Endocrine, metabolic & immune disorders drug targets最新文献

Background: Associative learning deficits are constantly found in subclinical hypothyroidism (SCH). Despite achieving normal thyroid stimulating hormone (TSH) levels, a considerable number of patients undergoing levothyroxine (LT-4) treatment frequently complain about memory retrieval. The Paired Association Learning (PAL) task involves computerised testing on the CANTAB- Cambridge Neuropsychological Test Automated Battery, also considered a screening tool for Alzheimer's disease (AD).

Purpose: This study aimed to investigate the impact of different levels of TSH on visual associative learning in SCH and determine if these impairments were reversed with LT-4.

Methods: A total of 134 participants were included in this cross-sectional study. Group 1: 35 healthy controls; patients with SCH (Group 2: 33 newly identified cases; Group 3: 32 patients on LT-4 with elevated TSH; Group 4: 34 euthyroid but on LT-4). A thyroid profile and a neuropsychological clinical assessment were done. The visual PAL task was performed on CANTAB.

Results: PAL was significantly impaired (p = <0.05) in all 3 patient groups as compared to Group 1. The PAL total errors (adjusted) scores were significantly higher in Groups 2 and 3, indicating that associative learning is definitely impaired in SCH, reaching levels previously seen in patients with AD.

Conclusion: Our findings encourage screening for visual associative learning or memory retrieval in patients with SCH. The study present has established a more reasonable threshold of TSH 2.5mIU/L to encourage examination of associative learning and the initiation of LT-4 in SCH. Poor PAL task performance in patients with SCH may have significant implications in clinical settings for suspecting AD.

Objective: This study employs a network meta-analysis method to investigate the clinical effectiveness of acupuncture in patients with polycystic ovary syndrome (PCOS) experiencing infertility.

Methods: Prospective randomized controlled trials (RCTs) of clomiphene citrate (CC) and letrozole (LE) combined with acupuncture in PCOS infertility patients were identified through computerized searches in databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chongqing VIP Database. The search period was set from inception until August 1, 2023, with no language restrictions. Two researchers screened articles, extracted data, and independently assessed the risk of bias in eligible trials. Data were analyzed and visualized using the R software gemtc package. With patients with medication treatment only set as controls, a meta-analysis was performed to investigate the difference in the pregnancy outcomes of the PCOS patients following medication amalgamated with different acupuncture treatments, namely, manual acupuncture (MA), electroacupuncture (EA), and warm acupuncture (WA).

Results: The serum concentrations of follicle-stimulating hormone (FSH) did not exhibit significant changes following acupuncture treatments. Notably, acupuncture-based medication treatment significantly reduced serum levels of luteinizing hormone (LH) and elevated the testosterone (T) concentrations of patients when compared to medication treatment alone. Patients also showed significantly escalated serum estradiol (E2) levels after receiving CC integrated with acupuncture than those given monotherapy of CC. The combined regimen of medication and acupuncture appeared to improve the pregnancy outcomes compared to the monotherapy of medication, as evidenced by the significantly increased success rate of pregnancy. Furthermore, the treatment combination of CC plus WA and LE plus MA yielded the highest probability of achieving the best pregnancy outcomes.

Conclusion: For PCOS infertility patients, acupuncture, as a complementary treatment to CC and LE, holds advantages in improving reproductive hormone levels and enhancing pregnancy success rates. The highest probability of achieving the best pregnancy outcomes is associated with the treatment combination of CC with WA and LE with MA.

Background: Resistance to thyroid hormone is a rare syndrome characterized by peripheral resistance to thyroid hormones. It is caused by genetic dysfunction of thyroid receptor genes, with Thyroid hormone Receptor-beta (TRβ) being the most prevalent. Affected patients show high thyroid hormone levels and non-suppressed Thyroid-stimulating Hormone (TSH). Syndrome manifestations vary from hyperthyroidism to hypothyroidism depending on the specific mutation.

Case presentation: We, herein, describe the case of a 24-year-old female with a diagnosis of resistance to thyroid hormone from the age of 7. The main symptoms the patients complained about were headaches, palpitations, hyperidrosis, and frequent evacuations with severe underweight. The patient's blood test showed high FT3 and FT4 levels with a non-suppressed TSH. We performed a disease complications screening that revealed mild osteoporosis and normal cardiac activity (the patient was already treated with bisoprolol).

Conclusion: This case illustrates symptoms and complications of resistance to thyroid hormone syndrome, a rare and misdiagnosed condition. In this case report, we describe and explain longterm disease symptoms and their management. The long-term history of our patient's disease adds a more comprehensive evaluation of the syndrome and its consequences, contributing to new insights into the resistance to thyroid hormone syndrome and shedding light on personalized management of its manifestations.

Objective: The objective of this study was to examine the impact of "Tianyu" Pairing on oxidative stress in the development of Rheumatoid arthritis (RA) and approach its potential mechanism using cell experiments.

Methods: A cell model of RA was developed by stimulating rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) with tumor necrosis factor-α (TNF-α). This model aimed to assess the impact of serum containing Rhodiola rosea-Euonymus alatus drug pair (TYP) on inflammation and oxidative stress in the development of RA, specifically through the Keap1/Nrf2/HO-1 pathway.

Results: The findings from the in vitro experiment demonstrated that the presence of TYP in the serum effectively suppressed the proliferation of RA-FLS induced by TNF-α. Additionally, TYP facilitated the apoptosis of afflicted cells, attenuated the migratory and invasive capabilities of diseased cells, and decreased the levels of Kelch ECH associating protein 1 (Keap1), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) (p < 0.01). The influence of inflammation and oxidative stress in RA-FLS cells was reduced by increasing the nuclear-cytoplasmic ratio of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and levels of phosphorylated Nrf2, Heme Oxygenase 1 (HO-1), and Superoxide Dismutase (SOD) (p < 0.01).

Conclusion: TYP can regulate inflammation and oxidative stress in RA-FLS cells by activating the Keap1/Nrf2/HO-1 pathway.

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.