral vascular disease(CVD). Many evidences suggested that hyperglycemia caused excess free fatty acids, the loss of endothelium-derived nitric oxide, insulin resistance, the prothrombotic state, endothelial dysfunction, the abnormal release of endothelial vasoactivators,vascular smooth muscle dysfunction, oxidative stress, and the downregulation of mi Rs participated in vessel generation and recovery as well as the balance of endotheliocytes. In turn, these abnormalities, mainly via phosphatidylinositol 3 kinase, mitogen-activated protein kinase, polyol, hexosamine, protein kinase C activation, and increased generation of advanced glycosylation end products pathway, play an important role in inducing diabetic CVD complication. A deeper comprehension of pathogenesis producing diabetic CVD could offer base for developing new therapeutic ways preventing diabetic CVD complications, therefore, in the paper we mainly reviewed present information about the possible pathogenesis of diabetic CVD complication.

One Case of Diabetes Nephropathy Stage V, Combined Valvular Disease, Total Heart Failure with Diabetes Foot Gangrene

The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was found that the color of the thumb, index and middle toe of the left foot became black. He went to a third-class hospital in Beijing and was diagnosed as “diabetes foot”. He was treated with “balloon dilation of lower limb blood vessels of diabetes foot”. Half a year ago, the third toe on the right side was broken and treated in the hospital again. “Popliteal artery stent implantation” was given for the diagnosis of “double kidney insufficiency, diabetes foot, left heart failure, combined heart valve disease”, “Hemofiltration therapy” and anti-inflammatory, amino acid supplementation, kidney function protection, anticoagulation, anemia correction and other treatments. Later, he went to our hospital and was diagnosed by the TCM diagnosis: category of consumptive disease, toe or finger gangrene (syndrome/pattern of qi and yin deficiency). Western medicine diagnosed: stage V of diabetes nephropathy, type II diabetes foot gangrene, combined with heart valve disease, hypoalbuminemia, double kidney cyst, moderate anemia, pleural effusion, hyperkalemia, pulmonary infection, and total heart failure. The patient was treated by the Qi-acupuncture therapy of TCM in combination with Chinese and Western medicine Medical treatment made the patient significantly better and discharged.

Single-cell sequencing technology in diabetic wound healing:New insights into the progenitors-based repair strategies

Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding the pathogenesis of diabetic wounds,the underlying mechanisms remain unclear.The advent of single-cell RNA sequencing(scRNAseq)has revolutionised biological research by enabling the identification of novel cell types,the discovery of cellular markers,the analysis of gene expression patterns and the prediction of develop-mental trajectories.This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels.In this editorial,we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing.ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for inter-vention,offering hope for improved patient outcomes in the management of this challenging complication of DM.

Integrated data mining and network pharmacology to discover a novel traditional Chinese medicine prescription against diabetic retinopathy and reveal its mechanism

Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.

TCM diagnosis and treatment theory of chronic complete occlusion of coronary artery based on etiology and pathogenesis

Chronic total occlusive disease of the coronary artery belongs to the category of"chest palsy"and"true heart pain"in traditional Chinese medicine.Its etiology has two aspects:deficiency of blood,blood stasis,qi stagnation,and phlegm.Failure can be caused by deficiency or disease.The pathogenesis of this disease is caused by obstruction of the heart pulse,and its pathogenesis can be transformed into each other.The theory of traditional Chinese medicine believes that the general rule is not painful.Therefore,the treatment of coronary CTO lesions should be based on the combination of Tong and Tong tonic.The chronic complete occlusive disease of the coronary artery can be treated through Xuanbi Tongyang,Huoxue Tongluo,and Aroma Wentong.Based on the Chinese medicine's understanding of the etiology and pathogenesis of coronary CTO lesions,it provides a basis for the diagnosis and treatment of traditional Chinese medicine,solves the problems of interventional medicine in western medicine,and gives play to the unique advantages of traditional Chinese medicine for clinical diagnosis and treatment.

Mechanism of sex hormone level in biological clock disorder induced acne and analysis of TCM Pathogenesis

Acne vulgaris is a common chronic inflammatory disease of pilosebaceous units. And sex hormone level disorder has became a hot research topic in the pathogenesis of acne. Studies show that the biological clock disorder can result in the disorder of sex hormone levels which causes or aggravates acne. Biological clock disorder coincides naturally with "sleep rhythm disorder" in Traditional Chinese Medicine(TCM). In this paper, we will discuss the modern medical mechanism of the biological clock disorder resulting in acne from the angle of sex hormones, and analyze the TCM pathogenesis of the disease caused by the disorder of the biological clock.

Mitochondrial energy metabolism in diabetic cardiomyopathy:Physiological adaption,pathogenesis,and therapeutic targets

Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes,which could eventually develop heart failure and leads to the death of the patients.Although blood glucose control and medications to heart failure show beneficial effects on this disease,there is currently no specific treatment for diabetic cardiomyopathy.Over the past few decades,the pathophysiology of diabetic cardiomyopathy has been extensively studied,and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target.In this review,we summarize the latest research in the field of diabetic cardiomyopathy,focusing on mitochondrial damage and adaptation,altered energy substrates,and potential therapeutic targets.A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

Hepatitis C virus(HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus(T1DM) and T2 DM. T2 DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1 DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2 DM and chronic hepatitis C(CHC) infection. The processes through which CHC is associated with T2 DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immunemediated mechanisms. Few data have been reported on the association of CHC and T1 DM and reports on the potential association between T1 DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoim-munity and in certain cases lead to the development of T1 DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with nondiabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effec-tive programmes for the surveillance and treatment of diabetic CHC patients.

Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment

Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2diabetes are at a particularly high risk for developing the progressive forms of NAFLD,non-alcoholic steatohepatitis and associated advanced liver fibrosis.Moreover,diabetes is an independent risk factor for NAFLD progression,and for hepatocellular carcinoma development and liver-related mortality in prospective studies.Notwithstanding,patients with NAFLD have an elevated prevalence of prediabetes.Recent studies have shown that NAFLD presence predicts the development of type2 diabetes.Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients.The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods,although histopathological evaluation is still considered the gold standard diagnostic method.An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking.We sought to outline the published data including epidemiology,pathogenesis,diagnosis and treatment of NAFLD in diabetic patients,in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

Enterovirus and type 1 diabetes: What is the matter?

A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus(T1DM) establishment. Environmental factors may initiate and possibly sustain, accelerate, or retard damage to β-cells. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of human enterovirus in the pathogenesis of T1 DM. The genetic risk of T1 DM and particular innate and acquired immune responses to enterovirus infection contribute to a tolerance to T1DM-related autoantigens. However, the frequency, mechanisms, and pathways of virally induced autoimmunity and β-cell destruction in T1 DM remain to be determined. It is difficult to investigate the role of enterovirus infection in T1 DM because of several concomitant mechanisms by which the virus damages pancreatic β-cells, which, consequently, may lead to T1 DM establishment. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective.

Prognostic value of endothelial dysfunction in type 1 diabetes mellitus

Patients with diabetes mellitus are at high risk of developing atherosclerosis, associated with higher rates of micro and macro vascular involvement such as coronary artery disease and renal disease. The role of hyperglycemia to induce synthesis of reactive oxygen species by the oxidation of glucose, leading to an increased production of advanced glycosylation end products, as well as inflammation and oxidative stress has been proposed as a possible mechanism in the pathogenesis of endothelial dysfunction(ED). The interaction between C-peptide- the connecting segment of pro-insulin-and nitric oxide in vasodilation is also discussed. Therefore, endothelial dysfunction has been identified as an early marker of vascular disorder in type 1 and type 2 diabetes mellitus. In some other diseases, ED has been considered an independent predictor of vascular disease, regardless of the method used. Studies have demonstrated the importance of endothelial dysfunction as an useful tool for identifying the risk of vascular complications in patients with type 1 diabetes mellitus, particularly as regards to renal impairment. The aim of this review is to clarify the prognostic value of endothelial dysfunction as a marker of vascular disease in these subjects.

Oxidative stress and antioxidants in diabetes mellitus

Numerous studies have implicated oxidative stress in the development of complications of diabetes.During hyperglycemia,production of oxidant agents such as reactive oxygen species and reactive nitrogen species increases.This process,along with a decrease in the activity of antioxidant enzymes,induces oxidative stress in the body.This redox imbalance causes damage to vital biomolecules such as proteins,lipids and DNA and results in the generation of harmful products for the body.Mechanisms associated with the creation of oxidative stress conditions and subsequently complications of diabetes are explained through several pathways such as flux through the polyol pathway,intracellular production of advanced glycation end products precursors,protein kinase-C activation,and increased activities of the hexosamine pathway.On the other hand,the study of polymorphism in the antioxidant enzymes genes indicates that some of the gene polymorphisms reduce the antioxidant power of the enzymes.This article aims to review various studies to demonstrate the effect of oxidative stress on the pathogenesis of diabetes and the positive role of antioxidants on diabetic complications.

TCM Stage Differentiation Treatment of Diabetic Gangrene——An Observation on Microcirculatory Changes

Microcirculatory changes and therapeutic effects in 39 non-insulin dependent diabetes mellitus (NIDDM) cases were evaluated. Under the same basic treatment in both groups, the treatment group (21 cases) was treated with TCM drugs according to its stages and compared with the control group (18 cases, treated with 654-2). The results showed that the microcirculatory cumulative scores were significantly decreased in both groups (P<0.05), but the decrease in the treatment group was more marked (P<0.05). In the treatment group, 15 cases were cured, 3 markedly effective, 2 effective and 1 ineffective; while in the control group, 13 cases were cured, 1 markedly effective and 4 ineffective. Statistically, there is no significant difference between the 2 groups (P>0.05) in therapeutic effects.