Endocrine, metabolic & immune disorders drug targets最新文献

Diabetes mellitus (DM) is the most common metabolic disorder that occurs due to the loss, or impaired function of insulin-secreting pancreatic beta cells, which are of two types - type 1 (T1D) and type 2 (T2D). To cure DM, the replacement of the destroyed pancreatic beta cells of islet of Langerhans is the most widely practiced treatment. For this, isolating neuronal stem cells and cultivating them as a source of renewable beta cells is a significant breakthrough in medicine. The functions, growth, and gene expression of insulin-producing pancreatic beta cells and neurons are very similar in many ways. A diabetic patient's neural stem cells (obtained from the hippocampus and olfactory bulb) can be used as a replacement source of beta cells for regenerative therapy to treat diabetes. The same protocol used to create functional neurons from progenitor cells can be used to create beta cells. Recent research suggests that replacing lost pancreatic beta cells with autologous transplantation of insulin-producing neural progenitor cells may be a perfect therapeutic strategy for diabetes, allowing for a safe and normal restoration of function and a reduction in potential risks and a long-term cure.

Background: The aim of this study is to analyze the effects of colostrum application on the establishment of normal flora in the intestinal tracts and oral cavities of extremely low birth weight infants (ELBWI).

Methods: A prospective cohort study design was adopted following the STROBE guidelines (Supplementary File 1). Colostrum was administered immediately after obtaining maternal breast milk using a special sterile cotton swab. There were no specific treatments for infants who did not receive colostrum. This experiment was completed on day 5 post-birth and the patients were divided into the colostrum and control groups, corresponding to whether or not colostrum was administered. Throat swabs and stool samples were collected on days 1 and 5 post-birth.

Results: Using the conventional bacteria cultivation technique, the detection rate of bacteria in 98 cases of meconium at birth was 15.31%. On day 5, the detection rates of Staphylococcus in the colostrum and control groups were 36.54% and 34.78%, with no significant difference between them (P = 0.856), and that of Enterococcus was 26.92% and 13.04%, respectively, with no statistically significant difference (P = 0.089). Likewise, at birth, the detection rate of bacteria in 98 cases of throat swabs was 27.55%. On day 5, the detection rate of Streptococcus in the colostrum and control groups was 78.85% and 50.00%, respectively, recording a statistically significant difference this time (P = 0.003).

Conclusion: Colostrum application had limited effects on intestinal flora colonization but contributes to physiological oral flora colonization.

Obesity is a chronic lifestyle issue with devastating results. Behavioral changes are one of the initial lines of management strategies for obesity, but they are not very efficient management strategies. Many people also use surgical intervention to maintain a healthy weight, now considered to be the most common and effective obesity management. Chemically synthesized medicines fill the gap between lifestyle interventions and minimally invasive surgical management of obesity. The most common issue associated with monotherapy without side effects is its moderate effectiveness and higher dose requirement. Combination therapy is already used for many serious and complicated disease treatments and management and has shown efficacy as well. Generally, we use two or more medicines with different mechanisms of action for a better effect. The commonly used combination therapy for obesity management includes low-dose phentermine and prolonged and slow-releasing mechanism topiramate; naltrexone, and bupropion. Phentermine with inhibitors of Na-glucose cotransporter-2 or glucagon-like peptide-1 (GLP-1) agonists with gastric hormone or Na-glucose cotransporter-2 are two more viable combo therapy. This combination strategy aims to achieve success in bariatric surgery and the scientific community is working in this direction.

Background: Resistance to TSH is defined as reduced sensitivity to normal, biologicallyactive TSH, and abnormally high levels of TSH are needed to achieve normal levels of thyroid hormones.

Case presentation: A 15-year-old female patient, having been treated since childhood with levothyroxine for hyperthyrotropinemia was referred to our institution complaining of tachycardia after the levothyroxine therapy had been increased. Thyroid ultrasound features were normal, and thyroid antibodies were negative. The therapy was gradually tapered in light of the symptoms, although subclinical hypothyroidism was evident at thyroid function tests. First-degree relatives were tested for thyroid function, and the father was also found to have a previously-unknown subclinical hypothyroidism. The patient underwent genetic testing for TSH receptor (TSHR) gene mutations, which revealed a gene variant hitherto not described: p.C598R (c.1792T>C). The father was also tested and was found to carry the same mutation, while other first-degree relatives were wild-type for the TSHR gene. An in-silico analysis was performed, which revealed a loss-of-function phenotype corresponding to the described variant, suggesting a novel loss-of-function TSH receptor gene mutation.

Conclusion: In this case report, we present a novel loss-of-function gene mutation in the TSH receptor gene associated with a TSH resistance phenotype.

Introduction: Amyloid goiter is a rare disease characterized by amyloid deposits that cause sudden growth in the thyroid gland.

Case presentation: Here we present a case of a 26-year-old woman with euthyroid amyloid goiter who presented with subacute granulomatous thyroiditis clinic. Amyloid goiter was detected as a result of core biopsy from the thyroid parenchyma of the patient with sudden thyroid enlargement. Surgery was not applied to the patient who had no pressure symptoms or signs. In systemic amyloidosis secondary to Familial Mediterranean fever, heart and kidney involvement, as well as the thyroid gland, were detected.

Conclusion: Amyloid accumulation should be considered in addition to anaplastic thyroid cancer and lymphoma in patients with sudden thyroid enlargement. It should not be overlooked that amyloid goiter may mimic subacute thyroiditis clinic. Systemic amyloidosis should be considered in patients with amyloid goiter, and an examination should be made to assess the presence of amyloid accumulations in other organs.

Latex allergy is a hypersensitivity response to natural rubber latex (NRL) proteins or rubber chemicals used in the manufacture of latex products. An accurate diagnosis is the first step in the effective management of individuals with latex allergy, especially in high-risk groups, such as healthcare workers and those affected by spina bifida. Diagnosis is based on the clinical history and an accurate allergological evaluation. In the case of type I IgE-mediated hypersensitivity reactions, which can manifest urticaria, angioedema, rhinoconjunctivitis, asthma and anaphylaxis after latex exposure, skin prick tests or latex-specific IgE (sIgE) antibody detection using serological assays can be performed to confirm sensitization. Instead, in the case of contact dermatitis, a patch test can be applied to confirm the presence of a type IV T cell-mediated hypersensitivity reaction to rubber accelerators or additives. Basophils activation tests or challenge tests may be performed if there's an incongruity between the clinical history and the results of in vivo and in vitro tests. The aim of this review is to analyze the current state of the art of diagnostic techniques for latex allergy and algorithms employed in clinical practice and possible future developments in this field.

Insulin resistance, i.e., decreased biological response to insulin, is a risk factor for many diseases, such as obesity, type 2 diabetes (T2DM), cardiovascular disease, polycystic ovary syndrome, some forms of cancer and neurodegenerative diseases. One of its main causes is chronic low-grade inflammation, mediated by the proinflammatory pathways, such as the c-Jun N-terminal kinase (JNK) pathway and the nuclear factor kappa B (NFκB) pathway. Interleukin (IL)-38 (IL-38) is a newly discovered cytokine that belongs to the IL-1 family. There are three hypothetical pathways through which IL-38 may bind to the specific receptors and inhibit their proinflammatory activity. Those pathways are associated with IL-36 receptor (IL-36R), IL-1 receptor accessory protein-like 1 (IL1RAPL1) and IL-1 receptor 1 (IL1R1). There are studies linking IL-38 to improve insulin sensitivity through the difference in serum IL-38 in patients with insulin resistance or the correlation of IL-38 concentrations with insulin resistance indexes. However, many questions still remain regarding the biological activity of IL-38 itself and its role in the pathogenesis of insulin resistance. The goal of this study is to showcase IL-38, its biological activity, hypothesized signaling pathways, connection with insulin resistance and future perspectives of research on IL-38. We present that IL-38 associated signaling can be a potential target for the treatment of insulin resistance and associated diseases.

Aims: Papillary thyroid cancer (PTC) is one of the subtypes of thyroid cancer with increasing incidence worldwide, but the molecular mechanism is still unclear.

Background: Papillary thyroid cancer (PTC) is one of the subtypes of thyroid cancer with increasing incidence worldwide, but the molecular mechanism is still unclear. Studies have indicated that nectin cell adhesion molecule 4 (NECTIN4) was an oncogene and played an important role in the development and progression of PTC. Meanwhile, specificity protein 1 (SP1) expresses many important oncogenes and tumor suppressor genes. However, the relationship between NECTIN4 and SP1 in regulating PTC growth is unclear.

Objective: In the present study, reverse transcription PCR was utilized to detect the mRNA expression of NECTIN4 and SP1 in thyroid cancer cell lines and normal thyroid cell lines. Chromatin immunoprecipitation assays and luciferase reporter assays were used to study whether SP1 could bind to the promoter region of NECTIN4 and activate its transcription. The biological functions of SP1 correlated with NECTIN4 were also performed in TPC-1 and KTC1 cell lines.

Methods: The study revealed that the mRNA expression level of SP1 and NECTIN-4 showed a positive correlation and were upregulated in PTC cell lines. Moreover, the results of ChIP and luciferase reporter assays showed that SP1 could bind to the NECTIN4 promoter regions and activate the transcriptional level of NECTIN4.

Results: The experiments in vitro showed that SP1 could promote cell proliferation, colony formation, migration, and invasion by regulating NECTIN4 in PTC cells.

Conclusion: In conclusion, our study, for the first time, demonstrated that SP1 could control the transcriptional regulation of NECTIN4 and accelerate the growth of PTC, which may provide a new potential therapeutic target for PTC patients.