Radiotherapy Enhancing and Radioprotective Properties of Berberine: A Systematic Review.

BACKGROUND: Natural compounds such as Berberine (Ber) have been considered due to favorable anticancer properties, low side effects, and availability along with chemotherapy treatments. OBJECTIVES: This study aimed to investigate the radiosensitizing and radioprotective properties of Ber. METHODS: In this systematic review that was performed according to PRISMA 2020 guidelines, we searched the publications before 25 Sep 2023 in Web of Science, PubMed, Scopus, Embase, and Cochrane Library databases. After determining inclusion and exclusion criteria, data were extracted and imported into an Excel form, and the results of the studies were reviewed. RESULTS: Ber by reducing the levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-ß1), and increasing interleukin 10 (IL-10) levels, showed its antioxidant and anti-inflammatory properties against ionizing radiation. Reducing cell cytotoxicity and apoptosis were other radioprotective properties of Ber. Conversely, in cancer cells, Ber, via inducing oxidative stress and accumulation ROS in tumor tissues, inducing DNA damage, mitochondrial dysfunction and hyperpolarization, inducing apoptosis, and cell cycle arrest, inhibits the up-regulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) revealed radiosensitizing properties. CONCLUSION: Ber, via various mechanisms, showed favorable radioprotective and radiosensitizing properties in clinical and experimental studies. However, more clinical studies are needed in this field.

Association Between Gallstone Disease and Risk of Mortality of Cardiovascular Disease and Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Gallstone disease (GD) is increasing in the world and has various complications. OBJECTIVE: This study aims to examine the relationship between GD and the risk of mortality from cardiovascular disease (CVD) and cancer using a systematic review and meta-analysis approach. METHODS: A comprehensive and systematic search was done in various databases, such as Web of Science (WOS), Scopus, MEDLINE/PubMed, Cochrane, and Embase. The search included studies published from 1980 to December 2023. Heterogeneity was assessed using Chi-square, I2, and forest plots, while publication bias was evaluated through Begg's and Egger's tests. All analyses were performed using Stata 15, with statistical significance set at p <0.05. RESULTS: A pooled analysis of five studies involving 161,671 participants demonstrated that individuals with GD had a significantly higher risk of mortality from CVD (RR 1.29, 95% CI: 1.11-1.50, p <0.001). Importantly, no evidence of publication bias was found based on the results of Begg's test (p =0.806) and Egger's test (p =0.138). Furthermore, the pooled analysis of seven studies, encompassing a total of 562,625 participants, indicated an increased risk of cancer mortality among individuals with GD (RR 1.45, 95% CI: 1.16-1.82, p <0.001). Similarly, no publication bias was detected through Begg's test (p =0.133) and Egger's test (p =0.089). CONCLUSION: In this study, the evidence of a significant association between GD and an elevated risk of mortality from CVD and cancer is provided. These findings suggest that implementing targeted interventions for individuals with gallstone disease could reduce mortality rates among these patients.

A Systematic Review and Meta-Analysis of the Effects of Statin Therapy on Heart Transplantation.

BACKGROUND: Most of the mortality after Heart Transplantation (HT) is attributed to severe cardiac allograft vasculopathy (CAV) and rejection. OBJECTIVES: This meta-analysis aimed to investigate the effects of postoperative statin therapy on outcomes (mortality, rejection, and CAV in HT patients). METHODS: This systematic review and meta-analysis was performed on publications between 1980 and October 2023 in Web of Science, Scopus, PubMed, Cochrane, Science Direct, Google Scholar, and Embase databases. Heterogeneity was assessed using Chi-square, I2, and forest plots. Publication bias was evaluated using Begg's and Egger's tests. Analyses were performed in Stata 15 with significance at p < 0.05. RESULTS: This meta-analysis included 17 studies comprising 4,627 participants and conducted between 1995 to 2021. Compared to non-users, the odds of mortality were lower among statin users (OR= 0.49, 95% CI: 0.32-0.75, p < 0.001). The odds of CAV were also reduced with statin use (OR= 0.71, 95% CI: 0.53-0.96, p = 0.027). The odds of rejection were not significantly different (OR= 0.69, 95% CI: 0.41-1.15, p = 0.152). However, rejection odds were lower with statins in RCTs (OR= 0.42, 95% CI: 0.21-0.82, p = 0.012) but not in case-control studies (OR= 0.87, 95% CI: 0.49-1.52, p = 0.615). No publication bias was observed with Begg's test, but Egger's test showed possible bias. CONCLUSION: This meta-analysis found postoperative statin use associated with lower mortality and CAV, but not overall rejection, though RCT subgroup analysis showed decreased rejection with statins. Statin therapy may improve prognosis in HT patients.

A Systematic Review and Meta-analysis of the Relationship between Statin Intake and Esophageal Cancer.

BACKGROUND: Esophageal cancer is a malignant tumor with a low survival rate. Statins, commonly prescribed for their lipid-lowering effects, have been suggested to possess potential chemopreventive properties against various cancers, including esophageal cancer. OBJECTIVES: This systematic review studied the association between statin intake and esophageal cancer. METHODS: To conduct this systematic review and meta-analysis, we reviewed studies published between 1980 and June 2023 in Web of Science (WOS), Embase, MEDLINE/PubMed, Scopus, and Cochrane Library databases according to the PRISMA guidelines. Data extraction, quality assessment, and statistical analyses were performed using predefined protocols. We used various statistical tests conducted by Stata statistical software. Statistical significance was considered significant at p < 0.05. RESULTS: Twenty-one studies were collected and analyzed. The meta-analysis demonstrated that the odds ratio (OR) of esophageal cancer in patients treated with statins was 0.65 (95% CI: 0.57-0.75, p < 0.001) compared to the non-receiving group. The ORs for case-control and cohort studies were 0.67 (95% CI:0.54-0.83, p < 0.001) and 0.62 (95% CI:0.55-0.71, p < 0.001), respectively. The investigation into the relationship between the statins intake and the incidence of esophageal cancer did not reveal any indication of publication bias according to both Begg's test (p = 0.966) and Egger's test (p = 0.113). CONCLUSION: The results revealed that the odds of esophageal cancer in patients treated with statins decreased by 35% compared to patients not treated with statins. However, further well-designed prospective studies are needed to validate these findings and understand the underlying mechanisms of statins in preventing esophageal cancer.

The Effects and Safety of Silymarin on ß-thalassemia in Children and Adolescents: A Systematic Review based on Clinical Trial Studies.

BACKGROUND: ß-thalassemia imposes significant complications on affected patients. Silymarin, a natural flavonoid complex, has potential therapeutic properties. OBJECTIVE: This systematic review aims to comprehensively evaluate the literature on the mechanistic effects of Silymarin on ß-thalassemia outcomes in children and adolescents. METHODS: A systematic search of electronic databases, including MEDLINE/PubMed, Embase, Scopus, Cochrane Library, and Web of Science (WOS), was done to identify relevant clinical trials before January 2024. Various data were extracted, including study characteristics, outcomes measured (hematological parameters, oxidative stress markers, iron metabolism, and other outcomes), proposed mechanisms, and safety. RESULTS: By iron chelation effects, Silymarin can reduce reactive oxygen species (ROS) production, increase intracellular antioxidant enzyme glutathione (GSH), and insert antioxidant effects. It also attenuated inflammation through reduced tumor necrosis factor-alpha (TNF-α), transforming growth factor-ß1 (TGF-ß1), interferon-gamma (IFNγ), C-reactive protein (CRP), interleukin 6 (IL-6), IL-17, and IL-23 levels and increase in IL-4 and IL-10 levels. By reducing iron overload conditions, Silymarin indicates modulatory effects on immune abnormalities, inhibits red blood cell (RBC) hemolysis, increases RBC count, and minimizes the need for a transfusion. Moreover, it reduces myocardial and hepatic siderosis, improves liver function tests, and modifies abnormal enzymes, particularly for aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, and total protein levels. Silymarin also reduces iron overload, increases antioxidant and anti-inflammatory capacity in cardiomyocytes, and reveals antioxidant effects. CONCLUSION: Silymarin indicates promising effects on various aspects of children and adolescents with ß-thalassemia and has no serious side effects on the investigated dosage.

The Association between Use of Renin-Angiotensin-Aldosterone System Inhibitors and the Risk and Mortality of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Pancreatic Cancer (PC) is one of the most malignant tumors and highly invasive neoplasms around the world. OBJECTIVE: This systematic review and meta-analysis aims to study the relationship between the use of renin-angiotensin-aldosterone system inhibitors and the incidence and mortality of PC. METHODS: The electronic search was conducted systematically until October 10, 2023. in databases, including Scopus, Web of Science (WOS), PubMed/MEDLINE, Cochrane Library, and Embase. The required data were extracted from the articles and were analyzed by Stata 15 using statistical tests (Chi-square and I2), Forest plots, and publication bias tests (Begg's and Egger's tests). RESULTS: A total of four studies (2011-2019; n=314,856) investigated the relationship between RAS antagonists and PC risk. No significant associations were found between angiotensin receptor blockers (ARBs) (OR=0.94, 95% CI: 0.77-1.14, p=0.513), angiotensin-converting enzyme inhibitors (ACEIs) (OR=0.96, 95% CI: 0.84-1.09, p=0.505), or combination therapy (ARBs + ACEIs) (OR=0.97, 95% CI: 0.87-1.09, p=0.627) and PC risk. Also, nine studies (2010-2023; n=20,483) examined the association between renin-angiotensin-aldosterone system inhibitors and PC mortality. Significant reductions in PC mortality were found for ARBs (OR=0.81, 95% CI: 0.66-0.98, p=0.032), ACEIs (OR=0.89, 95% CI: 0.80-0.99, p=0.038), and combination therapy (OR=0.83, 95% CI: 0.70-0.97, p=0.022). No evidence of publication bias was found in the study results. CONCLUSION: In summary, while renin-angiotensin-aldosterone system inhibitors did not appear to impact PC risk, their use was associated with lower PC mortality based on this meta-analysis of the current evidence. More rigorous and well-designed studies are required to validate and support these findings.

The Relationship between Statin Intake and Risk of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Pancreatic neoplasm is one of the types of cancer with a high incidence and case-fatality rate. OBJECTIVES: This study was designed to investigate the relationship between statin intake and the risk of pancreatic cancer with a systematic review and meta-analysis approach. METHODS: This study was a systematic review and meta-analysis of studies published before 2023 in Cochrane Library, Web of Science (WOS), PubMed, Google Scholar, ScienceDirect, Scopus, and Embase databases. The statistical analyses were conducted using Stata software, version 15. The significance level for this study was set at 0.05. RESULTS: This meta-analysis included 32 studies and a total of 5,849,814 participants. The risk ratio (RR) of pancreatic cancer in comparison to the non-statin receiving group in statin users in total was equal to 0.75 (95% CI: 0.66-0.86, p-value <0.001), in the cohort studies was obtained to be 0.70 (0.53-0.93), in the randomized clinical trials (RCTs) had a ratio of 0.99 (0.53-1.86), while studies conducted in American countries had a ratio of 0.69 (0.51-0.93), studies in Asian countries had a ratio of 0.73 (0.56-0.97), and studies in European countries had a ratio of 0.88 (0.76-1.02). Furthermore, the study did not detect any signs of publication bias. CONCLUSION: The study findings suggest a potential connection between using statins and a lower risk of pancreatic cancer. However, it is important to note that controlled clinical trials did not find a statistically significant association between taking statins and the development of pancreatic cancer. Therefore, it is advisable to exercise caution when interpreting the results of this study.

Effects and Mechanisms of Fisetin Against Ischemia-reperfusion Injuries: A Systematic Review.

BACKGROUND: Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function. OBJECTIVES: This systematic review study investigated fisetin's effects and possible mechanisms in attenuating myocardial, cerebral, renal, and hepatic IRIs. METHODS: This systematic review included studies earlier than Sep 2023 by following the PRISMA statement 2020. After determining inclusion and exclusion criteria and related keywords, bibliographic databases, such as Cochrane Library, PubMed, Web of Science, Embase, and Scopus databases, were used to search the relevant studies. Studies were imported in End- Note X8, and the primary information was recorded in Excel. RESULTS: Fisetin reduced reactive oxygen species (ROS) generation and upregulated antioxidant enzymes, such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx), in ischemic tissues. Moreover, fisetin can attenuate oxidative stress by activating phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Fisetin has been indicated to prevent the activation of several pro-inflammatory signaling pathways, including NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPKs (Mitogen-activated protein kinases). It also inhibits the production of pro-inflammatory cytokines and enzymes like tumor necrosis factor-a (TNF-α), inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-1ß (IL-1ß), IL-1, and IL-6. Fisetin attenuates IRI by improving mitochondrial function, anti-apoptotic effects, promoting autophagy, and preserving tissues from histological changes induced by IRIs. CONCLUSION: Fisetin, by antioxidant, anti-inflammatory, mitochondrial protection, promoting autophagy, and anti-apoptotic properties, can reduce cell injury due to myocardial, cerebral renal, and hepatic IRIs without any significant side effects.

A Systematic Review of the Impact of Resveratrol on Viral Hepatitis and Chronic Viral Hepatitis-related Hepatocellular Carcinoma.

BACKGROUND: Resveratrol (RSV) is used for the treatment of various diseases due to their anti-inflammatory and antioxidant activities. However, its beneficial aspects on viral hepatitis have been less investigated. OBJECTIVE: This report reviews the impact of resveratrol on viral hepatitis and chronic viral hepatitis-related hepatocellular carcinoma (HCC). METHODS: The systematic review was performed and reported according to the PRISMA 2020 statement. Several core databases, such as Cochrane Library, PubMed, Web of Science, EMBASE, and Scopus, were used for search on September 6, 2023. After extraction of the data, the desired information of the full text of the studies was recorded in Excel, and the outcomes and mechanisms were reviewed. RESULTS: RSV inhibits viral replication through anti-HCV NS3 helicase activity, maintains redox homeostasis via glutathione (GSH) synthesis, improves T and B cell activity, and suppresses miR-155 expression. It also enhances viral replication by enhancing hepatitis C virus (HCV) RNA transcription, activating sirtuin-1 (SIRT1), which can increase peroxisome proliferator-activated receptor (PPAR), and SIRT1 activates the HBV X protein (HBx). Moreover, RSV is responsible for hepatitis-related HCC proliferation via suppression of mammalian target of rapamycin (mTOR), SIRT1 up-regulation, inhibiting expression of HBx, and reducing expression of cyclin D1. CONCLUSION: Despite the promising properties of RSV in inhibiting hepatitis-related HCC cell proliferation, its antiviral effects in viral hepatitis are controversial. The antihepatitis behaviors of RSV are mainly dose-dependent, and in some studies, activating some hepatoprotective pathways increases the transcription and replication of chronic HBV and HCV. Therefore, healthcare providers should be aware of viral hepatitis before using RSV supplements.

Anti-seizure Effects and Mechanisms of Berberine: A Systematic Review.

BACKGROUND: Epilepsy is one of the most common in all age groups and disabling neurologic disorders around the world. OBJECTIVES: This systematic review was to explore whether berberine (BBR) has any anti-seizure or anti-epileptic effects and also reviewed this possible mechanism. METHODS: The EMBASE, Scopus, Cochrane Library, PubMed, and Web of Science databases were searched before Sep 2023. All types of studies that investigated the effects of BBR on epilepsy or chemical-induced seizures were eligible for inclusion. Two authors independently evaluated and reviewed titles/abstracts to identify publications for potential eligibility, and a third team member resolved discrepancies. Data were extracted in an Excel form, and the outcomes were discussed. RESULTS: BBR showed its neuroprotective properties by reducing oxidative stress, neuroinflammation, and anti-apoptosis effects. It also increases brain-derived neurotrophic factor (BDNF) release and reduces transforming growth factor-beta (TGF-ß1) and hypoxia-inducible factor 1α (HIF-1α). BBR by increasing scavenging reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2), endogenous antioxidant enzymes, heme oxygenase-1 (HO-1), and inhibition of lipid peroxidation insert its antioxidant activity. Moreover, BBR showed antiinflammatory activity by reducing Interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) levels and through inhibiting cyclooxygenase-2 (COX-2), and including nuclear factor κB (NF-κB). In addition, it modulated c-fos expression and neuronal excitability in the brain. CONCLUSION: BBR indicated promising anti-seizure effects with remarkable antioxidant, antiinflammatory, anti-apoptotic, and neuroprotective activity. Future studies should be based on well-designed clinical trial studies that are integrated with new methods related to increasing bioavailability.

Efficacy and Mechanisms of Silybum Marianum, Silymarin, and Silibinin on Rheumatoid Arthritis and Osteoarthritis Symptoms: A Systematic Review.

BACKGROUND: Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common forms of skeletal disease worldwide. OBJECTIVE: The current systematic review investigated the mechanisms of Silybum marianum, silymarin, and silibinin on RA and OA symptoms. METHODS: The PRISMA 2020 statement was used for reporting Items in this systematic review. The result was a list of five databases, including Web of Science, Cochrane Library, Embase, PubMed, and Scopus. After determining the inclusion and exclusion criteria, of 437 records identified, 21 studies were eligible. The data were extracted from the studies and imported into an Excel form, and finally, the effects, outcomes, and associated mechanisms were surveyed. RESULTS: Silybum marianum and its main constituents revealed immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties in humans and laboratory animals. Moreover, they protect the joints against the cartilage matrix's hypocellularity and fibrillation, reduce synovitis, and inhibit degeneration of aggrecan and collagen-II in human chondrocytes. They also, through reducing inflammatory cytokines, show an analgesic effect. Although silymarin and silibinin have low absorption, their bioavailability can be increased with nanoparticles. CONCLUSION: In experimental studies, Silybum marianum, silymarin, and silibinin revealed promising effects on RA and OA symptoms. However, more clinical studies are needed in this field to obtain reliable results and clinical administration of these compounds.

Statin Use and Hepatocellular Carcinoma Risk: A Comprehensive Meta- Analysis and Systematic Review.

BACKGROUND: Hepatocellular Carcinoma (HCC) is a public health problem around the world. Several studies have investigated the association between statin use and the risk of HCC, however, more studies are needed in this field. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the relationship between statin use and HCC risk. METHODS: Systematic searches of Web of Science, Scopus, PubMed, Cochrane, Science Direct, and Embase were conducted for studies published between 1980 and September 2023. Metaanalyses were performed using Stata 15 with a significance level of 0.05. RESULTS: The search retrieved 8,125 articles, of which 40 were included in the meta-analysis after applying eligibility criteria. The total sample was 5,732,948 participants, including 68,698 HCC cases. Statin use was associated with a 44% lower risk of HCC compared to non-use (RR 0.56, 95% CI 0.50-0.63, p < 0.001). The RR was 0.54 (0.42-0.69) in American countries, 0.52 (0.44-0.62) in Asian countries, and 0.63 (0.48-0.84) in European countries. The RR was 0.50 (0.42-0.60) in studies with a mean age <50 years and 0.61 (0.53-0.70) in studies with a mean age ≥50 years. No evidence of publication bias was found (Begg's test p = 0.718). CONCLUSION: This meta-analysis found statin use is associated with a significantly lower HCC risk. Statins may be a promising preventive intervention against HCC.

The Association between Statins Intake and Risk of Post Stroke Pneumonia: A Systematic Review and Meta-analysis.

AIM: This research aimed to examine the relationship between the intake of statins and the risk of post-stroke pneumonia in a systematic review and meta-analysis study. METHODS: An extensive search of published articles on March 21st , 2023, was done in several databases, like Web of Science (ISI), PubMed, Cochrane Library, Embase, Scopus, and Google Scholar. The Newcastle Ottawa Scale (NOS) checklist was employed to evaluate the quality of observational studies. Statistical tests (Chi-square test and I2 ) and graphical techniques (Forest plot) were used to determine whether heterogeneity existed in the meta-analysis studies. Funnel plots and Begg and Egger's tests were used to assess the publication bias. RESULTS: Seven studies (5 cohort and 2 case-control studies) were retrieved to examine the association between statins and post-stroke pneumonia. The sample size of the studies compiled in the meta-analysis was obtained to be 68,966 participants. Meta-analysis demonstrated that the overall odds of post-stroke pneumonia in the statin group was equal to 0.87 (95% CI: 0.67 - 1.13; p-value 0.458). Subgroup analysis indicated that the odds of post-stroke pneumonia in the statin group was equal to 0.93 (95% CI: 0.73-1.18; p-value=0.558) in the cohort studies, and equal to 0.92 (95% CI: 0.37-2.26; p-value=0.857) in the case-control studies. The examination of the association between the intake of statins and post-stroke pneumonia showed no evidence of publication bias (Begg's test, p-value = 0.368; Eggers test, p-value = 0.282). CONCLUSION: In this study, no relationship has been observed between receiving statins and the risk of post-stroke pneumonia.

A Systematic Review and Meta-analysis on the Role of Statins in the Prevention of Mortality Following Pancreatic Cancer.

BACKGROUND: Pancreatic cancer (PC) is a type of cancer with a high incidence and case-fatality rate. OBJECTIVE: This study aimed to evaluate the role of statins in preventing mortality following PC based on scientific evidence with systematic review and meta-analysis method. METHODS: This meta-analysis considered studies published from 1980 till the end of 2022 in ISI Web of Science, Scopus, PubMed, Cochrane, Science Direct, Google Scholar, and Embase databases. Funnel diagrams and Begg's and Egger's tests were used to assess the publication bias. RESULTS: In general, this meta-analysis has included 19 studies (13 cohort studies, 4 case-control, and 2 randomized clinical trials (RCTs)) and a total of 100,888 patients with PC. The risk of mortality of PC in statin users in total was 0.86 (95% CI: 0.80 - 0.92, P-value <0.001); in the case-control studies, it was equal to 0.53 (0.34-0.83); in the cohort studies, it was equal to 0.87 (0.82-0.92, P-value <0.001); in RCTs, it was equal to 1.19 (0.99-1.42, P-value <0.001); in studies with good quality score category, it was equal to 0.92 (0.86-0.99, P-value <0.001), and in articles of the moderate quality score category, it was equal to 0.73 (0.64-0.84, P-value <0.001). The results of statistical tests indicated the existence of publication bias (Begg's test (P-value = 0.002) and Egger's test (P-value = 0.004)). CONCLUSION: Statins reduce the risk of mortality in patients with PC. However, no significant relation has been observed in RCTs. Therefore, it is necessary to be cautious in interpreting the results.

The Therapeutic Effect of Silymarin and Silibinin on Depression and Anxiety Disorders and Possible Mechanism in the Brain: A Systematic Review.

BACKGROUND: Depression and anxiety are the most common mental disorders worldwide. OBJECTIVE: We aimed to review silymarin and silibinin effects and underlying mechanisms in the central nervous system (CNS) for depression and anxiety treatment. METHODS: The research protocol was prepared based on following the PRISMA statement. An extensive search was done in essential databases such as PubMed, Cochrane Library, Web of Science (ISI), Embase, and Scopus. Considering the study inclusion and exclusion criteria, 17 studies were finally included. The desired information was extracted from the studies and recorded in Excel, and the consequences and mechanisms were reviewed. RESULTS: Silymarin and silibinin upregulated brain-derived neurotrophic factor (BDNF) and improved neural stem cells (NSCs) proliferation in the cortex and hippocampus. They also increased neurochemical serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels. Silymarin and silibinin reduced malondialdehyde (MDA) formation and increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. In addition, silymarin and silibinin reduced interleukin (IL)-6, IL-1ß, and IL-12ß, reducing tumor necrosis factor α (TNF-α) induced neuroinflammation. CONCLUSION: Silymarin and silibinin exert anti-depression and anxiolytic effects by regulating neurotransmitters, endocrine, neurogenesis, and immunologic systems. Therefore, as natural and complementary medicines, they can be used to reduce the symptoms of depression and anxiety; However, more clinical studies are needed in this field.

The Role of Vitamin D in Carpal Tunnel Syndrome Risk and Supplementation Outcomes: A Systematic Review.

BACKGROUND: Carpal tunnel syndrome (CTS) is a debilitating neuropathy that accompanies pain and other physical limitations and disrupts the normal functioning of the victims' lives. OBJECTIVE: We aimed to investigate Vitamin D's preventive and therapeutic effects on the occurrence and remission of CTS symptoms. METHODS: In this systematic review the PRISMA statement has been designed primarily. An extensive search was undertaken in various databases, including PubMed, Cochrane library, Web of Science, EMBASE, and Scopus. After considering the inclusion and exclusion criteria of the study, finally, 19 articles were retrieved. The raw data were extracted and entered into an Excel form, and the study outcomes were investigated. RESULTS: The main symptoms and tests, including functional score, nerve conduction, and pain, were improved after Vitamin D supplementation in CTS patients. However, they revealed worse scores in people with low Vitamin D levels. In addition, the scores of mentioned indices were worsened in people with lower serum Vitamin D levels. Nevertheless, some studies did not find a significant relationship between low serum 25(OH)D and more significant pain scores in CTS patients. In addition, Vitamin D inserts its effects on CTS by regulating cell proliferation, nerve growth factor, suppression of oxidative stress and inflammatory cytokines, and improvement in cartilage and microvascular damage. CONCLUSION: Vitamin D supplementation can improve the symptoms in CTS patients, and low serum 25(OH)D can aggravate the symptoms of the disease and could be a risk factor for its occurrence. However, more observational studies and clinical trials are needed.

Obesity and the Risk of Developing Kidney Stones: A Systematic Review and Meta-analysis.

Obesity is a growing problem that causes various metabolic disorders and organ dysfunction. The present systematic review and meta-analysis examined the impact of obesity on the risk of kidney stones. This meta-analysis was designed according to PRISMA guidelines. This extensive search was conducted on June 6, 2022, using relevant keywords in databases including PubMed, Web of Science, EMBASE, and Scopus. The data collected from observational studies were recorded in a datasheet. Odds Ratio (OR) and their 95% confidence intervals (CI) evaluated the overall effect size. The Cochran Q test and the statistic I2 were used to evaluate the heterogeneity of studies. Egger's and Begg's tests assessed potential publication bias. We included 15 observational studies published between 2005 to 2022 in this analysis. Compared to nonobese individuals, the OR for developing kidney stones in obese participants was 1.35 (95% CI: 1.20 to 1.52, P < .001). Considering geographical location, the OR for the risk of developing kidney stones in obese individuals was 1.51 (95% CI: 1.11 to 2.05, P = .009) in North America, 1.33 (95% CI: 1.16 to 1.51, P < .001) in Europe, and 1.18 (95% CI: 1.08 to 1.29, P < .001) in Asia. Begg's test results (P = .625) demonstrated no publication bias. However, Egger's test results (P = .005) indicated publication bias. Based on the results, obesity increases the risk of kidney stone development. Therefore, community health programs should be implemented to reduce the incidence of obesity and lower the risk of kidney stones.  DOI: 10.52547/ijkd.7223.

Assessment of the Relationship Between Gastric-Acid Suppressants and the Risk of Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis.

Background: Esophageal cancer is a cancerous tumor that develops in the esophagus. It is the 10th most common cancer and has a low survival rate. Esophageal adenocarcinoma (EAC) is increasing in incidence globally. Those with EAC are affected by Barrett's esophagus metaplasia, which is attributed to genetic predisposition and is more common in men. Studies suggest that gastric acid suppressants, like proton pump inhibitors and histamine-2 receptor antagonists, have anticancer properties and reduce EAC. However, other research has suggested that they are not cancer-protective, and the use of antisecretory drugs is a risk factor for developing EAC. Objective: This systematic review and meta-analysis investigated the properties and risk factors associated with using gastric acid suppressants in patients with EAC. Methods: This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Information from selected articles, including the lead author's name, year of publication, study setting, sample size, and gender, was extracted and recorded into an Excel (Microsoft, Redmond, Washington) form. Statistical data included odds ratio, hazard ratio, and/or risk ratio, with a 95% CI associated with patients with EAC and receiving gastric acid suppressants. Data were compared with individuals not receiving treatment. Publication bias was assessed using Begg's and Egger's tests. Statistical analyzes used Stata 14.0 (Stata LLC, College Station, Texas). Results: The initial electronic literature search retrieved 3761 titles/abstracts. Extensive screening selected 20 articles for analysis. Odds ratios associated with EAC in the individuals using gastric acid suppressants were 0.77 (95% CI, 0.49-1.22; P = 0.274) and 0.67 (95% CI, 0.39-1.29; P = 0.240) for proton pump inhibitors and 1.02 (95% CI, 0.44-2.36; P = 0.967) for histamine-2 receptor antagonists. Conclusions: The results found that gastric acid suppressants do not have a protective role in EAC and are not risk factors. Future studies of confounding variables and risk factors are needed to understand what affects EAC development.

Anti-inflammatory response to curcumin supplementation in chronic kidney disease and hemodialysis patients: A systematic review and meta-analysis.

Objective: This study was designed to determine the association curcumin has on pro-inflammatory biomarkers in patients with chronic kidney disease (CKD (and in those receiving hemodialysis (HD). Materials and Methods: This meta-analysis was undertaken following PRISMA guidelines. An extensive systematic review was undertaken until 10/11/2021 using PubMed, Web of Science (ISI), and Scopus databases. The standardized mean difference (SMD) and 95% confidence intervals (CI) were used to estimate the overall effect size of curcumin on serum high-sensitivity C-reactive protein (hs-CRP), and pro-inflammatory cytokines including interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) in patients with CKD and those receiving HD. Results: Overall, ten randomized controlled trials (RCTs) comprising 523 patients were incorporated into the systematic review and meta-analysis. The results showed that when compared with control groups, there was no significant effect observed linking curcumin and IL-6 (SMD = 0.24%, 95% CI = -0.14 to 0.62, p = 0.221), TNF-α (SMD = 0.11%, 95% CI = -0.19 to 0.40, p = 0.480) or hs-CRP (SMD = -0.17%, 95% CI = -0.36 to 0.03, p = 0.093). The analysis determined no publication bias related to the influence of curcumin on IL-6, TNF-α or acute phase reactant, hs-CRP. The Egger's and Begg's test results were not statistically significant (p˃0.20). Conclusion: In patients with CKD and those receiving HD, the use of curcumin supplementation has no statistically significant effect on the anti-inflammatory biomarkers reviewed in this study.

Relationship between serum vitamin D and hip fracture in the elderly: a systematic review and meta-analysis.

INTRODUCTION: This study investigated the relationship between serum 25-hydroxyvitamin D (25OHD) levels and the occurrence of hip fractures in the elderly using a systematic review and meta-analysis approach. MATERIALS AND METHODS: PubMed, Web of Science, and Scopus were used to identify studies that outlined an association between serum 25OHD and the occurrence of a hip fracture in a geriatric patient. The analysis calculated odds ratios (OR) for a hip fracture using a random-effects model. RESULTS: In this study, 28 studies were included, 61,744 elderlies and 9767 cases (15.81%) of hip fractures. In the lowest vs. highest categories of vitamin D in the elderly, pooled OR of hip fractures was 1.80 (95% CI 1.56-2.07, P ≤ 0.001), and modified OR was equal to 1.40 (95% CI 1.20-1.63 P ≤ 0.001). A subgroup analysis showed that the OR of a hip fracture was 2.16 (1.49-3.11, P ≤ 0.001) in case-control studies; 1.52 (1.29-1.79, P = 0.001) in cohort studies; and 1.41 (1.18-1.70, P ≤ 0.001) in case-cohort studies. CONCLUSION: Low serum vitamin D levels in the elderly are associated with an increase in the odds of hip fracture.