Endocrine, metabolic & immune disorders drug targets最新文献

Background: Autoimmunity can be the first or predominant manifestation in patients with primary immunodeficiency disorder, also known as inborn errors of immunity (IEI). This study aims to evaluate the immune status of pediatric patients with polyautoimmunity to identify those with underlying immune defects.

Methods: In this cross-sectional study, pediatric patients with polyautoimmunity including at least one confirmed autoimmune endocrine disease were enrolled. Demographic and clinical data were collected using a questionnaire based on medical records and direct family interviews. For each patient, a basic immunologic evaluation was performed. The clinical diagnosis was established according to the criteria of the European Society for Immunodeficiencies (ESID). Based on the presence or absence of a history of severe and/or recurrent infections, patients were divided into two groups for comparison.

Results: Thirty-nine patients, 18 males (46.2%) and 21 females (53.8%), were included. Fourteen patients (35.9%) had consanguineous parents. Fifteen patients (38.5%) had a history of severe and/or recurrent infections. The median (interquartile range: IQR) age of our patients at the time of evaluation was 11.1 (9-16) years. The median (IQR) age at the onset of infections and autoimmunities were 3 (1-10.8) and 5 (2.6-8) years, respectively. The most common infectious complications reported were pneumonia and candidiasis, each in 12.8% of the patients. The most prevalent autoimmune disorders were type 1 diabetes (74.3%) and autoimmune thyroiditis (58.9%). IEI was diagnosed in six patients (15.38%), five of which were from the group with severe or recurrent infections: three with selective IgA deficiency, two with common variable immunodeficiency (CVID), and one with immune dysregulation, polyendocrinopathy, enteropathy, Xlinked (IPEX), but without a history of infections.

Conclusion: The occurrence of early onset polyautoimmunity in association with severe and/or recurrent infections or in patients with a positive family history should be a warning sign for physicians to initiate an evaluation for possible immunodeficiency disorders to prevent complications through early treatment.

Over 100-1000 microbial species reside in the human gut, where they predominantly influence the host's internal environment and, thus, have a significant impact on host health. Probiotics are best characterized as a microbe or a group of microbes that reside in the gut and support the body's internal microbiota. Probiotics are linked to increased health advantages, including better immune function, improved nutritional absorption, and protection against cancer and heart-related illnesses. Several studies have demonstrated that combining probiotics from different strains with complementary activities may have synergistic advantages and aid in re-establishing the equilibrium of how immunological niches and microorganisms interact. Another thing to remember is that even though a product contains more probiotic strains, that doesn't always guarantee that the health benefits will be more significant. For specific combinations to be justified, there must be clinical proof. The clinical results of a probiotic strain are specifically pertinent to the participants in the relevant research, such as studies on adults or newborn infants. Clinical outcomes of a probiotic strain are mainly connected to the investigated health area (such as gut health, immune health, oral health, etc.). As a result, picking the right probiotic is essential yet tricky because of several factors, including probiotic products with the disease and strain-specific effectiveness exists; however, various probiotic strains have diverse modes of action. The current review focuses on probiotic categorization, their function in enhancing human health, and any potential health benefits of probiotic combinations.

Background: Early detection and resection of colorectal polyps by routine colonoscopy screening can be effective in reducing the risk of colorectal cancer (CRC).

Objective: This study aimed to determine the association between diabetes mellitus (DM) and different types of colorectal polyps in the Chinese population.

Methods: A retrospective analysis was performed on inpatients admitted to the Gastroenterology Department of our hospital from January to December 2019. Clinical data, and colonoscopy and pathology findings of the subjects were collected. Bivariate analysis was used to assess factors associated with colorectal polyps. Significant variables from the bivariate evaluation were included in a stepwise multivariate logistic regression analysis to recognize independent predictors of neoplastic polyps and high-risk adenomas.

Results: The proportion of patients with DM was significantly higher in patients with neoplastic polyps and high-risk adenomas than in patients without polyps. Age ≥ 50 years, male gender, and a first-degree relative with a history of CRC were independent risk factors for neoplastic polyps and high-risk adenomas, even in non-smokers. An independent risk factor analysis that did not include a family history of CRC showed that age, gender, and alcohol consumption were independent risk factors for neoplastic polyps and high-risk adenomas. DM was an independent risk factor for high-risk adenomas (OR = 2.902, 95% CI = 1.221-6.899; p = 0.016) after adjusting for age, gender, alcohol consumption, and body mass index. Thus, a history of DM significantly increases the risk of high-risk adenomas.

Conclusion: This study demonstrated that patients with DM, age ≥ 50 years, male gender, alcohol consumption, and a first-degree relative with a history of CRC should undergo regular endoscopic screening and colonic polypectomy.

Diabetes is a metabolic disorder that has been reported to increase the mortality rate worldwide. About 40 million people across the globe suffer from diabetes, with people living in developing countries being affected the most due to this deadly disease. Although the therapeutic management of hyperglycaemia can treat diabetes, metabolic disorders associated with this disease are a greater challenge in its treatment. Hence, potential strategies to treat hyperglycaemia and its side effects are needed. In this review, we have summarized several therapeutic targets, like dipeptidyl peptidase-4 (DPP-4), glucagon receptor antagonists, glycogen phosphorylase or fructose-1,6- biphosphatase inhibitors, SGLT inhibitors, 11beta-HSD-1 inhibitors, glucocorticoids receptor antagonists, glucose-6-phosphatase and glycogen phosphorylase inhibitors. These targets can help in designing and developing novel antidiabetic agents.

Background: Congenital amegakaryocytic thrombocytopenia (CAMT) is a bone marrow failure syndrome with autosomal recessive inheritance characterized by the lack of megakaryocytes and thrombocytopenia. The cause of the disease is a mutation in the c-Mpl gene, which encodes the thrombopoietin (TPO) receptor. The main treatment for this genetic disorder is an allogeneic hematopoietic stem cell transplant (allo-HSCT). However, transplant-related mortality, development of acute and chronic graft-versushost disease (GvHD), and susceptibility to opportunistic infections are major barriers to transplantation. Delay in the reconstitution of T cells and imbalance in the regeneration of distinct functional CD4 and CD8 T-cell subsets mainly affect post-transplant complications. We report a case of CAMT, who developed acute GvHD but had no signs and symptoms of chronic GvHD following allo-HSCT.

Case presentation: At the age of four, she presented with petechiae and purpura. In laboratory investigations, pancytopenia without organomegaly, and cellularity less than 5% in bone marrow biopsy, were observed. A primary diagnosis of idiopathic aplastic anemia was made, and she was treated with prednisolone, cyclosporine, and anti-thymocyte globulin (ATG), which did not respond. Genetic analysis revealed the mutation c.1481T>G (p. L494W) in exon 10 of the c-Mpl gene, and the diagnosis of CAMT was confirmed. The patient underwent allo-HSCT from a healthy sibling donor. Alloimmunization reactions and immune disorders were present due to long-term treatment with immunosuppressive medications and repeated blood and platelet transfusions. Hence, the regeneration of T-lymphocytes after allo-HSCT was evaluated.

Conclusion: Successful treatment of acute GvHD prevented advancing the condition to chronic GvHD, and this was accompanied by delayed T-cell reconstitution through an increase in Treg:Tcons ratio.

Objective: The lung is one of the target organs of diabetes. This study aimed to probe the protective mechanism of Jiangtang Tongmai Prescription (JTTMP) against diabetic lung injury.

Methods: JTTMP-containing serum was collected, and a high glucose and high-fat diabetic cell model was established. The cells were treated with a drug-containing serum or a CAV1-associated vector. Transfection efficiency was measured by qRT-PCR and western blot, the cell proliferative capacity was tested by CCK-8 assay, and the expression of autophagosome marker LC3B was measured by immunophluorescence assay. Expression levels of the autophagy markers LC3B, p62, and Beclin-1, and the expression levels of the fibrosis markers α-SMA, FN-1, and TGF-β1 were determined by western blot, and the levels of inflammatory factors TNF-α and IL-1β in the supernatants were assessed by ELISA.

Results: In high glucose and high fat-induced MRC-5 cells, JTTMP-containing serum impeded the abnormal cell proliferation and the expression levels of autophagy markers, fibrosis markers, as well as inflammatory factors. CAV1 expression was decreased in MRC-5 cells treated with JTTMP-containing serum. In MRC-5 cells upon transfection with the CAV1 overexpression vector and treatment with JTTMP-containing serum, increased cell proliferation, increased LC3B, p62, Beclin-1, α-SMA, FN-1, and TGF-β1, TNF-α, and IL-1β levels were found compared with cells treated with JTTMP-containing serum alone.

Conclusion: This study suggests that JTTMP suppresses CAV1 expression to attenuate diabetic lung injury by reducing abnormal proliferation and autophagy, and reducing levels of fibrosis and inflammation.

Cancer-associated fibroblasts (CAFs) as a major component of cancer stroma contribute to diverse procedures of most solid tumors and might be a targeted cancer therapy approach. Their specified features, related signaling pathways, distinct biomarkers, and sub-populations need to be deciphered. There is a need for CAF extraction or induction for in vitro investigations. Some miRNAs could activate CAF-like phenotype and they also interfere in CAF-mediated drug resistance, aggressiveness, and metastatic behaviors of several cancer cell types. Due to the complex relevance of miRNA and CAFs, these non-coding oligonucleotides may serve as attractive scope for anti-cancer targeted therapies, but the lack of an efficient delivery system is still a major hurdle. Here, we have summarized the investigated information on CAF features, isolation, and induction procedures, and highlighted the miRNA-CAF communications, providing special insight into nano-delivery systems.

Background: Diabetic cardiomyopathy (DCM) is the leading cause of diabetic death as the final occurrence of heart failure and arrhythmia. Traditional Chinese medicine is usually used to treat various diseases including diabetes.

Objective: This study sought to investigate the effects of Traditional Chinese medicine supplementing Qi and activating blood circulation (SAC) in DCM.

Methods: After the construction of the DCM model by streptozotocin (STZ) injection and high glucose/fat diet feeding, rats were administered intragastrically with SAC. Then, cardiac systolic/diastolic function was evaluated by detecting left ventricular systolic pressure (LVSP), maximal rate of left ventricular pressure rise (+LVdp/dtmax), and fall (-LVdp/dtmax), heart rate (HR), left ventricular ejection fraction (EF), LV fractional shortening (FS) and left ventricular end-diastolic pressure (LVEDP). Masson’s and TUNEL staining were used to assess fibrosis and cardiomyocyte apoptosis.

Results: DCM rats exhibited impaired cardiac systolic/diastolic function manifested by decreasing LVSP, + LVdp/dtmax, -LVdp/dtmax, HR, EF and FS, and increasing LVEDP. Intriguingly, traditional Chinese medicine SAC alleviated the above-mentioned symptoms, indicating a potential role in improving cardiac function. Masson’s staining substantiated that SAC antagonized the increased collagen deposition and interstitial fibrosis area and the elevations in protein expression of fibrosis-related collagen I and fibronectin in heart tissues of DCM rats. Furthermore, TUNEL staining confirmed that traditional Chinese medicine SAC also attenuated cardiomyocyte apoptosis in DCM rats. Mechanically, DCM rats showed the aberrant activation of the TGF-β/Smad signaling, which was inhibited after SAC.

Conclusion: SAC may exert cardiac protective efficacy in DCM rats via the TGF-β/Smad signaling, indicating a new promising therapeutic approach for DCM.

It is well known that skin lesions are among the most common complications of chronic kidney disease (CKD), which significantly impact the patient's quality of life. Research has demonstrated that gut and skin lesions are closely interconnected and affect each other. This interaction is referred to as the "gut-skin axis" and the intestinal microbiota plays a critical role in this interaction. Changes in gut microbiota composition and function are associated with the development of skin diseases, which are part of the "gut-skin axis". Presently, preliminary results have been demonstrated in basic and clinical research on CKD skin lesions. With further research, the "gut-skin axis" theory can provide new ideas for treating CKD skin lesions and may become a potential treatment target.

Introduction: Qin medicines are medicinal plants growing in habitat around the peak of Qinling Mountain. Their unique curative effects on bone metabolic diseases and pain diseases have been favoured by the local people in clinical trials for thousands of years. Libanotis buchtormensis (Fisch.) DC. (LBD), is one of the popular Qin herbs, which has been widely used for the treatment of various diseases, such as osteoporosis, rheumatic, and cardiovascular diseases. However, due to the multiple compounds in LBD, the underlying molecular mechanisms of LBD remain unclear.

Objective: This study aimed to systemically investigate the underlying mechanisms of LBD against bone diseases.

Methods: In this study, a systems pharmacology platform included the potential active compound screening, target fishing, and network pharmacological analysis was employed to decipher the action mechanisms of LBD.

Results: As a result, 12 potential active compounds and 108 targets were obtained. Furthermore, compound-target network and target-pathway network analysis showed that multi-components interacted with multi-targets and multi-pathways, i.e., MARK signalling pathway, mTORC1 signalling pathway, etc., involved in the regulation of the immune system and circulatory system. These results suggested the mechanisms of the therapeutic effects of LBD on various diseases through most compounds targeted by multiple targets.

Conclusion: In conclusion, we successfully predicted the LBD bioactive compounds and potential targets, implying that LBD could be applied as a novel therapeutic herb in osteoporosis, rheumatic, and cardiovascular diseases. This work provides insight into the therapeutic mechanisms of LBD for treating various diseases.