Preclinical studies of natural flavonoids in inflammatory bowel disease based on macrophages: a systematic review with meta-analysis and network pharmacology.

Flavonoid is a category of bioactive polyphenolic compounds that are extensively distributed in plants with specific pharmacological properties, such as anti-inflammatory and anti-oxidant. Importantly, natural flavonoids have shown the protected function on the dextran sulfate sodium (DSS)-induced colitis in animals and lipopolysaccharides (LPS)-induced inflammatory response in macrophages. The purpose of this systematic review is to explore the efficacy of natural flavonoids in animal models of IBD (inflammatory bowel disease) and potential mechanisms in macrophages by meta-analysis and network pharmacology in preclinical studies. Relevant foundation studies were searched from January 2010 to November 2023 in databases like PubMed, Elsevier ScienceDirect, and Web of Science. Then, OriginPro software was used to extract values from images, and the analysis was performed using Review Manager 5.3. The retrieved data was analyzed according to the fixed-effects model and random-effects model. Subsequently, heterogeneity was evaluated using the I2 statistics. Lastly, network pharmacology was applied to confirm mechanisms of natural flavonoids on IBD. According to the results of meta-analysis, we found the natural flavonoids exhibited powerful therapeutic effects against IBD, which not only reversed colonic shortness (WMD = 1.33, 95% CI (1.07, 1.59), P < 0.00001), but also reduced histological score (SMD = - 2.66, 95% CI (- 3.77, - 1.95), P < 0.00001) between natural flavonoid treatment groups compared with the experimental IBD model. Furthermore, treatment with natural flavonoids decreased the levels of tumor necrosis factor-α (TNF-α) in macrophages. Mechanistically, our summarized data substantiate that natural flavonoids alleviate LPS-induced M1 macrophage polarization, anti-oxidant, anti-inflammatory, maintain intestinal barrier, and inhibit the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. Moreover, the results of network pharmacology also support this. This systematic review demonstrated the efficiency of natural flavonoids in treating IBD in preclinical research by meta-analysis and network pharmacology, which offered supporting evidence for clinical trial implementation. However, some limitations remain present, such as technique quality shortage, missed reports on account of negative results, failure to count sample size, and the risk of bias.

TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression.

Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.

Does Routine Anti-Osteoporosis Medication Lower the Risk of Fractures in Male Subjects? An Updated Systematic Review With Meta-Analysis of Clinical Trials.

Background: Several epidemiological articles have reported the correlations between anti-osteoporosis medication and the risks of fractures in male and female subjects, but the specific efficacy of anti-osteoporosis medication for male subjects remains largely unexplored. Objective: The aim of this study was to evaluate the correlation between anti-osteoporosis medication and the risk of fracture in relation to low bone mass [including outcomes of osteoporosis, fracture, and bone mineral density (BMD) loss] in male subjects analyzed in studies within the updated literature. Methods: Randomized controlled trials (RCTs) that analyzed the effectiveness of a treating prescription for male subjects with osteoporosis (or low BMD) and that focused on the outcomes of fracture were included. Relevant studies from Embase, Web of Science, PubMed, and Chinese database of CNKI were retrieved from inception to January 30th, 2019. Two staff members carried out the eligibility assessment and data extraction. The discrepancies were settled by consultation with another researcher. We calculated the pooled relative risks (RRs) based on 95% confidence intervals (CIs). Results: Twenty-seven documents (28 studies) with 5,678 subjects were identified. For the category of bisphosphonates, significant results were observed in pooled analyses for decreased risk of the vertebral fracture domain (RR, 0.44 [95% CI, 0.31-0.62]), nonvertebral fracture domain (RR, 0.63 [95% CI, 0.46-0.87]), and clinical fracture domain (RR, 0.59 [95% CI, 0.48-0.72]) compared with those of controls. Participants with bisphosphonates had a 56% (95% CI = 38-69%) lower risk of vertebral fractures, 37% (95% CI = 13-54%) lower risk of nonvertebral fractures, and 41% (95% CI = 28-52%) lower risk of clinical fractures. Furthermore, meta-analyses also demonstrated a decreased risk of the vertebral fracture domain via treatment with risedronate (RR, 0.45 [95% CI, 0.28-0.72]) and alendronate (RR, 0.41 [95% CI, 0.23-0.74]), but not with calcitriol, calcitonin, denosumab, ibandronate, monofluorophosphate, strontium ranelate, teriparatide, or zoledronic acid, compared with that of controls. Conclusions: This systematic review confirms that bisphosphonates were connected with a decreased risk of vertebral fractures, nonvertebral fractures, and clinical fractures for male subjects with osteoporosis. Future research is needed to further elucidate the role of nonbisphosphonates in treating fractures of osteoporosis subjects.

Can increasing the prevalence of vegetable-based diets lower the risk of osteoporosis in postmenopausal subjects? A systematic review with meta-analysis of the literature.

OBJECTIVES: Several epidemiological investigations have assessed the association between vegetable-based diet intake (VDI) and risk of osteoporosis in postmenopausal subjects (OPS), but the outcomes have been inconsistent. We performed a review of the updated literature to evaluate this correlation. METHODS: We searched for relevant studies published in September 2018 or earlier. Two researchers conducted eligibility assessment and data extraction. Discrepancies were resolved through consultation with a third expert. Pooled odds ratios (ORs) were calculated with 95% confidence intervals (CIs). RESULTS: Ten studies, which included 14,247 subjects, were identified. On comparing the highest category of VDI consumption with the lowest category of VDI consumption, the pooled OR for OPS was 0.73 (95% CI = 0.57-0.95), i.e., participants with a higher intake of vegetables had a 27% (95% CI = 5-43%) lower risk of OPS. Significant benefits were found on subgroup analyses of case-control studies (OR, 0.61 [95% CI, 0.48-0.78]), but not on subgroup analyses of cross-sectional studies (OR, 0.82 [95% CI, 0.57-1.16]). The synthesized effect estimates were in the direction of decreased risk of OPS on subgroup analyses of the femoral region (OR, 0.57, 95% CI = 0.41-0.80) and the lumbar spine (OR = 0.55, 95% CI = 0.38-0.81), but not on subgroup analyses of the calcaneus (OR = 0.85, 95% CI = 0.33-2.16) and the lumbar and/or femoral region (OR = 1.04, 95%CI = 0.79-1.38). Positive results were observed on pooled analyses of the Dual energy X-ray absorptiometry (DEXA) measurement method (OR, 0.72 [95% CI, 0.54-0.95]), but not on pooled analyses of the Standardized Quantitative Ultrasound (QUS) measurement method (OR, 0.85 [95% CI, 0.33-2.16]). This might have resulted from a type II error due to wide confidence intervals and less number of included studies. CONCLUSION: This meta-analysis seemingly confirms that higher consumption of VDI was associated with a lower risk of OPS. Taken together, these results highlight the need for future high-quality design-based trials on quantified vegetable intake and OPS.

Can Dietary Intake of Vitamin C-Oriented Foods Reduce the Risk of Osteoporosis, Fracture, and BMD Loss? Systematic Review With Meta-Analyses of Recent Studies.

Background: Several epidemiological studies have been performed to evaluate the association of dietary intake of vitamin C-oriented foods (DIVCF) with risk of fracture and bone mineral density (BMD) loss, but the results remain controversial. Therefore, we conducted a systematic meta-analysis to assess this correlation. Methods: We searched EmBase, PubMed, Web of Science, and the Chinese database CNKI for relevant articles published up to August 2019. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random- or fixed-effects model. Discrepancies were resolved by consultation with a third expert. Results: A total of 13 eligible articles (including 17 studies) with 19,484 subjects were identified for the present meta-analysis. The pooled RR of hip fracture for the highest vs. lowest category was 0.66 (95% CI, 0.47-0.94) for DIVCF, i.e., people with a greater frequency of Vitamin C uptake had a 34% (95% CI, 6%-53%) lower prevalence of hip fracture. In subgroup analyses stratified by study design, gender, and age, the negative associations were statistically significant. Furthermore, the statistical analysis of the association between DIVCF and risk of osteoporosis (RR, 0.66; 95% CI, 0.48-0.92), BMD at the lumbar spine (pooled r, 0.15; 95% CI, 0.09-0.23), and BMD at the femoral neck (pooled r, 0.20; 95% CI, 0.11-0.34) showed beneficial effects of DIVCF. Conclusion: Our meta-analysis indicates that DIVCF is negatively associated with the risk of hip fracture, osteoporosis, and BMD loss, suggesting that DIVCF decreases the risk of hip fracture, osteoporosis, and BMD loss.

An exploration of the role of a fish-oriented diet in cognitive decline: a systematic review of the literature.

Epidemiological studies have presented inconsistent evidence of the correlation between a fish-oriented dietary intake (FDI) and the risk of cognitive decline. To address these controversies, we performed this systematic review of prospective studies published in December 2016 and earlier using PubMed, Embase, and Web of Science. Two independent researchers conducted the eligibility assessment and data extraction; all discrepancies were solved by discussion with a third researcher. The pooled relative risks (RRs) focused on the incidence of events were estimated with 95% confidence intervals (CIs). Overall, nine studies containing 28,754 subjects were analyzed. When the highest and lowest categories of fish consumption were compared, the summary RR for dementia of Alzheimer type (DAT) was 0.80 (95%CI = 0.65-0.97); i.e., people with a higher intake of fish had a 20% (95%CI = 3-35%) decreased risk of DAT. Additionally, the dose-response synthesized data indicated that a 100-g/week increase in fish intake reduced the risk of DAT by an additional 12% (RR = 0.88, 95%CI = 0.79-0.99). Non-significant results were observed for the risk of dementia of all causes (DAC) and mild cognitive impairment (MCI). Limited evidence involving heterogeneity was found within subgroups or across studies. In conclusion, this review confirmed that a higher intake of fish could be correlated with a reduced risk of DAT. Further research, especially prospective studies that specifically quantify FDI, will help find a more accurate assessment of the different levels of dietary intake.