Endocrine, metabolic & immune disorders drug targets最新文献

The rapidly emerging prevalence of type 2 diabetes mellitus (T2DM) and its associated complications have formed an increasingly serious threat to human life and health. Therefore, there is an urgent requirement to investigate the pathogenesis of T2DM and its complications, which will be conducive to discovering effective drugs for prevention and treatment. N6-methyladenosine (m6A) methylation is the most abundant and prevalent epigenetic modification of mRNA in mammals. m6A methylation is a dynamically reversible epigenetic transcriptome modification process that is jointly regulated by methyltransferases, demethylases and methylated reading proteins, which control the fate of target mRNAs through influencing splicing, translation and decay. Recent studies have revealed that m6A methylation plays an important role in β cellular function, insulin sensitivity and glycolipid metabolism. In this review, we summarized the current roles of m6A methylation in T2DM and T2DM-related complications such as diabetes nephropathy (DN), diabetes cardiovascular disease (DCD) and diabetes retinopathy (DR). Additionally, we sought the potential mechanism of m6A in T2DM and related complications, which may provide a rationale and strategy for potential therapeutic targeting of T2DM and its complications.

Aim: To discover new therapeutic targets for Type 2 diabetes (T2D) and develop a new diagnostic model.

Background: T2D is a chronic disease that can be controlled by oral hypoglycemic drugs, however, it cannot be fully cured. The continued increase in the prevalence of T2D and the limitations of existing treatments urgently call for the development of new drugs to be able to effectively control the progression of the disease.

Objective: We aimed to discover new therapeutic targets for T2D and to develop a new diagnostic model.

Method: Single-cell transcriptome, web-based systematic pharmacology, and transcriptology were applied to identify T2D diagnostic targets and drug candidates and to analyze the underlying molecular mechanisms.

Results: By single-cell clustering analysis, we identified seven subsets between the normal islet β-cell samples and T2D islet β-cell samples. A total of 27 key genes in the intersection of insulin- related genes and diabetes-related genes were selected by protein-protein interaction (PPI) analysis and MolecularComplexDetection (MCODE) analysis. Notably, ESR1, MME, and CCR5 had the area under curves (AUC) values as high as 67.95%, 66.67%, and 66.03% for the diagnosis of T2D, respectively. Since the expression of MME in T2D samples was significantly higher than in normal samples, we screened 155 drug candidates against MME in T2D. Finally, the molecular docking revealed a strong binding strength between MME and DB05490, which was one of the most effective candidate drugs for treating T2D.

Conclusion: Our study screens for diagnostic signatures and potential therapeutic agents for T2D, which provides valuable insights into the development of T2D biomarkers and their drug discovery.

Background: The recognition of epicardial adipose tissue (EAT) as a cardiac risk factor has increased the interest in strategies that target cardiac adipose tissue.

Aim: The effect of bariatric and metabolic surgery (BMS)-induced weight loss on EAT volume was evaluated in this study.

Methods: Fifteen bariatric patients, with (MS) or without (wMS) Metabolic Syndrome, underwent magnetic resonance imaging (MRI) using an open-bore scanner to assess EAT volume, visceral adipose tissue (VAT) thickness, and other cardiac morpho-functional parameters at baseline and 12 months after BMS. Nine patients underwent laparoscopic sleeve gastrectomy (LSG), and 6 patients underwent Roux-en-Y Gastric Bypass (RYGBP).

Results: EAT volume significantly decreased in all the patients 12 months post-BMS from 91.6 cm3 to 67.1 cm3; p = 0.0002 in diastole and from 89.4 cm3 to 68.2 cm3; p = 0.0002 in systole. No significant difference was found between the LSG and RYGBP group. Moreover, EAT volume was significantly reduced among wMS compared with MS. In particular, EAT volume in diastole was significantly reduced from 80.9 cm3 to 54.4 cm3; p = 0.0156 in wMS and from 98.3 cm3 to 79.5 cm3; p = 0.031 in MS. The reduction was also confirmed in systole from 81.2 cm3 to 54.1 cm3; p = 0.0156 in wMS and from 105.7 cm3 to 75.1 cm3; p = 0.031 in MS. Finally, a positive correlation was found between EAT loss, BMI (r = 0.52; p = 0.0443) and VAT (r = 0.66; p = 0.008) reduction after BMS.

Conclusion: These findings suggest that EAT reduction may be a fundamental element for improving the cardio-metabolic prognosis of bariatric patients. Moreover, this is the first study performed with an open-bore MRI scanner to measure EAT volume.

It is widely recognized that a strong correlation exists between metabolic diseases and chronic kidney disease (CKD). Based on bibliometric statistics, the overall number of Mendelian randomization (MR) analysis in relation to metabolic diseases and CKD has increased since 2005. In recent years, this topic has emerged as a significant area of research interest. In clinical studies, RCTs are often limited due to the intricate causal interplay between metabolic diseases and CKD, which makes it difficult to ascertain the precise etiology of these conditions definitively. In MR studies, genetic variation is incorporated as an instrumental variable (IV). They elucidate the possible causal relationships between associated risk factors and disease risks by including individual innate genetic markers. It is widely believed that MR avoids confounding and can reverse effects to the greatest extent possible. As an increasingly popular technology in the medical field, MR studies have become a popular technology in causal relationships investigation, particularly in epidemiological etiology studies. At present, MR has been widely used for the investigation of medical etiologies, drug development, and decision-making in public health. The article aims to offer insights into the causal relationship between metabolic diseases and CKD, as well as strategies for prevention and treatment, through a summary of MR-related research on these conditions.

Aims: A bibliometric study was conducted to gain deeper insights into the current state of research on diabetes and the biological clock (BC).

Methods: The study involved a comprehensive search for literature related to diabetes and BC published between 1992 and 2023 in the Web of Science database.

Results: Ninety-five articles were published in 65 journals, with six of these journals not included in the Journal Citation Reports as of 2022. Among the remaining 59 journals, 10 had an impact factor (IF) greater than 10, and 21 had an IF greater than 5. Twenty-nine journals belonged to Quartile 1, while 16 journals were part of Quartile 2. The articles were contributed by researchers from 22 countries, with the Netherlands and the USA being the most prolific contributors. However, the total number of citations for articles from the USA was significantly higher than that of the Netherlands. The co-occurrence analysis of title and abstract keywords primarily focused on investigating the mechanisms of BC. Regarding author keywords and keyword-plus, the co-occurrence analysis centered around diabetes and BC. International collaboration was prominent among developed countries, with the Netherlands, the USA, and France being major participants. Institution- wise cooperation primarily occurred between two research institutions in the Netherlands. In total, the 95 articles received 5,157 citations, averaging 54.28 citations per article.

Conclusion: To foster advancements in this area, more attention and international cooperation are necessary. Emphasizing collaborative efforts can drive the development of novel approaches to manage diabetes and regulate blood glucose levels effectively.

Background: Obesity is becoming a global pandemic with pandemic proportions. According to the WHO estimates, there were over 1.9 billion overweight individuals and over 650 million obese adults in the globe in 2016. In recent years, scientists have encountered difficulties in choosing acceptable animal models, leading to a multitude of contradicting aspects and incorrect outcomes. This review comprehensively evaluates different screening models of obesity and obesity-associated comorbidities to reveal the advantages and disadvantages/limitations of each model while also mentioning the time duration each model requires to induce obesity.

Methodology: For this review, the authors have gone through a vast number of article sources from different scientific databases, such as Google Scholar, Web of Science, Medline, and PubMed.

Results: In-vivo models used to represent a variety of obesity-inducing processes, such as diet-induced, drug-induced, surgical, chemical, stress-induced, and genetic models, are discussed. Animal cell models are examined with an emphasis on their use in understanding the molecular causes of obesity, for which we discussed in depth the important cell lines, including 3T3-L1, OP9, 3T3-F442A, and C3H10T1/2. Screening models of obesity-associated co-morbidities like diabetes, asthma, cardiovascular disorders, cancer, and polycystic ovarian syndrome (PCOS) were discussed, which provided light on the complex interactions between obesity and numerous health problems.

Conclusion: Mimicking obesity in an animal model reflects multifactorial aspects is a matter of challenge. Future studies could address the ethical issues surrounding the use of animals in obesity research as well as investigate newly developed models, such as non-mammalian models. In conclusion, improving our knowledge and management of obesity and related health problems will require ongoing assessment and improvement of study models.

Background: While the annual incidence of diabetic kidney disease (DKD) has been soaring, the exact mechanisms underlying its onset and progression remain partially understood.

Objective: The present study delved into the underlying mechanisms of Jisheng Shenqi Pill (JSP) in the treatment of DKD.

Methods: The active constituents and prospective targets of JSP were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), while DKD-associated disease targets were obtained from the GeneCards database. Subsequently, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to assess the overlapping segment of drugs and disease targets. Meanwhile, a component-target-pathway network was constructed to identify pivotal components, targets, and pathways. Molecular docking and molecular dynamics simulation were also carried out to validate the binding efficacy of the pivotal components with the targets. Finally, animal experiments were conducted to corroborate the efficacy of the aforementioned targets and pathways.

Results: According to bioinformatics analysis, the primary targets included JUN, TNF, and BAX, while the pivotal pathways involved were AGE/RAGE and PI3K/AKT signaling cascades. In vivo experiments demonstrated that JSP effectively mitigated renal impairment in DKD by reducing renal inflammation and apoptosis. This effect was presumably achieved by modulating the AGERAGE axis and the PI3K/AKT signaling pathway.

Conclusion: Our findings imply that JSP could ameliorate renal inflammation and apoptosis in DKD mice by modulating the AGE/RAGE axis and the PI3K/AKT signaling pathway. These findings provide valuable insights into traditional Chinese medicine-based treatments for DKD.

Background: Patients with permanent hypoparathyroidism experience an impaired quality of life, due to acute and chronic complications that may affect several organs, with an increased risk of hospitalisation and death. Adequate and continuous replacement therapy with calcium and calcitriol is necessary to avoid symptoms and long-term complications related to hypocalcemia.

Case presentation: A 63 years old male, affected by permanent post-surgical hypoparathyroidism, was hospitalized in the cardiology department because of a dehiscence of the subcutaneous housing of the double-chambered implantable cardioverter-defibrillator. Chronic replacement therapy for hypoparathyroidism was poorly controlled and, during hospitalization, severe hypocalcemia occurred together with electrocardiographic and echocardiogram life-threatening alterations.

Conclusion: Constant and targeted long-term replacement therapy with calcium and particularly calcitriol is necessary to avoid major consequences on patients' health, especially during acute events and in the presence of other comorbidities.

Background: International guidelines recommend a pathway for preferable nursing handling in a specific cancer topic, like chemotherapy toxicity, low adhesion in toxicity reported with a consequential increase in adverse events (AEs) frequency, poorer QoL outcomes, and increased use of healthcare service until death. Unpredictability, postponed reports, and incapability to access healthcare services can compromise toxicity-related effects by including patients' safety. In this scenario, a more attentive nursing intervention can improve patients' outcomes and decrease costs for healthcare services, respectively. The present scoping review aims to describe and synthesize scientific care nursing evidence assessment in oncology patients.

Methods: PubMed, Embase, Nursing & Allied Health Database, and British Nursing were the databases examined. Keywords used and associated with Boolean operators were assessment, care, nursing, immune disorder, oncology, and patient. Research articles considered were published between 2013-2023. All systematic processes were performed according to the PRISMA procedure in order to reach all manuscripts considered in the present scoping review.

Results: The Embase database showed a total of 25 articles, PubMed displayed 77, the Nursing & Allied Health Database evidenced a total of 74, and the British Nursing database showed 252 records. Then, after a first revision in each database by considering the inclusion criteria, the abovementioned titles and abstracts were selected and, 336 records were removed, and 92 studies remained. Of these, 65 manuscripts were excluded after verifying abstracts. Finally, a total of 7 articles were carefully analysed and selected for this scoping review. Specifically, 2 articles belonged to the British Nursing Database, 3 articles belonged to Embase, 1 to the Nursing & Allied Health Database and one related to PubMed.

Conclusion: Oncology nursing should consider several aspects, such as therapy-related toxicity and its related morbidity and mortality, worsening levels of quality of life, and increasing duty by the healthcare organization or endorsements for the principal symptoms and signs which may anticipate few diseases and worst clinical conditions, too. Therefore, careful monitoring may allow prompt recognition and subsequent earlier management in the treatment efficacy.

Introduction: Hypophysitis is an inflammatory disorder of the pituitary gland. It can manifest variously, with endocrinological and neuro-ophthalmologic symptoms and signs, due to the compression of sellar and parasellar structures.

Case representation: Although hypophysitis is rare, this pituitary disease can occur during pregnancy or in the postpartum period. In this report, we describe the case of a woman with partial hypopituitarism secondary to autoimmune hypophysitis who, five years after the diagnosis and the immunosuppressive treatment, had an uneventful pregnancy and successfully delivered a healthy infant at term.

Conclusion: We reported the clinical history of the patient and the evolution of the disease and also reviewed the management and treatment of autoimmune hypophysitis during pregnancy.