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Clinical Epigenetics Jun 2024Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a... (Review)
Review
BACKGROUND
Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes.
MAIN BODY
By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions.
CONCLUSION
The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.
Topics: Humans; Gastrointestinal Neoplasms; Epigenesis, Genetic; Major Histocompatibility Complex; Gene Expression Regulation, Neoplastic; Immunotherapy; DNA Methylation; Tumor Escape
PubMed: 38915093
DOI: 10.1186/s13148-024-01698-8 -
Parasitology Research Jun 2024Sterol 14-demethylase (CYP51) inhibitors, encompassing new chemical entities and repurposed drugs, have emerged as promising candidates for Chagas disease treatment,... (Meta-Analysis)
Meta-Analysis Review
Sterol 14-demethylase (CYP51) inhibitors, encompassing new chemical entities and repurposed drugs, have emerged as promising candidates for Chagas disease treatment, based on preclinical studies reporting anti-Trypanosoma cruzi activity. Triazoles like ravuconazole (RAV) and posaconazole (POS) progressed to clinical trials. Unexpectedly, their efficacy was transient in chronic Chagas disease patients, and their activity was not superior to benznidazole (BZ) treatment. This paper aims to summarize evidence on the global activity of CYP51 inhibitors against T. cruzi by applying systematic review strategies, risk of bias assessment, and meta-analysis from in vivo studies. PubMed and Embase databases were searched for original articles, obtaining fifty-six relevant papers meeting inclusion criteria. Characteristics of animal models, parasite strain, treatment schemes, and cure rates were extracted. Primary outcomes such as maximum parasitaemia values, survival, and parasitological cure were recorded for meta-analysis, when possible. The risk of bias was uncertain in most studies. Animals treated with itraconazole, RAV, or POS survived significantly longer than the infected non-treated groups (RR = 4.85 [3.62, 6.49], P < 0.00001), and they showed no differences with animals treated with positive control drugs (RR = 1.01 [0.98, 1.04], P = 0.54). Furthermore, the overall analysis showed that RAV or POS was not likely to achieve parasitological cure when compared with BZ or NFX treatment (OD = 0.49 [0.31, 0.77], P = 0.002). This systematic review contributes to understanding why the azoles had failed in clinical trials and, more importantly, how to improve the animal models of T. cruzi infection by filling the gaps between basic, translational, and clinical research.
Topics: Animals; Humans; 14-alpha Demethylase Inhibitors; Chagas Disease; Disease Models, Animal; Sterol 14-Demethylase; Thiazoles; Treatment Outcome; Triazoles; Trypanocidal Agents; Trypanosoma cruzi
PubMed: 38904688
DOI: 10.1007/s00436-024-08257-3 -
The British Journal of General Practice... Jun 2024Fractional exhaled nitric oxide (FeNO) as a predictor of inhaled corticosteroid (ICS) response in asthma has been established. However, the same has not been established... (Review)
Review
BACKGROUND
Fractional exhaled nitric oxide (FeNO) as a predictor of inhaled corticosteroid (ICS) response in asthma has been established. However, the same has not been established in chronic obstructive pulmonary disease (COPD). An optimal value of FeNO for prescribing and monitoring ICS response has not been quantified.
AIM
To examine the evidence for this association.
METHOD
A systematic review was conducted of randomised controlled trials and observational studies examining the association between FeNO level and response to ICS in COPD patients. All studies examining this association were included. Five databases were searched thoroughly. Systematic screening, full-text reviews, and data extraction were carried out based on eligibility criteria.
RESULTS
A total of 8690 studies were identified, 342 texts were screened fully, and six studies were included for the final review. One was a randomised controlled trial and the other five were non-randomised interventional trials. One study was conducted in asthma-COPD overlap (ACO patients). After ICS use, three studies found statistically significant correlations between FeNO and lung function improvement (FEV1), and three studies also found significant correlations between FeNO and COPD quality-of-life scores.
CONCLUSION
Measurement of FeNO is non-invasive and standardised, with results available at the point of testing. Because of the small sample size and short duration of studies, exacerbation frequencies were not measured. Despite this, the review suggests that FeNO may be a potential biomarker for assessing ICS response in COPD. Further research that stratifies patients by FeNO levels and assesses the impact on acute exacerbations is needed to understand its potential value in routine clinical practice.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Administration, Inhalation; Adrenal Cortex Hormones; Nitric Oxide; Fractional Exhaled Nitric Oxide Testing; Treatment Outcome; Quality of Life; Randomized Controlled Trials as Topic; Forced Expiratory Volume; Asthma; Breath Tests
PubMed: 38902064
DOI: 10.3399/bjgp24X737745 -
Diabetes, Obesity & Metabolism Jun 2024To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [neuropathy, retinopathy,...
Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all-cause mortality in adults, compared with bisphosphonates: An analysis of real-world, cohort data, with a systematic review and meta-analysis.
AIM
To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all-cause mortality) in patients with T2D, before (iii) combining results with prior studies using meta-analysis.
METHODS
A retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) was conducted from 331 375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n = 45 854) or bisphosphonates (control, n = 285 521), across 83 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 45 851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long-term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed the association between denosumab and T2D. Estimates were pooled using random-effects meta-analysis. Risk of bias and evidence quality were assessed using Cochrane-endorsed tools.
RESULTS
Denosumab (vs. bisphosphonates) was associated with a lower risk of incident T2D over 5 years (hazard ratio 0.83 [95% confidence interval {CI} 0.78-0.88]). Secondary analysis showed significant risk reduction in all-cause mortality (0.79 [0.72-0.87]) and foot ulceration (0.67 [0.53-0.86]). Also, pooled results from four studies (three observational, one randomized controlled trial) following meta-analysis showed a reduced relative risk (RR [95% CI]) for incident T2D in patients prescribed denosumab (0.83 [0.79-0.87]) (I = 10.76%).
CONCLUSIONS
This is the largest cohort study to show that denosumab treatment is associated with a reduced RR of incident T2D, as well as an associated reduced RR of all-cause mortality and microvascular complications, findings that may influence guideline development in the treatment of osteoporosis, particularly in patients who are at a high risk of T2D.
PubMed: 38899553
DOI: 10.1111/dom.15708 -
Frontiers in Endocrinology 2024There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM)...
There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using "smart pumps" or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L), although any form of carbohydrate (e.g., sucrose, which consists of glucose and fructose, or honey, sugary soft drinks, or fruit juice) containing glucose may be used. Using automatic insulin delivery systems, the oral glucose dose can be decreased to 0.1 g/kg. Practical flow charts are included to aid clinical decision-making. Although representing the official position of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED), these guidelines are applicable to the global audience and are especially pertinent in the era of CGM and other advanced technologies.
Topics: Humans; Hypoglycemia; Child; Adolescent; Blood Glucose Self-Monitoring; Insulin; Hypoglycemic Agents; Blood Glucose; Diabetes Mellitus, Type 1; Insulin Infusion Systems; Risk Assessment; Practice Guidelines as Topic; Disease Management
PubMed: 38894740
DOI: 10.3389/fendo.2024.1387537 -
Molecules (Basel, Switzerland) May 2024Chronic kidney disease (CKD) presents a formidable global health concern, affecting one in six adults over 25. This review explores the potential of phenolic compounds... (Review)
Review
Chronic kidney disease (CKD) presents a formidable global health concern, affecting one in six adults over 25. This review explores the potential of phenolic compounds in managing CKD and its complications. By examining the existing research, we highlight their diverse biological activities and potential to combat CKD-related issues. We analyze the nutritional benefits, bioavailability, and safety profile of these compounds. While the clinical evidence is promising, preclinical studies offer valuable insights into underlying mechanisms, optimal dosages, and potential side effects. Further research is crucial to validate the therapeutic efficacy of phenolic compounds for CKD. We advocate for continued exploration of their innovative applications in food, pharmaceuticals, and nutraceuticals. This review aims to catalyze the scientific community's efforts to leverage phenolic compounds against CKD-related challenges.
Topics: Humans; Renal Insufficiency, Chronic; Phenols; Animals; Dietary Supplements; Biological Availability
PubMed: 38893451
DOI: 10.3390/molecules29112576 -
Nutrients May 2024(1) Background: The effect of garlic on glucose and lipid metabolism in humans remains controversial. The aim of this study was to investigate the effects of garlic on... (Meta-Analysis)
Meta-Analysis Review
(1) Background: The effect of garlic on glucose and lipid metabolism in humans remains controversial. The aim of this study was to investigate the effects of garlic on blood lipid levels and glucose levels in humans through a systematic review and meta-analysis. (2) Methods: We extensively searched four databases, including PubMed, Web of Science, Embase, and the Cochrane Library, up to February 2024. To assess the collective impact of garlic and its supplements on fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), an analysis was conducted using a random effects model. Subgroup analyses were performed when < 50%. (3) Result: We found that the garlic intervention was effective in controlling FBG (mean difference = -7.01; 95% CI: -8.53, -5.49, < 0.001), HbA1c (mean deviation = -0.66; 95% CI: -0.76, -0.55, < 0.001, = 62.9%), TC (mean difference = -14.17; 95% CI: -19.31, -9.03, < 0.001), and LDL-C (mean difference = -8.20; 95% CI: -15.58, -0.81, = 0.03); moreover, it also increased the level of HDL-C in humans (mean difference = 2.06; 95% CI: 1.54, 2.59; < 0.001). Nonetheless, the intervention involving garlic did not yield a substantial impact on triglyceride (TG) levels. (4) Conclusion: The intervention of garlic is beneficial to control blood glucose and blood lipids in humans.
Topics: Garlic; Humans; Blood Glucose; Randomized Controlled Trials as Topic; Lipids; Glycated Hemoglobin; Dietary Supplements; Triglycerides; Female; Male; Cholesterol, HDL; Middle Aged; Adult
PubMed: 38892625
DOI: 10.3390/nu16111692 -
Nutrients May 2024Gut microbiome-modulating agents (MMAs), including probiotics, prebiotics, postbiotics, and synbiotics, are shown to ameliorate type 1 diabetes (T1D) by restoring the... (Meta-Analysis)
Meta-Analysis Review
Gut microbiome-modulating agents (MMAs), including probiotics, prebiotics, postbiotics, and synbiotics, are shown to ameliorate type 1 diabetes (T1D) by restoring the microbiome from dysbiosis. The objective of this systematic review and meta-analysis was to assess the impact of MMAs on hemoglobin A1c (HbA1c) and biomarkers associated with (T1D). A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, National Knowledge Infrastructure, WeiPu, and WanFang Data up to 30 November 2023. Ten randomized controlled trials ( = 630) were included, with study quality evaluated using the Cochrane risk-of-bias tool. Random-effect models with standardized mean differences (SMDs) were utilized. MMA supplementation was associated with improvements in HbA1c (SMD = -0.52, 95% CI [-0.83, -0.20]), daily insulin usage (SMD = -0.41, 95% confidence interval (CI) [-0.76, -0.07]), and fasting C-peptide (SMD = 0.99, 95% CI [0.17, 1.81]) but had no effects on FBG, CRP, TNF-α, IL-10, LDL, HDL, and the Shannon index. Subgroup analysis of HbA1c indicated that a long-term intervention (>3 months) might exert a more substantial effect. These findings suggest an association between MMAs and glycemic control in T1D. Further large-scale clinical trials are necessary to confirm these findings with investigations on inflammation and gut microbiota composition while adjusting confounding factors such as diet, physical activity, and the dose and form of MMA intervention.
Topics: Diabetes Mellitus, Type 1; Humans; Gastrointestinal Microbiome; Randomized Controlled Trials as Topic; Glycated Hemoglobin; Probiotics; Prebiotics; Biomarkers; Synbiotics; Dietary Supplements; Female; Dysbiosis; Adult; Male
PubMed: 38892608
DOI: 10.3390/nu16111675 -
Nutrients May 2024This systematic review evaluates the hypothesis that optimal serum magnesium levels may enhance remission rates in Crohn's disease (CD) and considers whether magnesium... (Review)
Review
This systematic review evaluates the hypothesis that optimal serum magnesium levels may enhance remission rates in Crohn's disease (CD) and considers whether magnesium supplementation could be beneficial in CD management. This review aims to synthesize available evidence concerning the impact of serum magnesium on disease remission in CD, and to analyze the effectiveness and mechanistic roles of magnesium supplementation. Adhering to the PRISMA guidelines, we searched PubMed, Web of Science, and Scopus up to January 2024 using MeSH terms and free-text queries related to CD and magnesium. The inclusion criteria were studies that investigated serum magnesium levels, effects of supplementation, and the inflammatory mechanisms in CD remission. From the 525 records identified, eight studies met the inclusion criteria after the removal of duplicates and irrelevant records. These studies, conducted between 1998 and 2023, involved a cumulative sample of 453 patients and 292 controls. Key findings include significantly lower serum magnesium levels in CD patients (0.79 ± 0.09 mmol/L) compared to controls (0.82 ± 0.06 mmol/L), with up to 50% prevalence of hypomagnesemia in CD patients observed in one study. Notably, CD patients, particularly men, exhibited lower magnesium intake (men: 276.4 mg/day; women: 198.2 mg/day). Additionally, low magnesium levels correlated with increased sleep latency (95% CI -0.65 to -0.102; = 0.011) and decreased sleep duration (95% CI -0.613 to -0.041; = 0.028). Another key finding was the significant association between low serum magnesium levels and elevated CRP levels as an indicator of CD disease activity. The findings support the hypothesis that serum magnesium levels are significantly lower in CD patients compared to healthy controls and suggest that magnesium supplementation could improve CD management by enhancing remission rates and sleep quality. However, more rigorous, evidence-based research is necessary to define specific supplementation protocols and to fully elucidate the role of magnesium in CD pathophysiology.
Topics: Humans; Crohn Disease; Magnesium; Dietary Supplements; Female; Remission Induction; Male; Adult; Magnesium Deficiency
PubMed: 38892595
DOI: 10.3390/nu16111662 -
Nutrients May 2024Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate,... (Review)
Review
Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.
Topics: Humans; Biological Products; Liver Neoplasms; Apoptosis; Signal Transduction; Antineoplastic Agents; Animals; Antineoplastic Agents, Phytogenic; Autophagy
PubMed: 38892575
DOI: 10.3390/nu16111642