Development Of Disease Research Articles

Contribution of gut microbiota to the development of Crohn's disease: Insights gained from fecal microbiota transplantation studies in mice

We would like to present some new thoughts on the publication in the journal published in August 2024 in World Journal of Gastroenterology . We specifically focused on the alterations in the intestinal tract, mesenteric adipose tissue (MAT), and systemic inflammatory changes in mice following fecal flora transplantation into a mouse model of Crohn's disease (CD). Accumulating evidence suggests that the occurrence of CD is influenced by environmental factors, host immune status, genetic susceptibility, and flora imbalance. One microbiota-based intervention, fecal microbiota transplantation, has emerged as a potential treatment option for CD. The MAT is considered a "second barrier" around the inflamed intestine. The interaction between gut microbes and inflammatory changes in MAT has attracted considerable interest. In the study under discussion, the authors transplanted fetal fecal microorganisms from patients with CD and clinically healthy donors, respectively, into 2,4,6-trinitrobenzene sulfonic acid-induced CD mice. The research explored the complex interplay between MAT, creeping fat, inflammation, and intestinal flora in CD by evaluating intestinal and mesenteric lesions, along with the systemic inflammatory state in the mice. This article provides several important insights. First, the transplantation of intestinal flora holds significant potential as a therapeutic strategy for CD, offering hope for patients with CD. Second, it presents a novel approach to the diagnosis and treatment of CD: The inflammatory response in CD could potentially be assessed through pathological or imaging changes in the MAT, and CD could be treated by targeting the inflammation of the MAT.

Psoriasis Risk With Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are recognized as revolutionary cancer therapies but have raised concerns about immune-related adverse events, including the development of autoimmune diseases. To evaluate the psoriasis risk associated with the use of ICIs in patients with cancer. This nationwide cohort study with a target trial emulation design used data from the Taiwan National Health Insurance database and the Taiwan Cancer Registry. The participants included were patients who received antineoplastic medications for cancer at stages III and IV between January 1, 2019, and June 30, 2021. Data were analyzed from May 2023 to July 2024. Patients treated with ICIs were classified as ICI users, while those who received chemotherapy or targeted therapies were categorized as non-ICI users. The primary outcome was the incidence of psoriasis during the follow-up period. Stabilized inverse probability of treatment weighting (IPTW) was used to mitigate potential confounders. Cox and Fine-Gray hazard models were used to calculate hazard ratios (HRs) for psoriasis risk between groups. Of 135 230 patients who received antineoplastic medications (mean [SD] age, 62.94 [13.01] years; 45.1% female), 3188 patients were eligible for the ICI user group, while 132 042 patients were eligible for the non-ICI user group. ICI users experienced a higher incidence of psoriasis at 5.76 cases per 1000 person-years, compared to 1.44 cases in the non-ICI group. After adjusting for demographics and comorbidities, ICI users were found to have a 2-fold increase in the risk of developing psoriasis (IPTW-adjusted HR, 3.31; IPTW-adjusted subdistribution HR, 2.43). Both as-started design and on-treatment design showed consistent findings, and the results were consistent and robust across all follow-up intervals and all sensitivity analyses. In this cohort study, patients with cancer treated with ICIs faced an increased risk of psoriasis. Medical professionals should be aware of the potential adverse effects of immunotherapy to ensure optimal cancer care.

Investigation of homocysteine level after bariatric metabolic surgery, effect on vitamin B12 and folate levels.

Obesity is a serious health problem with increasing incidence. worldwide and remains one of the most important causes of preventable deaths. We aimed to examine the relationship between Vitamin B12 and Folic acid, which have an important role for human life, and homocysteine is widely recognized for its association with the development of cardiovascular disease, although its role as an independent risk factor remains a topic of ongoing debate. We evaluated 126 patients who underwent bariatric metabolic surgery between September 2019-September 2020. In addition to demographic characteristics of the patients, weight, Vitamin B12, folate, HbA1c, cholesterol, triglyceride, ferritin, serum iron, albumin levels at preoperative, postoperative 1st month, 6th month, 12th month follow-ups were analyzed. Patients with the desired biochemical parameters at the determined follow-up points were identified and two groups were formed as RYGB(n = 43) and SG(n = 7) patients. When biochemical parameters were analyzed between the groups, homocysteine, HbA1c, HDL Cholesterol, VLDL Cholesterol, Total Cholesterol, Triglycerides, Ferritin, Serum Iron levels showed a statistical difference (p < 0.001). Folate (p = 0.064) and albumin (p = 0.257) did not show a significant difference over time. The change in vitamin B12 (p = 0.409) over time was not significant in the SG group, whereas a significant difference was observed in the RYGB group (p < 0.001). When we established a marginal model to determine the factors affecting the change in homocysteine over time, vitamin B12 and folate values. The relationship between Vitamin B12, folate and homocysteine is important in order to better understand the complications that develop in bariatric metabolic surgery patients, to prevent possible complications and to better manage the process.

Epicardial Adipocytes in Cardiac Pathology and Healing.

Implications of epicardial adipose tissue (EAT) on the development of coronary artery disease (CAD) have garnered recent attention. Located between the myocardium and visceral pericardium, EAT possesses unique morphological and physiological contiguity to the heart. The transcriptome and secretome of EAT differ from that of other fat stores in the body. Physiologically, EAT protects the adjacent myocardium through its brown-fat-like thermogenic function and rapid fatty acid oxidation. However, EAT releases pro-inflammatory mediators acting on the myocardium and coronary vessels, thus contributing to the development and progression of cardiovascular diseases (CVD). Furthermore, EAT-derived mesenchymal stromal cells indicate promising regenerative capabilities that offer novel opportunities in cell-based cardiac regeneration. This review aims to provide a comprehensive understanding and unraveling of EAT mechanisms implicated in regulating cardiac function and regeneration under pathological conditions. A holistic understanding of the multifaceted nature of EAT is essential to the future development of pharmacological and therapeutic interventions for the management of CVD.

The Implications of Handwashing and Skin Hygiene on Infectious Disease Dynamics: The African Scenario

Infectious diseases are largely preventable, yet they continue to pose a significant threat to public health, particularly among vulnerable populations in developing countries. Basic hygiene practices, especially hand and skin hygiene, have been shown to significantly reduce the risk of the cross-transmission of infections, including those caused by multi-drug-resistant organisms. In light of the growing global concern about antimicrobial resistance, there is an urgent need to review and reinforce these practices. This study provides a general overview of the role that hand hygiene practices play in decreasing infectious diseases by conducting a comprehensive review. Multiple online databases, including Google Scholar, Scopus, and Web of Science, were searched using relevant keywords such as “hygiene practices”, “infectious diseases”, “public health”, “Africa”, and “sanitation”. After filtering the search results for relevancy, selected studies were narratively synthesized to present the latest data on hand hygiene and its impact on infectious diseases. Strengthening hand and skin hygiene, along with environmental sanitation and preventive measures, can help reduce the spread of nosocomial infections. By emphasizing the importance of these fundamental hygiene practices, particularly in regions where the burden of infectious diseases is highest, the development of antibiotic-resistant diseases can be prevented, improving patient safety, and enhancing public health outcomes. Adopting comprehensive hygiene policies, including regular handwashing, is crucial for reducing the prevalence of infectious diseases and improving health outcomes in developing countries.

Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases

Neddylation, a type of protein post-translational modification that links the ubiquitin-like protein NEDD8 to substrate proteins, can be involved in various significant cellular processes and generate multiple biological effects. Currently, the best-characterized substrates of neddylation are the Cullin protein family, which is the core subunit of the Cullin-RING E3 ubiquitin ligase complex and controls many important biological processes by promoting ubiquitination and subsequent degradation of various key regulatory proteins. The normal or abnormal process of protein neddylation in the central nervous system can lead to a series of occurrences of normal functions and the development of diseases, providing an attractive, reasonable, and effective targeted therapeutic strategy. Therefore, this study reviews the phenomenon of neddylation in the central nervous system and summarizes the corresponding substrates. Finally, we provide a detailed description of neddylation involved in CNS diseases and treatment methods that may be used to regulate neddylation for the treatment of related diseases.

Probiotic, Postbiotic, and Paraprobiotic Effects of Lactobacillus rhamnosus as a Modulator of Obesity-Associated Factors

Obesity is a pandemic currently affecting the world’s population that decreases the quality of life and promotes the development of chronic non-communicable diseases. Lactobacillus rhamnosus is recognized for multiple positive effects on obesity and overall health. In fact, such effects may occur even when the microorganisms do not remain alive (paraprobiotic effects). This raises the need to elucidate the mechanisms by which obesity-associated factors can be modulated. This narrative review explores recent findings on the effects of L. rhamnosus, particularly, its postbiotic and paraprobiotic effects, on the modulation of adiposity, weight gain, oxidative stress, inflammation, adipokines, satiety, and maintenance of intestinal integrity, with the aim of providing a better understanding of its mechanisms of action in order to contribute to streamlining its clinical and therapeutic applications. The literature shows that L. rhamnosus can modulate obesity-associated factors when analyzed in vitro and in vivo. Moreover, its postbiotic and paraprobiotic effects may be comparable to the more studied probiotic actions. Some mechanisms involve regulation of gene expression, intracellular signaling, and enteroendocrine communication, among others. We conclude that the evidence is promising, although there are still multiple knowledge gaps that require further study in order to fully utilize L. rhamnosus to improve human health.

Olfactory Development and Dysfunction - Involvement of Microglia.

Olfactory deficits are increasingly recognized in a variety of neurological, neurodevelopmental, psychiatric and viral diseases. While the pathology underlying olfactory loss is likely to differ across diseases, one shared feature may be an immune response mediated by microglia. Microglia orchestrate the brain's response to environmental insults and maintain neurodevelopmental homeostasis. Here, we explore the potential involvement of microglia in olfactory development and loss in disease. The effects of microglia-mediated immune response during development may be of special relevance to the olfactory system, which is unique in both its vulnerability to environmental insults as well as its extended period of neurogenesis and neuronal migration.

Biological plausibility and implications of obesity associated valvular heart diseases

Obesity contributes to the development and progression of cardiovascular risk factors and diseases, but so far not much attention has been given to obesity and valvular heart disease. Several observational and mendelian randomization studies have reported an association between body mass index with aortic valve stenosis, but also with secondary functional mitral regurgitation and tricuspid regurgitation in a more indirect manner. Several mechanisms can lead to the link between obesity and valvular heart diseases: left ventricular dilation, as obesity directly contributes to ischemic heart disease and ventricular remodeling, atrial myopathy as well as atrial remodeing and arrhythmias, such as atrial fibrillation, that predispose to valvular regurgitation, but also pulmonary hypertension, which could be the consequence of obesity-related inflammation, insulin resistance, and oxidative stress, valvular calcification which is often associated with adiposity and as a direct effect of increased epicardial adipose tissue and pericardial restraint. Individuals with obesity associated valvular heart disease may experience worse symptoms, quality-of-life, exercise capacity, and risk for adverse outcomes. The effect of and the mechanism for various vavular heart diseases in relation to obesity has not been investigated in depth. Recently, incretin-based drugs and sodium-glucose cotransporter-2 inhibitors have been shown to reduce adiposity, and improve HF outcomes; however, the implications of these drugs on valvular heart diseases have not been evaluated. With innovations in therapies for obesity, several questions merit discussion. Considering the prevalence of obesity and its association with valvular heart diseases, not studying these common comorbid conditions represents a significant missed opportunity.

Walnut Consumption May Contribute to Healthy Cardiovascular Endothelial Function by Maintaining Membrane Integrity

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. A healthy diet has an important role in delaying the development of many modifiable risk factors of CVD, including abdominal obesity, high blood pressure, high plasma levels of cholesterol, and glucose. The consumption of various nuts, especially walnuts, may benefit both primary and secondary prevention due to their bioactive components. This review focuses on (1) the protective role of walnut consumption on CVD at large (2) and the potential cellular and molecular mechanisms by which they have beneficial effects on vascular endothelial function. Walnuts contain many essential ingredients (such as polyunsaturated fatty acids, phenolic compounds, and vitamin E) necessary for the healthy functioning of membranes. Since membranes are involved in nearly all processes associated with life-related function, the main underlying mechanism of walnut-improved cardiovascular function is likely based on improving membrane composition and function by providing all of the substrates necessary for membranes, such as cell, mitochondria, Golgi, nucleus, and so on. In addition to endothelial cell function, all other cells and membranes are likely to benefit from walnut consumption, suggesting that incorporating walnuts into the human diet is essential, for example, during higher physical and mental demand, such as exercise, and may mitigate the risk for the development of cardiovascular diseases and compensate for the sedentary lifestyle, especially in those of an older age.

Black Garlic Supplementation and Glomerular Protection in Hyperuricemic Rats: A Study on Kidney Health Prevention

Introduction: Hyperuricemia is a significant risk factor for the development of chronic kidney disease. Excessive uric acid can deposit in the kidneys, triggering inflammatory reactions and oxidative stress, leading to structural damage in the glomeruli. Black garlic, with its antioxidant and bioactive compounds, has the potential to protect the kidneys from hyperuricemia-induced damage. Our objective is to evaluate the effect of black garlic supplementation on the histopathological features of glomeruli in a hyperuricemic rat model. Methods: This study was an analytical observational study using Biological Remnant Materials (BRM) from a previous study. The sample consisted of 30 male Sprague-Dawley rats divided into 5 groups: disease control, drug control (allopurinol), and 3 black garlic dose groups (240 mg/day, 480 mg/day, and 960 mg/day). Data were collected through histopathological examination of kidney tissue using the glomerular damage scoring method (0-3). Data analysis was performed using one-way ANOVA and post hoc LSD tests. Results: Black garlic demonstrated protective effects on the histopathological features of glomeruli in hyperuricemic rats. The 240 mg/day dose showed the most significant improvement in kidney health, reducing glomerular damage scores compared to the disease control group (p &lt; 0.05). These findings suggest that black garlic can serve as a preventive agent against kidney complications caused by hyperuricemia. Conclusion: Black garlic provides protective effects on glomerular histopathology in hyperuricemic rats, with the 240 mg/day dose being the most effective. These results suggest potential use for black garlic in preventing kidney complications in hyperuricemia.

3-Oxo-11αH-germacra-1(10) E,4Z-dien-12,6α-olide, a sesquiterpene from Artemisia sieversiana, attenuates lipopolysaccharide-induced inflammation via NF-κB/MAPK pathways and oxidative stress via ROS pathway in RAW264.7 cells.

Inflammation is a vital and normalphysiological response; however, excessive inflammation can contribute to the development of various diseases. Artemisia sieversiana, a traditional Chinese medicinal plant, contains a variety of chemical compounds. One such compound, 3-oxo-11αH-germacra-1(10)E,4Z-dien-12,6α-olide, a germacranolide sesquiterpenoid (germacranolide, GMO), has not been thoroughly investigated regarding its potential anti-inflammatory properties. In this study, the anti-inflammatory and antioxidant properties of GMO were investigated for the lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. It was demonstrated that GMO effectively suppressed the production of inflammatory mediators, decreased the phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) in RAW264.7 cells. Additionally, GMO exhibited the capacity to mitigate oxidative damage induced by LPS, as indicated by assessments of reactive oxygen species and mitochondrial membrane potential. In summary, GMO possesses significant anti-inflammatory effects by modulating the NF-κB/MAPK pathway and antioxidant effects by regulating ROS production.

Incidence, risk factors for metabolic syndrome and health systems capacity for its management amongst people living with HIV, Accra-Ghana: A study protocol.

Metabolic syndrome (MetS) refers to the clustering of three or more metabolic disorders including high blood pressure, glucose impairment, abdominal obesity, high triglycerides, and low high-density lipoproteins. MetS is increasingly being considered an epidemic among People Living With HIV (PLWH) with reports of association between HIV infection and/or antiretroviral therapy (ART) usage and development of MetS. MetS predisposes PLWH to the development of cardiovascular, kidney diseases and diabetes, decreases the quality of life, and burdens the health system. This study aims to establish the incidence, time to development and risk factors for development of MetS and it's components, and to assess the capacity of the health system to manage MetS and it's components among ART naive PLWH in Accra, Ghana. We will conduct a mixed methods study with quantitative and qualitative data collection. Our prospective cohort study would enroll adults of 18 years and above with none or less than three MetS components at baseline and follow them up at six months and one year. Demographic, lifestyle data, anthropometric, and laboratory data will be collected using an adapted WHO Steps Survey questionnaire. The WHO Service Availability and Readiness Questionnaire (SARA) will be adapted to collect information on capacity across the six WHO building blocks. Key informant interviews will be conducted with HIV coordinators at the national, regional, and facility levels. In-depth interviews will be conducted with PLWH from the cohort who develop MetS or MetS components during their follow-up. Data will be analysed using proportions, Kaplan Mier time to event analysis, fitting of Cox proportional hazard regression models for risk factors, and generation of themes from qualitative data. This study will generate data on the incidence, time to development, risk factors for MetS and MetS components development, and health systems capacity for MetS management among PLWH. Findings would inform revisions to the guidelines and policies for HIV care in Ghana, Africa, and beyond, ultimately improving MetS prevention and management among the vulnerable population of PLWH.

Noninvasive, Multimodal Inflammatory Biomarker Discovery for Systemic Inflammation (NOVA Study): Protocol for a Cross-Sectional Study.

Prolonged systemic inflammation is recognized as a major contributor to the development of various chronic inflammatory diseases. Daily measurements of inflammatory biomarkers can significantly improve disease monitoring of systemic inflammation, thus contributing to reducing the burden on patients and the health care system. There exists, however, no scalable, cost-efficient, and noninvasive biomarker for remote assessment of systemic inflammation. To this end, we propose a novel, multimodal, and noninvasive approach for measuring inflammatory biomarkers. This study aimed to evaluate the relationship between the levels of inflammatory biomarkers in serum (gold standard) and those measured noninvasively in urine, sweat, saliva, exhaled breath, stool, and core body temperature in patients with systemic inflammation. This study is a single-center, cross-sectional study and includes a total of 20 participants (10 patients with systemic inflammation and 10 control patients). Eligible participants provide serum, urine, sweat, saliva, exhaled breath, and stool samples for biomarker analyses. Core body temperature is measured using a sensor. The primary end point is the level of C-reactive protein (CRP). The secondary end points are interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α levels. The tertiary end points are fractional exhaled nitric oxide, calprotectin, and core body temperature. Samples will be collected in 2 batches, enabling preliminary analysis of the first batch (patients 1-5 from each group). The full analysis will include both batches. CRP and cytokine levels will be measured using enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay. For statistical analysis, the Shapiro-Wilk test will be used to evaluate the normality of the distribution in each variable. We will perform the 2-tailed t test or Wilcoxon rank sum test to compare the levels of inflammatory biomarkers between patients with systemic inflammations and control patients. Pearson and Spearman correlation coefficients will assess the relationship between inflammatory biomarkers from noninvasive methods and serum biomarkers. Using all-subset regression analysis, we will determine the combination of noninvasive methods yielding the highest predictive accuracy for serum CRP levels. Participants' preferences for sampling methods will be assessed through a questionnaire. The study received ethics approval from the independent research ethics committee of Canton Zurich on October 28, 2022. A total of 20 participants participated in the study measurements. Data collection started on February 22, 2023, and was completed on September 22, 2023. Participants were on average 52.8 (SD 14.4; range 24-82) years of age, and 70% (14/20) of them were women. The analysis results reporting findings are expected to be published in 2025. This study aims to evaluate the feasibility of noninvasive, multimodal assessment of inflammatory biomarkers in patients with systemic inflammation. Promising results could lead to the creation of noninvasive and potentially digital biomarkers for systemic inflammation, enabling continuous monitoring and early diagnosis of inflammatory activity in a remote setting. DERR1-10.2196/62877.

Surrogate Endpoints in APOL1-Associated Kidney Disease: Evaluation in Three Cohorts.

Surrogate endpoints for the clinical outcome of kidney failure have been accepted by the United States Food and Drug Administration. However, they have not been specifically evaluated in Apolipoprotein L1 (APOL1)-associated kidney disease. This random-effects meta-analysis included African-American participants in the Atherosclerosis Risk in Communities (ARIC) study (N=3071), the Chronic Renal Insufficiency Cohort (CRIC; N=998), and the African American Study of Kidney Disease and Hypertension (AASK; N=609). Surrogate endpoints included three-year 30% and 40% decline in glomerular filtration rate (GFR), doubling of urine protein-to-creatinine ratio (UPCR), and >3 ml/min/1.73 m2 per year decline in GFR. Clinical outcomes included kidney failure requiring kidney replacement therapy, heart failure, cardiovascular disease, and death after three years.Results: 22% in AASK, 18% in CRIC, and 13% in ARIC had the APOL1 high risk genotype. Participants with the APOL1 high-risk genotype had higher risk of all three-year GFR outcomes but not doubling of UPCR, as well as kidney failure after three years. The three-year outcomes were strongly associated with kidney failure, with weaker but statistically significant associations with the development of heart failure, cardiovascular disease, and mortality. There were no differences in associations between short-term and long-term clinical outcomes by APOL1 risk status. Individuals with the APOL1 high risk genotype were more susceptible to three-year GFR-related endpoints and long-term kidney failure than individuals with the APOL1 low-risk genotype. There was no consistent difference in short-term-clinical outcome associations by APOL1 genotype, supporting the use of surrogates in APOL1-associated kidney disease.

Encapsulated Predatory Bacteria Efficiently Protect Potato Tubers from Soft Rot Disease.

Soft rot Pectobacteriaceae (SRP) are a group of destructive Gram-negative phytopathogens that can infect a wide range of plant hosts, including potatoes. There are no effective control agents available against SRP, making their management challenging. We have developed a novel approach to protect potato tubers against SRP. It makes use of encapsulated predatory Bdellovibrio bacteriovorus bacteria that, upon release from a polymeric carrier, prey upon SRP. We applied a carrageenan-trehalose-based formulation containing a B. bacteriovorus HD100 predator to prevent soft rot disease development in potato tubers, under various conditions. The dried formulation exhibited very high stability over an 18-month period at room temperature (∼25°C), in contrast to unencapsulated suspensions of the predator, in which viability decreased rapidly below detection level. The rehydrated formulation was as efficient as freshly grown unencapsulated predators and provided high protection in potted potato tubers, displaying an average of 50% reduction in disease parameters (e.g., tissue decay and disease index) under controlled conditions at 7 days postinoculation and planting. The protective effect provided by this formulation was maintained in longer-term trials (28 days) conducted in larger vessels within a net house under natural climate conditions, highlighting its potential for practical application in the field.

Aging and Pathological Conditions Similarity Revealed by Meta-Analysis of Metabolomics Studies Suggests the Existence of the Health and Age-Related Metapathway

Background: The incidence of many diseases increases with age and leads to multimorbidity, characterized by the presence of multiple diseases in old age. This phenomenon is closely related to systemic metabolic changes; the most suitable way to study it is through metabolomics. The use of accumulated metabolomic data to characterize this phenomenon at the system level may provide additional insight into the nature and strength of aging–disease relationships. Methods: For this purpose, metabolic changes associated with human aging and metabolic alterations under different pathological conditions were compared. To do this, the published results of metabolomic studies on human aging were compared with data on metabolite alterations collected in the human metabolome database through metabolite set enrichment analysis (MSEA) and combinatorial analysis. Results: It was found that human aging and pathological conditions involve the set of the same metabolic pathways with a probability of 99.96%. These data show the high identity of the aging process and the development of diseases at the metabolic level and allow to identify the set of metabolic pathways reflecting age-related changes closely associated with health. Based on these pathways, a metapathway was compiled, changes in which are simultaneously associated with health and age. Conclusions: The knowledge about the strength of the convergence of aging and pathological conditions has been supplemented by the rigor evidence at the metabolome level, which also made it possible to outline the age and health-relevant place in the human metabolism.

Targeting the NLRP3 inflammasome-IL-1β pathway in type 2 diabetes and obesity.

Increased activity of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome-IL-1β pathway is observed in obesity and contributes to the development of type 2 diabetes and its complications. In this review, we describe the pathological activation of IL-1β by metabolic stress, ageing and the microbiome and present data on the role of IL-1β in metabolism. We explore the physiological role of the IL-1β pathway in insulin secretion and the relationship between circulating levels of IL-1β and the development of diabetes and associated diseases. We highlight the paradoxical nature of IL-1β as both a friend and a foe in glucose regulation and provide details on clinical translation, including the glucose-lowering effects of IL-1 antagonism and its impact on disease modification. We also discuss the potential role of IL-1β in obesity, Alzheimer's disease, fatigue, gonadal dysfunction and related disorders such as rheumatoid arthritis and gout. Finally, we address the safety of NLRP3 inhibition and IL-1 antagonists and the prospect of using this therapeutic approach for the treatment of type 2 diabetes and its comorbidities.

Parkinson's Disease: Unravelling the Medicinal Perspectives and Recent Developments of Heterocyclic Monoamine Oxidase-B Inhibitors.

Parkinson's disease is a neurodegenerative condition characterized by slow movement (bradykinesia), tremors, and muscle stiffness. These symptoms occur due to the degeneration of dopamine- producing neurons in the substantia nigra region of the brain, leading to reduced dopamine levels. The development of Parkinson's Disease (PD) involves a combination of genetic and environmental factors. PD is associated with abnormal regulation of the monoamine oxidase (MAO) enzyme. Monoamine oxidase inhibitors (MAOIs) are an important class of drugs used to treat PD and other neurological disorders. In the early stages of PD, monotherapy with MAO-B inhibitors has been shown to be both safe and effective. These inhibitors are also commonly used as adjuncts in long-term disease management, as they can improve both motor and non-motor symptoms, reduce "OFF" periods, and potentially slow disease progression. However, current MAO-B inhibitors come with side effects like dizziness, nausea, vomiting, light-headedness, and fainting. Therefore, accelerating the development of new MAO-B inhibitors with fewer side effects is crucial. This review explores natural compounds that may inhibit monoamine oxidase B (MAO-B), focusing on key findings from the past seven years. It highlights the most effective heterocyclic compounds against MAO-B, including thiazolyl hydrazone, pyridoxine-resveratrol, pyridazine, isoxazole, oxadiazole, benzothiazole, benzoxazole, coumarin, caffeine, pyrazoline, piperazine, piperidine, pyrrolidine, and morpholine derivatives. The review covers in vitro, in silico, and in vivo data, along with the structure- activity relationship of these compounds. These findings offer valuable insights for the development of more effective MAO-B inhibitors and advancements in Parkinson's disease research.

IL-10 promotes Th17 cell differentiation by enhancing STAT1-dependent IL-6 production via IgE-stimulated mast cells

Mast cells (MCs) are tissue-resident cells of hematopoietic origin that play an important role in host’s defense mechanism against nematodes. However, excessive activation of these cells contributes to the development of certain allergic diseases. Immunoglobin E (IgE) is one of the well-known molecules that activate MCs. Even in the absence of specific antigens, the binding of highly cytokinergic IgE to FcεRI on MCs prolongs their survival and induces cytokine production without enhancing their degranulation. In the present study, we examined the effects of the members of the interleukin-10 (IL-10) family of cytokines on IgE-mediated MCs functions. The receptors including Il10r1, Il10r2, and Il20r2, but not Il20r1, Il22r1 or Il28r1, were constitutively expressed in mouse bone marrow cell-derived cultured MCs (BMCMCs), suggesting that IL-10 may influence MCs function. Indeed, we found that only IL-10 could influence upon BMCMCs function; IL-10 enhanced prolongation of survival, promoted IL-6 and/or IL-13 production dependently of STAT1 and STAT3, and suppressed tumor necrosis factor production independently of STAT1 and STAT3 on IgE-stimulated BMCMCs. Moreover, the IL-10-mediated enhancement of IL-6 production by IgE-stimulated BMCMCs promotes Th17 cell expansion. These results suggest that IL-10 has a dual role as an anti-inflammatory and pro-inflammatory cytokine in MCs functions.