Endocrine, metabolic & immune disorders drug targets最新文献

Introduction: The protozoan Toxoplasma (T.) gondii is responsible for toxoplasmosis, and this parasitosis represents a high risk in solid organ transplant procedures. In heart transplant patients, T. gondii infection is usually fatal since immunosuppressive drug therapy is administered to recipients.

Case presentation: A 62-year-old woman with severe biventricular dysfunction and seronegative for T. gondii underwent a cardiac transplantation from a donor seropositive for anti-T. gondii IgG antibody. The recipient exhibited post-transplant complications, including acute renal failure and difficulty in weaning from mechanical ventilation, ultimately requiring tracheotomy. The recipient underwent immunosuppressive pharmacological prophylaxis to prevent organ rejection. From a virological point of view, the recipient was monitored, and analyses of blood and serum revealed the presence of T. gondii DNA. In addition, other viral and bacterial infections were observed. Afterward, molecular and anatomopathological investigations on cardiac biopsies were performed, and neither test revealed the presence of T. gondii DNA.

Conclusion: On the one hand,prompt infection management and continuous monitoring are crucial to control viral and bacterial loads and, on the other hand, to optimise antimicrobial treatment, thus ensuring the gradual clinical stabilisation of the patient. Finally, it is important to highlight the need to review diagnostic screening protocols for organ donors to detect potential reactivation of microorganisms, viruses, and parasites that could pose a fatal risk to recipients.

Introduction: Obesity-associated inflammation promotes metabolic dysregulation and insulin resistance. Colchicine, a potent microtubule inhibitor, suppresses NLRP3 inflammasome activity and acts proximally to inhibit the inflammatory pathway. The primary objective was to evaluate the impact of intraperitoneal (IP) colchicine administration on inflammation and metabolic parameters in mice with high-fat diet-induced obesity.

Methods: C57BL/6 mice consumed a 45% fat diet from age 8 weeks to 16 weeks to induce obesity and inflammation. From weeks 12-16, 39 male and 29 female mice were randomized 1:1 to IP vehicle or IP colchicine 0.2 mg/kg/d. Glucose and insulin tolerance tests were performed, and CRP was measured to evaluate systemic inflammation. NLRP3 and Caspase-1 expression were assessed to evaluate hepatic inflammation.

Results: Body weight was lower for both male and female mice administered colchicine versus placebo (p<0.001). Serum CRP decreased in colchicine vs placebo in both male and female mice (p's<0.05). However, there was no evidence to support a colchicine-induced change in hepatic NLRP3 and Caspase-1 expression. Despite attenuating weight gain, colchicine worsened whole-body insulin sensitivity during a post-treatment insulin tolerance test compared to placebo in male mice (p < 0.01).

Discussion: In mice with high-fat diet obesity, IP colchicine 0.2 mg/kg for 4 weeks significantly suppressed inflammation but had no significant effect on markers of hepatic inflammasome activity. Colchicine treatment also induced considerable weight loss and worsened whole-body insulin sensitivity in male mice.

Conclusion: Although this dose has been used in prior short-term mouse studies to suppress inflammation, chronic administration of 0.2 mg/kg intraperitoneal colchicine appears not suitable for metabolic studies.

Introduction: In recent years, the increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) poses a serious threat to clinical anti-infection therapy. This study aims to identify risk factors for CRE infection among intensive care unit (ICU) patients.

Methodology: An unmatched case-control study based on a hospital was performed. Data on the general condition of patients, disease scores, invasive procedures, and the use of antibiotics before infection were collected. Univariate and multivariate Logistic regression were performed to analyze the risk factors for CRE infection.

Results: The univariate analysis results indicated that higher APACHE-II scores, tracheal intubation, urinary catheterization, gastric tube insertion, prior use of antibiotics, use of three or more types of antibiotics, and the use of carbapenems, broad-spectrum penicillins, antifungals, and aminoglycosides were potential risk factors for CRE infection in ICU patients. In contrast, a higher GCS score appeared to be a potential protective factor against CRE infection in ICU patients. Multivariate Logistic regression analysis showed that higher APACHE-II score (OR=2.425, 95% CI:1.713~3.946), tracheal intubation (OR=3.459, 95% CI:2.617~7.148), and the use of antibiotics before infection (OR=2.704, 95% CI: 2.013~5.358) were the risk factors of CRE infection in ICU patients; higher GCS score (OR=0.459, 95% CI: 0.349~0.725) was the protective factors of CRE infection in ICU patients.

Conclusion: Multiple risk factors for CRE infections in ICU patients are closely related to patients' clinical conditions and treatment regimens. Clinically, it is essential to regularly screen ICU patients with high-risk factors for CRE infections, enhance antimicrobial stewardship, perform pathogen cultures and identification, and minimize invasive procedures. These measures are critical for preventing and reducing CRE infections.

Introduction: Urethral stricture is a common urological disease characterized by a narrowing of the urethra leading to functional changes that reduce or completely block urine flow from the kidney to the bladder. This condition significantly affects the patient's quality of life and can lead to serious complications, such as urethral dilatation and hydronephrosis, which may result in irreversible kidney failure if left untreated.

Methods: This was an observational cross-sectional study conducted on 35 patients, treated for urethral stricture at the Department of Uro-nephrology Surgery, Ninh Thuan Province General Hospital, from January to October 2023.

Results: All enrolled patients underwent urethral stricture endoscopic incision using holmium laser, and were followed up at 1 and 3 months postoperatively. The difference in the degree of hydronephrosis on CT scans before and after surgery at 3 months was statistically significant (p < 0.01).

Discussion: To report the safety and efficacy outcomes of holmium laser urethrotomy for the treatment of urethral stricture, patients underwent internal urethrotomy with holmium laser energy, with an average age of 47.7 ± 15.8 years (range: 15-72 years). Thirty patients (85.7%) underwent urological surgery, 3 (8.6%) underwent obstetric and gynecological surgery, and 2 (5.7%) had unknown etiologic causes.

Conclusion: The use of the holmium laser for the management of urethral strictures has been found to be safe and effective, ensuring shorter operating times, a lower recurrence rate, and fewer serious postoperative complications.

Introduction: Diabetic microvascular disease (DMiVD) involves dysregulated immune cell function, but the precise pathogenic mechanisms remain unclear.

Materials and methods: We conducted a two-sample Mendelian randomization (MR) study using comprehensive GWAS and FinnGen summary statistics, encompassing 731 immune cell phenotypes, 473 gut microbial taxa, 91 inflammatory proteins, 179 lipid types, 1,400 plasma metabolites, 20 micronutrients, and DMiVD cases. The analysis aimed to evaluate causal associations between these variables and DMiVD. We further explored potential mediating roles of gut microbiota, plasma lipidome, and metabolites using mediation analysis, with multiple sensitivity tests confirming the robustness of our findings.

Results: We identified 20 immune cell phenotypes, 33 gut microbial taxa, 31 lipid types, and 83 plasma metabolites with significant causal associations with DMiVD. Mediation analysis revealed that the risk effect of CD3+ resting Tregs on diabetic nephropathy was partly mediated by phosphatidylcholine (16:0_18:2) (10.7%). Additionally, the protective effect of CX3CR1 on monocytes against DMiVD was partly mediated by Unclassified Bacilli A (35%), Species CAG-177 sp003538135 (22.6%), and triacylglycerol (52:6) (25.5%).

Discussion: These findings advance understanding of DMiVD pathogenesis, highlighting that modulation of key metabolic pathways and immune regulatory nodes may represent promising therapeutic strategies. Further experimental studies are needed to validate these potential causal relationships.

Conclusion: Using causal inference approaches, this study identifies immune cell-mediated mechanisms underlying DMiVD, involving gut microbiota, plasma lipids, and metabolites. The results suggest potential intervention targets for mechanistic studies and therapeutic development.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, influenced by both genetic and environmental factors. Among the environmental factors, early childhood self-medication may be relevant in MS development. This study aimed to evaluate the association between MS risk and self-medication practices before the age of 15.

Methods: Under a case-control approach, 260 demographically matched healthy controls from the Azeri community and 469 MS patients completed a comprehensive questionnaire on childhood self-medication history. Regarding the kind and frequency of drug usage, statistical comparisons were made among the groups using the chi-square test.

Results: Self-medication was common in both cohorts; however, individuals with multiple sclerosis exhibited a markedly greater use of corticosteroids, analgesics, and hypnotics (p < 0.05). Conversely, healthy controls reported more frequent use of iron and calcium supplements, antihistamines, acetaminophen, antibiotics, and adult cold medications (p < 0.05). No significant differences were observed for multivitamins, vitamin D, or non-steroidal anti-inflammatory drugs (p > 0.05).

Discussion: This study suggests that unsupervised use of certain medications, such as corticosteroids and hypnotics, before age 15 may increase the risk of developing multiple sclerosis, while common supplements and over-the-counter drugs may have a protective effect. Responsible drug use in childhood should be emphasized through education and regulation.

Conclusion: Early-life use of certain medications, especially corticosteroids and hypnotics, may be linked to increased MS risk, while the use of supplements and common over-the-counter drugs might have protective associations. Educational and regulatory efforts are needed to prevent unsupervised medication use in children.

Introduction: Cancer diagnosis, which is linked to a poor prognosis, frequently triggers significant patient distress. This distress can culminate in depression and reduce quality of life (QoL), impacting patient outcomes and elevating cancer mortality rates. This study aimed to explore which nursing interventions for depression management among cancer patients have been assessed and their related outcomes for all types of cancer.

Methods: A scoping search was conducted from 2018 to 2023 across the four databases. Of the initial 549 studies identified, 34 met the inclusion criteria after eliminating duplicates and verifying titles and abstracts. The methodological quality of these studies was assessed using an evidence- based nursing approach to reach a specialized scoping review abstract database for evaluating the effects of nursing interventions.

Results: The analysis yielded two distinct categories of nursing intervention. Firstly, "Helpful Nursing Interventions in Depression Outcomes in Patients with Cancer " encompassed a spectrum of efficacious strategies, including supervised exercise programs, mindfulness training, self-management psychoeducation, perioperative management, PDCA-based nursing models, and case management interventions. Secondly, "Needless Nursing Interventions in Depression Outcomes in Patients with Cancer " spotlighted interventions that failed to yield significant improvements in depression outcomes. These include palliative care consultations, web-based education, and rehabilitation programs.

Discussion: Nursing interventions vary in effectiveness and often depend on individual patient profiles and cancer staging. While some interventions significantly improve depression scores, others yield less favourable outcomes.

Conclusion: The findings of the present scoping review can be used by nurses and researchers to understand the potential benefits of nursing interventions for cancer patients and to improve similar interventions in their own clinical practices to address challenges in patients' conditions during their cancer treatment.

Introduction: This study aimed to investigate the effects of a Chinese herbal formula on the regulation of hepatic lipid metabolism in an inbred rat model of diabetes.

Methods: ZDF (fa/fa) rats were administered the herbal formula for six weeks following a five week feed of a high-fat diet. Blood glucose was monitored weekly. An oral glucose tolerance test (OGTT) and magnetic resonance imaging (MRI) were performed before sacrifice. The profiles of lipid and glucose in serum were determined, and the transcriptomic analysis was conducted. AMPK signaling was detected by PCR, western blot, and immunohistochemistry.

Results: The herbal formula improved glucose tolerance and insulin sensitivity, reduced plasma glucose and lipid, alleviated pathological changes, and decreased hepatic lipid accumulation. Transcriptomic analysis predicted that AMPK signaling was a key pathway through which the herbal formula regulated hepatic lipid metabolism. The herbal formula upregulated the expressions of AMPKα, SIRT1, and PGC1α in the liver of ZDF rats.

Discussion: The obese ZDF (fa/fa) rat, characterized by hyperglycemia, hyperlipemia, insulin resistance, and hepatic steatosis, closely mimics human T2DM. AMPK signaling plays a significant role in hepatic lipid metabolism, especially in the process of gluconeogenesis and glycogen synthesis. The herbal formula Qi Hua Tong Tiao is derived from ancient Chinese medical books in light of the Qi transformation theory. It alleviated lipotoxicity, glucotoxicity, and regulated hepatic lipid metabolism by up-regulating AMPK signaling. This study provided experimental evidence supporting the herbal formula as a promising alternative therapy for lipid disorders in diabetes.

Conclusion: The Chinese herbal formula alleviated lipotoxicity and glucotoxicity by regulating AMPK/SIRT1 in the liver of ZDF rats.

Background: Hypercalcemia is an electrolyte imbalance with multiple etiologies, the most common being primary hyperparathyroidism (PHPT). The diagnostic workup of PHPT is relatively straightforward, as elevated serum calcium levels in the presence of elevated or inappropriately normal parathyroid hormone (PTH) immediately raise the suspicion for PHPT. However, this typical presentation can be unhinged by the presence of severe vitamin D deficiency, which may mask hypercalcemia. Furthermore, vitamin D deficiency itself can contribute to PTH increase.

Case presentation: We report the case of a 53-year-old man presenting with markedly elevated PTH levels (639 pg/ml) with only borderline-elevated serum calcium (10.8 mg/dl) and severe vitamin D deficiency (5 ng/ml). Once the vitamin D level was restored to normal range with cholecalciferol supplementation, the patient developed severe hypercalcemia (14.4 mg/dl) requiring specific management.

Conclusion: This case report offers an interesting insight into the potential for cholecalciferol replacement therapy to unmask significant hypercalcemia in PHPT patients and underscores the need for caution in such a context.

Background: Neuroinflammation is a key driver of cognitive deficits after surgical menopause, a state commonly triggered by oophorectomy for oncological purposes. This intervention is routinely performed in premenopausal patients with hormone receptor-positive (HR+) breast cancer, constitutes foundational therapy for epithelial ovarian carcinoma, and is indicated for risk reduction in carriers of hereditary mutations such as breast cancer susceptibility gene 1/2 (BRCA1/2). As highly efficient immune cells, microglia play a central role in the onset of neurodegenerative diseases. Our study explored the role of thioredoxin-1 (Trx-1) in suppressing microglial activation and its potential for ameliorating postmenopausal cognitive decline.

Methods: Female C57BL/6J mice underwent ovariectomy (OVX) to model tumor-therapeutic oophorectomy. They were intraperitoneally injected with recombinant human Trx-1 (rhTrx-1) at a dose of 200 μg/30 g or PBS once weekly for five weeks following OVX. A Y-maze active avoidance task and trace fear conditioning were used to assess cognitive function. Levels of neuroinflammation were evaluated through immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and real-time polymerase chain reaction (PCR). Trx-1 levels in the hippocampus of OVX mice were measured by western blot and immunohistochemical analysis. Furthermore, the impact of Trx-1 on microglial activation was assessed in vitro.

Results: OVX induced the production of inflammatory factors and microglial activation in the brain, resulting in cognitive deficits in mice. However, intraperitoneal injection of rhTrx-1 inhibited these effects by improving cognitive function, reducing inflammatory cytokines, and promoting microglial polarization. In vitro studies also showed that rhTrx-1 attenuated lipopolysaccharide (LPS)-stimulated microglial activation through mitogen-activated protein kinase (MAPK) pathway signaling.

Discussion and conclusion: Due to its inhibitory effect on neuroinflammation and microglial activation, Trx-1 may represent a promising therapeutic candidate for managing cancer therapy-related cognitive impairment, particularly in patients undergoing estrogen-deprivation therapies such as oophorectomy.