Unique roles in health promotion of dietary flavonoids through gut microbiota regulation: Current understanding and future perspectives.
Food chemistry. 2023;:133959
Advances in understanding the biological effects of dietary flavonoids and flavonoid-rich foods have been reported. Improving knowledge about their beneficial effects, and mechanisms of action, is crucial for better utilization. However, mechanisms responsible for their health benefits are still unclear. Previous research considered has suggested that gut microbiota might be linked to the metabolism of dietary flavonoids. To understand the bioactivities of dietary flavonoids/flavonoid-rich foods better, and the role of microbiota, we explored systematically 1) types of dietary flavonoids and associated health benefits, 2) low bioaccessibilities and metabolic characteristics, 3) gut microbiota role in regulation, and 4) crosstalk between regulation mechanisms. Current challenges and future perspectives were also considered, offering new research directions and identifying trends in the development of flavonoid-rich food products.
Exploration of the Specific Pathology of HXMM Tablet Against Retinal Injury Based on Drug Attack Model to Network Robustness.
Frontiers in pharmacology. 2022;:826535
Retinal degenerative diseases are related to retinal injury because of the activation of the complement cascade, oxidative stress-induced cell death mechanisms, dysfunctional mitochondria, chronic neuroinflammation, and production of the vascular endothelial growth factor. Anti-VEGF therapy demonstrates remarkable clinical effects and benefits in retinal degenerative disease patients. Hence, new drug development is necessary to treat patients with severe visual loss. He xue ming mu (HXMM) tablet is a CFDA-approved traditional Chinese medicine (TCM) for retinal degenerative diseases, which can alleviate the symptoms of age-related macular degeneration (AMD) and diabetic retinopathy (DR) alone or in combination with anti-VEGF agents. To elucidate the mechanisms of HXMM, a quantitative evaluation algorithm for the prediction of the effect of multi-target drugs on the disturbance of the disease network has been used for exploring the specific pathology of HXMM and TCM precision positioning. Compared with anti-VEGF agents, the drug disturbance of HXMM on the functional subnetwork shows that HXMM reduces the network robustness on the oxidative stress subnetwork and inflammatory subnetwork to exhibit the anti-oxidation and anti-inflammation activity. HXMM provides better protection to ARPE-19 cells against retinal injury after H2O2 treatment. HXMM can elevate GSH and reduce LDH levels to exhibit antioxidant activity and suppress the expression of IL-6 and TNF-α for anti-inflammatory activity, which is different from the anti-VEGF agent with strong anti-VEGF activity. The experimental result confirmed the accuracy of the computational prediction. The combination of bioinformatics prediction based on the drug attack on network robustness and experimental validation provides a new strategy for precision application of TCM.
Biotic Supplements in Patients With Chronic Kidney Disease: Meta-Analysis of Randomized Controlled Trials.
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2022;(1):10-21
OBJECTIVE Gut flora imbalance characterizes patients with chronic kidney disease (CKD). Although biotic supplementation has been proposed to lessen inflammation and oxidative stress and, thus, reduce the risk of progressive kidney damage and cardiovascular disease, the effects remain controversial. We conducted a meta-analysis to assess the therapeutic benefits of biotics in CKD. METHODS PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials that evaluated any biotic (prebiotic, probiotic, synbiotics) supplements in patients with CKD (CKD, stage 3-4 to end-stage renal disease). Primary endpoints included changes in renal function, markers of inflammation, and oxidative stress. Secondary endpoints included changes in levels of uremic toxins and variations in lipid metabolism. RESULTS Twenty-three eligible studies included 842 participants. In a pooled-analysis, biotics did not change estimated glomerular filtration rate (mean difference [MD] = 0.08, P = .92) or serum albumin (MD = -0.01, P = .86), although prebiotics reduced serum creatinine (standardized mean difference [SMD] = -0.23, P = .009) and blood urea nitrogen (MD = -6.05, P < .00001). Biotics improved total antioxidative capacity (SMD = 0.37, P = .007) and malondialdehyde (SMD = -0.96, P = .006) and reduced the inflammatory marker interleukin-6 (SMD = -0.30, P = .01) although not C-reactive protein (SMD = -0.22, P = .20). Biotic intervention reduced some uremic toxins, including p-cresol sulfate (SMD = -2.18, P < .0001) and indoxyl sulfate (MD = -5.14, P = .0009), which decreased in dialysis-dependent patients. Another toxin, indole-3-acetic acid (MD = -0.22, P = .63), did not change. Lipids were unaffected by biotic intervention (total cholesterol: SMD = -0.01, P = .89; high-density lipoprotein: SMD = -0.08, P = .76; low-density lipoprotein: MD = 3.54, P = .28; triglyceride: MD = -2.26, P = .58). CONCLUSION The results highlight the favorable influence of biotics on circulating markers of creatinine, oxidant stress (malondialdehyde, total antioxidative capacity), inflammation (interleukin-6), and uremic toxins (p-cresol sulfate) in patients with CKD. Biotics did not affect estimated glomerular filtration rate, albumin, indole-3-acetic acid, or lipids in either predialysis or dialysis patients.
Emerging Roles of Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitors in Diabetic Cardiovascular Diseases: Focusing on Immunity, Inflammation and Metabolism.
Frontiers in pharmacology. 2022;:836849
Diabetes mellitus (DM) is one of the most fast evolving global issues characterized by hyperglycemia. Patients with diabetes are considered to face with higher risks of adverse cardiovascular events. Those are the main cause of mortality and disability in diabetes patients. There are novel antidiabetic agents that selectively suppress sodium-glucose cotransporter-2 (SGLT-2). They work by reducing proximal tubule glucose reabsorption. Although increasing evidence has shown that SGLT-2 inhibitors can contribute to a series of cardiovascular benefits in diabetic patients, including a reduced incidence of major adverse cardiovascular events and protection of extracardiac organs, the potential mechanisms of SGLT2 inhibitors' cardiovascular protective effects are still not fully elucidated. Given the important role of inflammation and metabolism in diabetic cardiovascular diseases, this review is intended to rationally compile the multifactorial mechanisms of SGLT-2 inhibitors from the point of immunity, inflammation and metabolism, depicting the fundamental cellular and molecular processing of SGLT-2 inhibitors exerting regulating immunity, inflammation and metabolism. Finally, future directions and perspectives to prevent or delay cardiovascular complications in DM by SGLT-2 inhibitors are presented.
Efficacy and safety of nitrate supplementation on exercise tolerance in chronic obstructive pulmonary disease: A systematic review and meta-analysis.
BACKGROUND Exercise intolerance was prevalent in people with chronic obstructive pulmonary disease (COPD) and had a detrimental effect on the quality of life. We aimed to evaluate the efficacy and safety of nitrate supplementation in exercise tolerance of people with COPD. METHODS We searched medical databases including Cochrane Library, EMBASE, and PubMed from inception to October 2020 for randomized control trials in treating COPD with nitrate supplementation. RESULTS Nine trials were identified. Compared with placebo, nitrate supplementation has no significant effect on the following variables: exercise endurance time (standard mean difference [SMD]: 0.06; 95% confidence interval [CI]: -0.39 to 0.52; P = .79), exercise capacity (SMD: 0.30; 95% CI: -0.21 to 0.80; P = .25), oxygen consumption (SMD: -0.04; 95% CI: -0.33 to 0.25; P = .80), resting systolic blood pressure (MD: -2.84; 95% CI: -8.46 to 2.78; P = .32), systolic blood pressure after exercise (MD: -4.66; 95% CI -15.66 to 6.34; P = .41), resting diastolic blood pressure (MD: 0.89; 95% CI: -4.41 to 6.19; P = .74), diastolic blood pressure after exercise (MD: -0.21; 95% CI: -5.51 to 5.10; P = .94), heart rate (MD: -2.52; 95% CI: -7.76 to 2.73; P = .35), and arterial oxygen saturation (MD: -0.44; 95% CI: -2.38 to 1.49; P = .65). No severe adverse effects from nitrate supplementation were reported in the included trails. CONCLUSION Current evidence suggests that nitrate supplementation may be safe but ineffective for improving exercise tolerance in people with COPD.
Targeting the innate immune system with nanoparticles for cancer immunotherapy.
Journal of materials chemistry. B. 2022;(11):1709-1733
Various cancer therapies have advanced remarkably over the past decade. Unlike the direct therapeutic targeting of tumor cells, cancer immunotherapy is a new strategy that boosts the host's immune system to detect specific cancer cells for efficient elimination. Unfortunately, the efficacy of these treatments has been limited to a fraction of patients within a subset of tumor types, and further studies are still needed to clarify these mechanisms and develop novel approaches to improve the efficacy of cancer immunotherapy. Emerging data suggest that the innate immune system also plays a key role in tumor immunosurveillance and generation of antitumor immune responses. Nanoparticles incorporating immunomodulatory agents can activate immune cells and modulate the tumor microenvironment to enhance antitumor immunity. Such nanoparticle-based cancer immunotherapies have received considerable attention and have been extensively studied in recent years. In this review, we will discuss the anticancer activities of nanoparticles designed to target innate immune pathways, including Toll-like receptor, nucleotide-binding oligomerization domain-like receptor, and retinoic acid-inducible gene-I-like receptor pathways, as well as DNA sensing pathways. In addition, nanoparticles that target key innate immune cell types, such as macrophages, myeloid-derived suppressor cells, dendritic cells, natural killer cells, and neutrophils, also will be investigated. In summary, although further research and clinical studies are still needed to solve the safety concerns and improve the efficacy of nanoplatform-based cancer immunotherapy, the recent studies presented in this review prove that nanoparticle-incorporated cancer immunotherapy is a highly promising treatment for cancer patients.
TaNBR1, a Novel Wheat NBR1-like Domain Gene Negatively Regulates Drought Stress Tolerance in Transgenic Arabidopsis.
International journal of molecular sciences. 2022;(9)
Drought stress is an important factor that severely affects crop yield and quality. Autophagy has a crucial role in the responses to abiotic stresses. In this study, we explore TaNBR1 in response to drought stress. Expression of the TaNBR1 gene was strongly induced by NaCl, PEG, and abscisic acid treatments. The TaNBR1 protein is localized in the Golgi apparatus and autophagosome. Transgenic Arabidopsis plants overexpressing TaNBR1 exhibited reduced drought tolerance. When subjected to drought stress, compared to the wild-type (WT) lines, the transgenic overexpressing TaNBR1 plants had a lower seed germination rate, relative water content, proline content, and reduced accumulation of antioxidant enzymes, i.e., superoxide dismutase, peroxidase, and catalase, as well as higher chlorophyll losses, malondialdehyde contents, and water loss. The transgenic plants overexpressing TaNBR1 produced much shorter roots in response to mannitol stress, in comparison to the WT plants, and they exhibited greater sensitivity to abscisic acid treatment. The expression levels of the genes related to stress in the transgenic plants were affected in response to drought stress. Our results indicate that TaNBR1 negatively regulates drought stress responses by affecting the expression of stress-related genes in Arabidopsis.
Effects of Xinkeshu tablets on coronary heart disease patients combined with anxiety and depression symptoms after percutaneous coronary intervention: A meta-analysis.
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2022;:154243
BACKGROUND Xinkeshu tablets (XKS), a well-known Chinese patent drug, have been administered to coronary heart disease (CHD) patients with anxiety and depression after percutaneous coronary intervention (PCI). PURPOSE This meta-analysis aimed to systematically evaluate the clinical effects of XKS for treating CHD patients with anxiety and depression after PCI. METHODS Randomized controlled trials (RCTs) about XKS alone or combined with conventional drugs for the treatment of CHD patients with anxiety and depression after PCI were retrieved from 7 databases (MEDLINE, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP) Database, Chinese Biomedical Database (CBM) and Wanfang Database) through November 2021. First, the studies were reviewed and screened by two independent assessors according to the eligibility criteria. Second, the methodological quality of the eligible studies was evaluated based on the Cochrane Collaboration's tool for assessing the risk of bias. Subsequently, meta-analysis was performed by using RevMan 5.4 software, and publication bias was evaluated by Stata 12.0 software. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the quality of the evidence. RESULTS In total, 11 clinical RCTs involving 1000 patients were included in this study. This meta-analysis found that compared with conventional treatment alone, XKS combined with conventional treatment significantly improved the anxiety scale scores (SMD = -1.97, 95% CI -3.13 to -0.82; p = 0.0008; I2 = 98%), the depression scores (SMD = -2.80, 95% CI -4.49 to -1.10; p = 0.001; I2 = 98%), the scores on the Medical Outcomes Study 36 Item Short Form Health Survey (SF36) (MD = 11.22, 95% CI 4.19 to 18.26; p =0.002; I2 = 95%) and the blood lipid levels of total cholesterol (TC) (MD = -0.38, 95% CI -0.62 to -0.13; p = 0.003; I2 = 0%) and triglyceride (TG) (MD = -0.31, 95% CI -0.46 to -0.17; p < 0.0001; I2 = 0%). CONCLUSION The current evidence suggests that XKS might benefit CHD patients experiencing anxiety and depression after PCI by helping to improve their depression symptoms, TC and TG blood lipid levels. However, due to insufficient methodological quality of the studies, several risks of bias and inadequate reporting of the clinical data, more rigorous, multicenter, sufficient-sample and double-blind randomized clinical trials are warranted.
Effects of Vitamin D on Respiratory Function and Immune Status for Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.
Computational and mathematical methods in medicine. 2022;:2910782
Background: Many studies have demonstrated that vitamin D has clinical benefits when used to treat patients with chronic obstructive pulmonary disease (COPD). However, most of these studies have insufficient samples or inconsistent results. The aim of this meta-analysis was to evaluate the effects of vitamin D therapy in patients with COPD. Methods: We performed a comprehensive retrieval in the following electronic databases: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journals Database (VIP). Two trained reviewers identified relevant studies, extracted data information, and then assessed the methodical quality by the Cochrane risk of bias assessment tool, independently. Then, the meta-analyses were conducted by RevMan 5.4, binary variables were represented by risks ratio (RR), and continuous variables were represented by mean difference (MD) or standardized mean difference (SMD) to assess the efficacy of vitamin D therapy in patients with COPD. Then, publication bias assessment was conducted by funnel plot analysis. Finally, the quality of evidence was assessed by the GRADE system. Results: A total of 15 articles involving 1598 participants were included in this study. The overall results showed a statistical significance of vitamin D therapy in patients with COPD which can significantly improve forced expiratory volume in 1 second (FEV1) (MD: 5.69, 95% CI: 5.01-6.38,P < 0.00001,I2 = 51%) and FEV1/FVC (SMD:0.49, 95% CI: 0.39-0.60,P < 0.00001,I2 = 84%); and serum 25 (OH)D (SMD:1.21, 95% CI:1.07-1.34,P < 0.00001,I2 = 98%) also increase CD3+ Tcells (MD: 6.67, 95% CI: 5.34-8.00,P < 0.00001,I2 = 78%) and CD4+ T cells (MD: 6.00, 95% CI: 5.01-7.00,P < 0.00001,I2 = 65%); and T lymphocyte CD4+/CD8+ ratio (MD: 0.41, 95% CI: 0.20-0.61,P = 0.0001,I2 = 95%) obviously decrease CD8+ Tcells(SMD: -0.83, 95% CI: -1.05- -0.06,P < 0.00001,I2 = 82%), the times of acute exacerbation (RR: 0.40, 95% CI: 0.28-0.59,P < 0.00001,I2 = 0%), and COPD assessment test (CAT) score (MD: -3.77, 95% CI: -5.86 - -1.68,P = 0.0004,I2 = 79%). Conclusions: Our analysis indicated that vitamin D used in patients with COPD could improve the lung function (FEV1 and FEV1/FVC), the serum 25(OH)D, CD3+ T cells, CD4 + T cells, and T lymphocyte CD4+/CD8+ ratio and reduce CD8+ T cells, acute exacerbation, and CAT scores.
Association of MTHFR 677C > T gene polymorphism with neonatal defects: a meta-analysis of 81444 subjects.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2022;(6):1811-1822
This meta-analysis was performed to clarify controversial associations of the MTHFR 677 C > T gene polymorphism in maternal and foetal tissue with neonatal defects. It was reported the association of MTHFR 677 C > T gene polymorphism with frequencies of neonatal defects including congenital heart disease (CHD), neural tube defects (NTD), non-syndromic cleft lip and palate (NSCL/P), and Down syndrome (DS). Depending on the neonatal defect subtypes, MTHFR 677 C > T gene polymorphism was associated with NTD, CHD (except for codominant mode of inheritance (TC/CC) and dominant mode of inheritance (TT + TC/CC); p = .167 and p = .054, respectively), DS, and NSCL/P (codominant mode of inheritance (TC/CC), p = .032) in the maternal group. However, in the neonatal group, the MTHFR 677 C > T gene polymorphism was only associated with the frequency of NTD and CHD. Maternal and neonatal MTHFR 677 C > T gene polymorphisms appear to be associated with neonatal defects but differ by defect types.IMPACT STATEMENTWhat is already known on this subject? Neonatal defects are a signifcant problem and are related to genes involved in the metabolism of homocysteine and folate.What do the results of this study add? The MTHFR 677C > T polymorphism in maternal and neonatal subjects was significantly associated with neonatal defects. When the neonatal subjects were stratified based on disease, the maternal MTHFR 677C > T polymorphism was found to be significantly correlated with all four neonatal defects. In contrast, the polymorphism in newborns was significantly associated with neural tube defects.What are the implications of these findings for clinical practice and/or further research? We believe that our study makes a significant contribution to the literature because it collectively analysed neural tube defects, congenital heart disease, cleft lip and palate, and Down syndrome in relation to the 677C > T polymorphism of MTHFR. Thus, we anticipate that this study will serve as a valuable resource for future investigations of neonatal defect prevention and maternal inheritance in newborn diseases.