Endocrine, metabolic & immune disorders drug targets最新文献

In this study, we examined preexisting systemic inflammation before COVID-19 (SIC), as assessed through C-reactive protein (CRP) levels, to gain insights into the origins of acute kidney injury (AKI) in adults with comorbidities affected by COVID-19. Although aging is not categorized as a disease, it is characterized by chronic inflammation, and older individuals typically exhibit higher circulating levels of inflammatory molecules, particularly CRP, compared to younger individuals. Conversely, elevated CRP concentrations in older adults have been linked with the development of comorbidities. Simultaneously, these comorbidities contribute to the production of inflammatory molecules, including CRP. Consequently, older adults with comorbidities have higher CRP concentrations than their counterparts without comorbidities or those with fewer comorbidities. Given that CRP levels are correlated with the development and severity of AKI in non-COVID-19 patients, we hypothesized that individuals with greater SIC are more likely to develop AKI during SARS-CoV-2 infection than those with less SIC.

Introduction: Neuroendocrine tumors [NETs] exhibit a wide range of clinical presentations, including the production of various hormones. Calcitonin, a sensitive marker for medullary thyroid cancer [MTC], is nonspecific and may be elevated in extra-thyroidal NETs.

Case report: We present the case of a 64-year-old female patient who underwent total thyroidectomy due to a nodule in the isthmus, with a fine-needle aspiration biopsy indicating follicular neoplasia. Pathological examination revealed macro- and micro-nodular thyroid hyperplasia, along with a parathyroid adenoma. During postoperative follow-up, a progressive elevation of calcitonin was observed, reaching 64.2 pg/ml, while carcinoembryonic antigen levels remained normal. Since no MTC foci were found upon reviewing the thyroidectomy specimen, an investigation into the origin of the elevated calcitonin was initiated. Serum chromogranin A and specific neuronal enolase levels were within normal ranges. Tc-99m HYNIC-TOC scintigraphy yielded negative results. Additionally, an upper gastrointestinal endoscopy revealed a submucosal lesion in the second portion of the duodenum, with a biopsy confirming a grade 1 NET. The patient underwent Whipple surgery and hepatic metastasectomy. Postoperatively, a decrease in baseline serum calcitonin levels was observed. Seven years after surgery, she continues specialized monitoring with no biochemical or imaging evidence of disease.

Conclusion: Serum calcitonin contributes to the diagnosis and monitoring of anterior intestine NETs.

Lung cancer and tuberculosis (TB) are classified as the second-most life-threatening diseases globally. They both are exclusively represented as major public health risks and might exhibit similar symptoms, occasionally diagnosed simultaneously. Several epidemiological studies suggest that TB is a significant risk factor for the progression of lung cancer. The staggering mortality rates of pulmonary disorders are intrinsically connected to lung cancer and TB. Numerous factors play a pivotal role in the development of TB and may promote lung carcinogenesis, particularly among the geriatric population. Understanding the intricacies involved in the association between lung carcinogenesis and TB has become a crucial demand of current research. Consequently, this study aims to comprehensively review current knowledge on the relationship between tuberculosis-related inflammation and the emergence of lung carcinoma, highlighting the impact of persistent inflammation on lung tissue, immune modulation, fibrosis, aspects of reactive oxygen species, and an altered microenvironment that are linked to the progression of tuberculosis and subsequently trigger lung carcinoma.

Androgen (AR) signaling is the main signaling for the development of the prostate and its normal functioning. AR is highly specific for testosterone and dihydrotestosterone, significantly contributing to prostate development, physiology, and cancer. All these receptors have emerged as crucial therapeutic targets for PCa. In the year 1966, the Noble prize was awarded to Huggins and Hodge for their groundbreaking discovery of AR. As it is a pioneer transcription factor, it belongs to the steroid hormone receptor family and consists of domains, including DNA binding domain (DBD), hormone response elements (HRE), C-terminal ligand binding domain (LBD), and N-terminal regulatory domains. Structural variations in AR, such as AR gene amplification, LBD mutations, alternative splicing of exons, hypermethylation of AR, and co- regulators, are major contributors to PCa. It's signaling is crucial for the development and functioning of the prostate gland, with the AR being the key player. The specificity of AR for testosterone and dihydrotestosterone is important in prostate physiology. However, when it is dysregulated, AR contributes significantly to PCa. However, the structural variations in AR, such as gene amplification, mutations, alternative splicing, and epigenetic modifications, drive the PCa progression. Therefore, understanding AR function and dysregulation is essential for developing effective therapeutic strategies. Thus, the aim of this review was to examine how AR was initially pivotal for prostate development and how it turned out to show both positive and detrimental implications for the prostate.

Background: Children born Small for Gestational Age (SGA) without early catch-up growth may show impaired growth rate, adult height, and metabolic profile [1]. Growth Hormone (GH) is recommended for their treatment, and it has been shown to have positive effects on growth and metabolic profile and good tolerability [2].

Objective: The study aimed to evaluate the auxological and metabolic effects and safety of GH treatment in SGA children.

Methods: 34 SGA children (15 F, 19 M; mean age: 8.72 ± 2.48 yrs) treated with GH (starting dosage: 32.24 ± 2.88 mcg/kg/die) were evaluated every six months for 24 months with growth and metabolic parameters.

Results: After two years, SGA children showed a significant improvement in height, weight, and growth rate, already evident after six months (p < 0.001), with a constant, significant improvement in height throughout the treatment (p ≤ 0.03 T0 vs. T12, T12 vs. T24). Conversely, although significantly higher than baseline at each visit (p < 0.001), the growth rate significantly decreased from 6 to 18 months (p ≤ 0.015 T6 vs. T12, T12 vs. T18). During the follow-up, an increase in glycemia (p ≤ 0.042 vs. T12, T18) and urycemia (p ≤ 0.01 vs. T12, T18, and T24) and a decrease in AST (p ≤ 0.021 vs. T12, T18, and T24) and LDL cholesterol (p = 0.03 vs. T24) were observed. Overall, treatment was found to be well tolerated, with poor compliance being the most frequent adverse event (11.8%) and no reported hyperglycemia.

Conclusion: In conclusion, GH can be considered an effective, safe treatment in SGA children, improving height and growth rate, although proper metabolic follow-up is required.

Background: Turner Syndrome (TS) is a rare condition in females, characterized by complete or partial loss of one X chromosome, often in mosaic karyotypes. It is associated with a wide spectrum of health problems across the age span, which requires particular attention during the transition from childhood to adult age.

Objective: The aim of this study was to assess in a consecutive sample of TS patients the clinical, biochemical, and instrumental changes during the first period after the transition from paediatric to adult care.

Methods: Sixteen patients with TS were enrolled: 9 with the karyotype 45, X0 and 7 with a mosaic karyotype. Patients' clinical information was obtained from the management software of the Hospital of Padua.

Results: The median age for transition was 18 years. All patients received an appointment in adult clinics after the last visit with the paediatrician, however, 9 patients dropped out of followup by delaying the appointment by 1-2 years. After an average follow-up of 54±36.7 months, all patients presented a significant reduction in the values of insulinemia, HOMA index and HbA1c. Lumbar and proximal femur Z-score values improved, and the prevalence of overweight was reduced among patients on sex hormone replacement therapy for at least four years.

Conclusions: This study confirms the necessity of a structured plan from paediatric to adult care for TS patients to avoid the risk of dropping out of the transition and future follow-up. A periodic monitoring protocol may guarantee an early detection and an effective correction of health complications associated with TS.

Objective: The study aimed to investigate the efficacy and safety of semaglutide in weight loss in non-diabetic people.

Methods: In this study, 84 non-diabetic people who used semaglutide to lose weight in the outpatient department of our hospital from January 1, 2022, to June 30, 2022, were enrolled and compared for changes in body weight, waist circumference, Body Mass Index (BMI), fasting blood glucose, blood pressure, pulse, and body composition (body fat ratio, visceral fat area, and skeletal muscle) before treatment and 12 weeks after the treatment to analyze the weight loss efficacy and safety.

Results: After administering semaglutide 0.25 mg, 0.5 mg, 0.75 mg, or 1 mg subcutaneously once a week for 12 weeks, 84 participants in this study obtained an average weight loss of 5.91 ± 3.37 kg, equivalent to 6.15 ± 4.28% of baseline body weight, and there was also a significant reduction in visceral fat area and a slight reduction in blood pressure. The most common adverse reactions included gastrointestinal reactions (nausea, vomiting, and diarrhea), which were mild and subsided within 1-2 days. No severe adverse reaction, such as hypoglycemia and hypotension, was observed.

Conclusion: Low-dose semaglutide has been found to be effective and safe for short-term weight loss in non-diabetic people.

Background and aims: Inflammatory Bowel Disease (IBD) is a refractory disease with repeated attacks, and there is no accurate treatment target at present. Dipyridamole, a phosphodiesterase (PDE) inhibitor, has been proven to be an effective treatment for IBD in a pilot study. This study explored the therapeutic target of IBD and the pharmacological mechanism of dipyridamole for the treatment of IBD.

Materials and methods: The candidate targets of dipyridamole were obtained by searching the pharmMapper online server and Swiss Target Prediction Database. The IBD-related targets were selected from four GEO chips and three databases, including Genecards, DisGeNET, and TTD database. A protein-protein interaction (PPI) network was constructed, and the core targets were identified according to the topological structure. KEGG and GO enrichment analysis and BioGPS location were performed. Finally, molecular docking was used to verify dipyridamole and the hub targets.

Results: We obtained 112 up-regulated genes and 157 down-regulated genes, as well as 105 composite targets of Dipyridamole-IBD. Through the PPI network analysis, we obtained the 7 hub targets, including SRC, EGFR, MAPK1, MAPK14, MAPK8, PTPN11, and LCK. The BioGPS showed that these genes were highly expressed in the immune system, digestive system, and endocrine system. In addition, the 7 hub targets had good intermolecular interactions with dipyridamole. The therapeutic effect of dipyridamole on IBD may involve immune system activation and regulation of inflammatory reactions involved in the regulation of extracellular matrix, perinuclear region of cytoplasm, protein kinase binding, and positive regulation of programmed cell death through cancer pathway (proteoglycans in cancer), lipid metabolism, Ras signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway, Th17 cell differentiation, and other cellular and innate immune signaling pathways.

Conclusion: This study predicted the therapeutic target of IBD and the molecular mechanism of dipyridamole in treating IBD, providing a new direction for the treatment of IBD and a theoretical basis for further research.

The COVID-19 pandemic impacted all areas of daily life, including medical care. Unfortunately, to date, no specific treatments have been found for the cure of this disease, and therefore, it is advisable to implement all possible strategies to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. There is sufficient evidence to demonstrate that immune response can be weakened by inadequate nutrition. Nutrition management and treatment are very important to enhance the immune response of an infected person against RNA viral infection. A complete nutritional assessment should include anthropometric, dietary, and laboratorial assessment, as well as a multidisciplinary discussion about the patient's clinical condition. In this way, it is possible to establish an individualized nutritional approach to contribute to improving clinical and nutritional prognoses. From this point of view, diet, through intake of vitamins and trace elements and maintaining adequate functioning of the intestinal barrier, can reduce the severity of the COVID-19 infection. In this study, we provide an overview of the effects of diet on COVID-19 infection in non-cancer patients. This notion needs to be further evaluated, and thus, identification, characterization, and targeting of the right nutrition principles related to the management of patients with COVID-19 are likely to improve outcomes and may prevent the infection or lead to a cure.

Background: Calcitonin (CT) is a sensitive serum marker of medullary thyroid carcinoma usually detected via immunoassays; however, its levels are easily disturbed by several endogenous factors.

Objective: The study aimed to discuss a case of suspected interference resulting in aberrant CT values and review previous reports of CT interference.

Methods: A female patient visited our clinic with a physical ultrasound examination showing a slightly enlarged thyroid gland with small nodules. She had elevated CT levels, inconsistent with the clinical presentation and other findings. We evaluated the results by retesting using the same platform, platform validation, multiplex dilution, Polyethylene Glycol (PEG) precipitation, heterophilic blocking tubes, and RET gene analysis.

Results: Retesting CT using the same platform confirmed the high value obtained. However, serial dilution of the sample produced nonlinear results, suggesting some interference. While PEG precipitation did not significantly reduce the CT level, incubating the sample in HBTs normalized the CT value, indicating interference from heterophilic antibodies. Gene sequencing revealed no RET mutations.

Conclusion: In cases where elevated CT levels are inconsistent with clinical presentations and other findings, the laboratory technicians should communicate with clinicians, analyze the reasons for the inconsistent results, and use different methods to verify the results. Accurate testing provides realistic and reliable data for doctors and patients and helps to avoid unnecessary procedures.