The Effects of Vitamin D Supplementation on C-Reactive Protein and Systolic and Diastolic Blood Pressure in Postmenopausal Women: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

BACKGROUND: An inverse relationship between vitamin D supplementation and C-reactive protein (CRP) and hypertension has been reported, mostly through observational data. This inverse relationship, however, has not been confirmed in randomized controlled trials (RCTs). A meta-analysis of RCTs is needed to provide more robust evidence. OBJECTIVE: This systematic review of RCTs was conducted to assess the effect of vitamin D supplementation on CRP, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in postmenopausal women. METHODS: Four databases (PubMed, Web of Science, Embase, and Scopus) were systemically searched to identify relevant RCTs published in international scientific journals up to January 2023. Changes from baseline and SDs of CRP, SBP, and DBP were compared between postmenopausal women who received vitamin D supplementation and those who did not (controls). These parameters were applied to compute the overall effect sizes using the random-effects model. Data were summarized as mean difference (MD) with 95% CI. Heterogeneity among arms was scrutinized using the Cochrane's Q test and I2 statistic. Publication bias was judged by means of funnel plots and Egger's test. RESULTS: Seven studies with 6 arms on CRP, 6 arms on SBP, and 6 arms on DBP were included in the meta-analysis. Combined effect sizes suggested a significant effect of vitamin D supplementation on CRP (MD = -0.65 mg/L; 95% CI -0.93 to -0.37 mg/L; P < .001). In addition, CRP concentrations were significantly reduced after vitamin D supplementation in studies with a duration of more than 3 months (MD = -0.91 mg/L; 95% CI -1.37 to -0.45 mg/L; P < .001) and studies involving doses of ≤1,000 IU/d (MD = -2.10 mg/L; 95% CI -2.51 to -1.68 mg/L; P < .001). Vitamin D supplementation did not reduce SBP significantly (MD = -1.06 mm Hg; 95% CI -2.43 to 0.30 mm Hg; P = .127) and DBP (MD = 0.003 mm Hg; 95% CI -0.86 to 0.86 mm Hg; P = .994) levels compared with control groups. CONCLUSIONS: This meta-analysis concluded that vitamin D supplementation is associated with reduced CRP concentrations among postmenopausal women.

The effect of a ketogenic diet on inflammation-related markers: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Despite the important role of inflammation-related factors on the occurrence of chronic diseases, there is still conflicting evidence about the effects of the ketogenic diet (KD) on these factors. OBJECTIVE: In order to obtain a better viewpoint, this study aimed to comprehensively investigate the effects of a KD on inflammation-related markers. DATA SOURCES: To find pertinent randomized controlled trials up to August 2023, databases including PubMed/Medline, Web of Science, Scopus, Cochrane Library, and Embase were searched. DATA EXTRACTION: This study included all randomized controlled trials investigating the effects of a KD on C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, and IL-10 levels. Pooled weighted mean difference (WMD) and 95% confidence intervals (CIs) were achieved by random-effects model analysis for the best estimation of outcomes. DATA ANALYSIS: Forty-four studies were included in this article. The pooled findings showed that a KD has an effect on lowering TNF-α (WMD: -0.32 pg/mL; 95% CI: -0.55, -0.09; P = 0.007) and IL-6 (WMD: -0.27 pg/mL; 95% CI: -0.52, -0.02; P = 0.036) compared with control groups. However, no significant effect was reported for others inflammation marker-related levels. The results of the subgroup analysis showed that, in trials following the KD for ≤8 weeks and in people aged ≤50 years, the reduction in TNF-α levels was significantly higher than in other groups. In addition, in people with a body mass index greater than 30 kg/m2 compared to a body mass index ≤30 kg/m2, IL-6 levels decreased to a greater extent after receiving the KD. CONCLUSIONS: Consequently, adherence to a KD appears to improve some markers associated with inflammation, including TNF-α and IL-6.

The effect of vitamin K supplementation on cardiovascular risk factors: a systematic review and meta-analysis.

Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is necessary because of the increased mortality risk of that. The aim of our meta-analysis is to reveal the general effect of vitamin K supplementation on its related risk factors. Original databases were searched using standard keywords to identify all randomized clinical trials (RCTs) investigating the effects of vitamin K on CVD. Pooled weighted mean difference (WMD) and 95 % confidence intervals (95 % CI) were achieved by random-model effect analysis for the best estimation of outcomes. The statistical heterogeneity was determined using the Cochran's Q test and I2 statistics. Seventeen studies were included in this systematic review and meta-analysis. The pooled findings showed that vitamin K supplementation can reduce homeostatic model assessment insulin resistance (HOMA-IR) (WMD: -0⋅24, 95 % CI: -0⋅49, -0⋅02, P = 0⋅047) significantly compared to the placebo group. However, no significant effect was observed on other outcomes. Subgroup analysis showed a significant effect of vitamin K2 supplementation compared to vitamin K1 supplementation on HOMA-IR. However, no significant effect was observed on other variables. Also, subgroup analysis showed no potential effect of vitamin K supplementation on any outcome and omitting any articles did not affect the final results. We demonstrated that supplementation with vitamin K has no effect on anthropometrics indexes, CRP, glucose metabolism, and lipid profile factors except HOMA-IR.

The effect of tibolone treatment on apolipoproteins and lipoprotein (a) concentrations in postmenopausal women: A meta-analysis of randomized controlled trials.

OBJECTIVE: Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic properties that is used as hormone replacement therapy (HRT) in postmenopausal women. Treatment with tibolone has been demonstrated to lead to changes of the lipid profile, including alterations in lipoprotein (a) and apolipoprotein levels. Hence, we conducted the present meta-analysis of randomized controlled trials (RCTs) to assess the effect of tibolone treatment on apolipoproteins and lipoprotein (a) values in postmenopausal women. METHODS: Several databases (Cochrane Library, PubMed/Medline, Scopus, and Google Scholar) were searched for English-language manuscripts published up to September 2023 that scrutinized the effects of tibolone administration on apolipoprotein A-I (ApoA-I), apolipoprotein A-II (ApoA-II), apolipoprotein B (ApoB), and lipoprotein (a) in postmenopausal women. The results were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI), generated using a random-effects model. RESULTS: Finally, 12 publications with 13 RCT arms were included in the current meta-analysis. The overall results from the random-effects model demonstrated a notable reduction in ApoA-I (n = 9 RCT arms, WMD: -34.96 mg/dL, 95 % CI: -42.44, -27.48, P < 0.001) and lipoprotein (a) (n = 12 RCT arms, WMD: -7.49 mg/dl, 95 % CI: -12.17, -2.81, P = 0.002) after tibolone administration in postmenopausal women. However, treatment with tibolone did not impact ApoA- II (n = 4 RCT arms, WMD: 1.32 mg/dL, 95 % CI: -4.39, 7.05, P = 0.64) and ApoB (n = 9 RCT arms, WMD: -2.68 mg/dL, 95 % CI: -20.98, 15.61, P = 0.77) values. In the subgroup analyses, we noticed a notable decrease in lipoprotein (a) levels when tibolone was prescribed to females aged < 60 years (WMD: -10.78 mg/dl) and when it was prescribed for ≤ 6 months (WMD: -15.69 mg/dl). CONCLUSION: The present meta-analysis of RCTs highlighted that treatment with tibolone reduces lipoprotein (a) and apolipoprotein A-I levels in postmenopausal women. As the decrease in serum lipids' concentrations is associated with a decrease in the risk of cardiovascular disease (CVD), treatment with tibolone could be a suitable therapy for postmenopausal women with elevated CVD risk.

The effects of bupropion alone and combined with naltrexone on blood pressure and CRP concentration: A systematic review and meta-regression analysis of randomized controlled trials.

BACKGROUND: Considering the conflicting effects of bupropion on parameters related to cardiovascular system including blood pressure and inflammation, in this meta-analysis study, we investigated the effects of this drug alone or in combination with naltrexone on systolic (SBP) and diastolic blood pressure (DBP) and C-reactive protein (CRP). METHODS: Scopus, PubMed/Medline, Web of Science and Embase databases were searched using standard keywords to identify all controlled trials investigating effects of bupropion alone and combined with naltrexone on the BP and CRP. Pooled weighted mean difference and 95% confidence intervals (CIs) were achieved by random-effects model analysis for the best estimation of outcomes. RESULTS: The pooled findings showed that that bupropion alone or in combination with naltrexone would significantly increase SBP (weighted mean difference (WMD): 1.34 mmHg, 95% CI: 0.38-2.29) and DBP (WMD: 0.93 mmHg, 95% CI 0.88-0.99) as well as decrease CRP (WMD: -0.89 mg/L, 95% CI -1.09 to -0.70). The findings of the subgroup also show the greater effect of bupropion on blood pressure (SBP and DBP) increase in a dose greater than 360 mg and a duration of intervention less equal to 26 weeks. In addition, the subgroup analysis showed that changes in SBP after receiving bupropion together with naltrexone were more compared to bupropion alone. CONCLUSIONS: The addition of combination therapies such as bupropion and naltrexone can significantly improve CRP levels. However, its effect on blood pressure requires proper management of this drug.

The impact of medroxyprogesterone acetate on lipid profiles in Women: A time and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: The effect of MPA on the lipid profile and CVD risk is still controversial; hence, this comprehensive dose-response meta-analysis of randomized controlled trials was conducted to assess the effect of MPA on lipid profiles in women. METHODS: A comprehensive search was conducted in the following databases: Web of Science, Scopus, PubMed/Medline, and Embase, up to October 20, 2023. A random-effects meta-analysis approach based on the DerSimonian and Laird method was used to compute the combined estimates of the intervention's impact on the lipid profile. RESULTS: 35 eligible studies with 58 arms were included in our meta-analyses analysis. Combined effect sizes suggested a significant effect of MPA on total cholesterol (TC) levels (WMD: -3.43 mg/dL, 95 % CI: -5.38 to -1.48, p < 0.001), HDL-C levels (WMD: -3.34 mg/dL, 95 % CI: -3.77 to -2.91, p < 0.001), and triglyceride (TG) levels (WMD: -9.13 mg/dL, 95 % CI: -10.92 to -7.33, p < 0.001). The subgroup meta-analysis revealed a more substantial reduction in TC in studies with dosages > 2.5 mg/day (WMD: -4.10 mg/dL), mean participant age lower than 60 years (WMD: -3.80 mg/dL), mean BMI lower than 25 kg/m2 (WMD: -5.61 mg/dL), duration of intervention of 12 months or more (WMD: -3.98 mg/dL), and when the baseline TC value was equal to or greater than 200 mg/dL (WMD: -4.13 mg/dL). CONCLUSIONS: The current meta-analysis showed a statistically significant decrease in TC, TG, and HDL-C levels and a non-significant increase in LDL-C levels after MPA administration in women.

The effect of metformin on adipokines levels: A systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND: Considering the role of adipokine on diseases related to metabolic syndrome and even chronic diseases, it seems necessary to investigate effective interventions on these factors. This study aimed to comprehensively investigate the effects of metformin on adipokines. METHODS: A comprehensive search was conducted in five databases using established keywords. The purpose of this search was to uncover controlled studies that have examined the impact of metformin on adipokines, specifically leptin, adiponectin, and resistin. The random-effects model analysis was used to provide pooled weighted mean difference and 95% confidence intervals. RESULTS: Forty-nine studies were included in this article. The pooled findings showed that that the administration of metformin significantly decreases leptin (WMD: -3.06 ng/ml, 95 % CI: -3.81, -2.30, P < 0.001) and resistin (WMD: -1.27 µg/mL, 95 % CI: -2.22, -0.31, P = 0.009) levels in different populations compared to the control group. However, no significant effect of this antidiabetic drug on adiponectin levels was reported. The results obtained from the subgroup results in the present study also showed that metformin in people with a BMI greater than 30 kg/m2 compared to a BMI ≤ 30 kg/m2 causes a significant decrease in leptin levels and an increase in adiponectin levels. Also, metformin in lower doses (≤1500 mg/day) and younger people (<30 years) causes a significant increase in adiponectin levels. CONCLUSIONS: In general, considering the role of adipokines on metabolic disease and even chronic disease, this drug can be used as a potentially useful drug, especially in obese people, to improve these factors.

The effect of subcutaneous dulaglutide on weight loss in patients with Type 2 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dulaglutide, a subcutaneously administered glucagon-like peptide 1 receptor agonist, has been hypothesized to lead to weight loss in patients with Type 2 diabetes mellitus (T2DM). However, the consequences of its prescription on body weight (BW) and other anthropometric indices, for example, body mass index (BMI) or waist circumference (WC), have not been completely clarified. Therefore, we aimed to assess the effects of subcutaneous dulaglutide administration on BW, BMI and WC values in T2DM subjects by means of a systematic review and meta-analysis of RCTs. METHODS: We computed a literature search in five databases (PubMed/Medline, Web of Science, EMBASE, Scopus and Google Scholar) from their inception to February 2023 to identify RCTs that examined the influence of subcutaneous dulaglutide on obesity indices. We calculated effect sizes using the random-effects model (using DerSimonian-Laird method). Results were derived across weighted mean differences (WMD) and 95% confidence intervals (CI). Subgroup analyses were applied to explore possible sources of heterogeneity among the RCTs. The current systematic review and meta-analysis was conducted in compliance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: In total, 18 studies with 33 RCT arms (BW = 33 RCT arms, 14,612 participants, 7869 cases and 6743 controls; BMI = 10 RCT arms, 14,612 subjects, 7869 cases and 6743 controls; WC = 10 RCT arms, 1632 participants, 945 cases and 687 cases) were included in the meta-analysis. BW (WMD: -0.86 kg, 95% CI: -1.22, -0.49, p < 0.001), BMI (WMD: -0.68 kg/m2 , 95% CI: -0.88, -0.49, p < 0.001) and WC (WMD: -1.23 cm, 95% CI: -1.82, -0.63, p < 0.001) values decreased notably following subcutaneous dulaglutide administration versus placebo. BW notably decreased in RCTs lasting >18 weeks (WMD: -1.42 kg, 95% CI: -1.90, -0.94, p < 0.001), whereas notable reductions in WC were seen in RCTs lasting ≤18 weeks (WMD: -1.78 cm, 95% CI: -2.59, -0.98, p < 0.001). Dulaglutide dosages >1 mg/day significantly decreased BW (WMD: -1.94 kg, 95% CI: -2.54, -1.34, p < 0.001), BMI (WMD: -0.80 kg/m2 , 95% CI: -1.07, -0.54, p < 0.001) and WC (WMD: -1.47 cm, 95% CI: -1.80, -1.13, p < 0.001). BW decreased particularly following dulaglutide prescription in individuals with obesity (WMD: -1.05 kg, 95% CI: -1.28, -0.82, p < 0.001) versus overweight. The dose-response meta-analysis revealed that BW decreased significantly when dulaglutide was prescribed in doses ≤3 mg/day versus >3 mg/day. CONCLUSIONS: Subcutaneous dulaglutide administration in T2DM reduces BW, BMI and WC. The decrease in BW and WC was influenced by the dose and the duration of dulaglutide administration. The reduction in BMI was only influenced by the dosage of dulaglutide. Moreover, T2DM patients who suffered from obesity experienced a notable decrease in BW versus T2DM subjects without obesity.

Changes in lipid profile and glucose metabolism following administration of bupropion alone or in combination with naltrexone: A systematic review and meta-regression analysis.

BACKGROUND: Considering the conflicting effects of bupropion on parameters related to metabolic syndrome including glucose metabolism and lipid profile, in this meta-analysis study, we investigated the effects of this drug alone or in combination with naltrexone on glucose metabolism and lipid profile. METHODS: Scopus, PubMed/Medline, Web of Science and Embase databases were searched using standard keywords to identify all controlled trials investigating effects of bupropion alone and combined with naltrexone on the glucose and lipid profile. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model. RESULTS: Twelve studies with 5152 participants' were included in this article. The pooled findings showed that bupropion alone or in combination with naltrexone would significantly reduce glucose (weighted mean difference (WMD): -2.25 mg/dL, 95% confidence interval (CI): -4.10, -0.40), insulin (WMD: -4.06 µU/mL, 95% CI: -6.09, -2.03), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.58, 95% CI: -0.98, -0.19), triglyceride (TG) (WMD: -11.78 mg/dL, 95% CI: -14.48 to -9.08) and increase high-density lipoprotein (HDL) (WMD: 2.68 mg/dL, 95% CI: 2.13 to 3.24). A Greater reduction in glucose levels was observed with duration >26 weeks. Dose of bupropion intake ≤360 mg and intervention for more than 26 weeks decreased insulin level significantly. With regard to lipid profile, reduction of triglycerides is more significant with dose of bupropion greater than 360 mg and a shorter intervention length equal to 26 weeks. CONCLUSIONS: The addition of combination therapies such as bupropion and naltrexone to lifestyle modification can significantly improve glucose metabolism and some lipid parameters.

Impact of Gluten-free Diet on Anthropometric Indicators in Individuals With and Without Celiac Disease: A Systematic Review and Meta-analysis.

PURPOSE: Previous studies have found that a gluten-free diet (GFD) may have improve obesity-related factors. For this reason, we conducted a systematic review and meta-analysis to investigate the effect of a GFD on anthropometric indicators. METHODS: We performed a systematic search in databases from inception until July 12, 2022. We included all relevant articles that evaluate efficacy of a GFD on anthropometric indicators in patients with and without celiac disease (CD). Random-effects models were applied to combine the data. The main outcomes were then analyzed using weight mean differences (WMDs) and 95% CIs. FINDINGS: A total of 27 articles met the eligible criteria and were included. Pooled results from the random-effects model indicated that the GFD has no significant effect on any of the factors of anthropometry, including weight (WMD, 1.20 kg; 95% CI, -1.16 to 3.55 kg; P = 0.319), body mass index (WMD, 0.70 kg/m2; 95% CI, -0.45 to 1.84 kg/m2; P = 0.233), waist circumference (WMD, 0.92 cm; 95% CI, -1.34 to 3.17 cm; P = 0.497), and body fat (WMD, 1.02%; 95% CI, -0.38% to 2.42%; P = 0.153). The subgroup results indicated that after implementation of a GFD significant increased weight and body fat occurred in patients with compared with without CD. In addition, the effect of this diet on the increase of BMI and body fat in the intervention of more than 48 weeks was significantly higher. IMPLICATIONS: The results of the present study indicate that a GFD can have a significant and beneficial effect on weight and body fat in patients with CD.

In-vitro Antioxidant, In-vitro and In-silico Ovarian Anticancer Activity (Ovarian Cancer Cells-PA1) and Phytochemical Analysis of Cissus quadrangularis L. Ethanolic Extract.

BACKGROUND: Cissus quadrangularis is a valuable natural source of traditional medicines. OBJECTIVE: An in vitro investigation was performed to determine whether the ethanolic extract from the whole portions of C. quadrangularis had anticancer and free radical scavenging activities against ovarian cancer cells-PA1. C. quadrangularis is a herb collected from rural areas in Andhra Pradesh, India. MATERIALS AND METHODS: C. quadrangularis was air-dried and crushed, and the powder and ethanol (0.5 kg) were used in a Soxhlet device for continuous extraction. Phytochemical analysis of the extracts was performed using a standard procedure. The antioxidant activity of the ethanolic extract of C. quadrangularis was evaluated using DPPH. An in vitro anticancer study used an ethanolic extract against the PA1 cell line. Apoptosis of ovarian cancer cells was studied using DAPI and carboxy-H2DCFDA staining. From LC-MS analysis, quercetin-3-O-alpha-Lrhamnopyranoside and erucic acid were docked with the threonine tyrosine kinase (TTK) enzyme using auto docking. RESULTS: The ethanolic extract of C. quadrangularis demonstrated significant dose-dependent antioxidant activity compared to ascorbic acid. The ethanolic extract of C. quadrangularis was found to have high anticancer activity against ovarian cancer cell lines (PA1), with an IC50 value of 482.057 ± 113.857 µg/ml. DAPI and carboxy-H2DCFDA staining confirmed that C. quadrangularis ethanolic extract induced apoptosis in ovarian cancer cells (p < .001). Molecular docking studies helped identify the binding affinities between the protein and ligand complexes, such as Quercetin-3-O-alpha-Lrhamnopyranoside binding sites of target proteins 5N7V (MET602, GLN672) and erucic acid 5N7V (GLY354). Quercetin-3-O-alpha-L-rhamnopyranoside was reported to bind with 5N7V by hydrogen bonding at MET602 and GLN672 amino acids with 2.02, 2.99 Å bonding length distance and binding affinity of -7.9 kcal/mol. Erucic acid was reported to bind with 5N7V by hydrogen bonding at GLY354 amino acid with 3.18, 2.93 Å bonding length (Å) distance and binding affinity of -4.3 kcal/mol. The current analysis showed that the ethanolic extracts of C. quadrangularis L. exhibited antioxidant and anticancer properties against ovarian PA1 cells. CONCLUSION: The experimental results confirmed that C. quadrangularis L. is a promising, safe chemotherapeutic plant for ovarian cancer PA1 cells. The docking results demonstrated that Quercetin-3-O-alpha-L-rhamnopyranoside strongly binds threonine tyrosine kinase at the MET602 and GLN672 positions. This study showed that the C. quadrangularis ethanolic extract has Quercetin-3-O-alpha-L-rhamnopyranoside, which can be used as an anticancer agent.

Betanin inhibits PI3K/AKT/mTOR/S6 signaling pathway, cell growth and death in osteosarcoma MG-63 cells.

It is possible to develop new chemopreventive compounds so that cancer cells can be targeted in an exclusive manner. Bioactive natural compounds have demonstrated to be efficient chemotherapeutic agents, safe and cost-effective. Majority of anti-cancer medications are derived from natural sources, particularly of plant origins. Betanin (betanidin-5-O-ß-glucoside) is the most common betacyanin with antioxidant, anti inflammatory and anticancer properties. The present study therefore investigated the effect of betanin onosteosarcoma MG-63 cells. The mechanistic pathway of inflammatory responses, cell proliferation and apoptosis were investigated. The MG-63 cells were treated with betanin for 24 h. Betanin actions on the appearance of cell arrangements, morphological changes, ROS induced Δψm , cell migration, cell adhesion and proliferative mechanistic marker expression of PI3K/AKT/mTOR/S6were analyzed. Betanin inhibited MG-63 cells at IC50 concentrations between 9.08 and 54.49 µM and induced apoptosis by triggering the ROS mechanism. Betanin inhibited proliferation and migration of MG-63 cells and induced DNA fragmentation. Betanin also modified the key mediator expression levels of PI3K/AKT/mTOR/S6 signaling pathways. Betanin can potentially be utilized in bone carcinoma therapeutics to inhibit, reverse or delay osteosarcoma.

The effect of 17beta-estradiol plus norethisterone acetate on anthropometric indices: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Little evidence exists on the effect of 17beta-estradiol plus norethisterone acetate on all the anthropometric indices. Hence, this systematic review and meta-analysis of Randomized Controlled Trials was conducted to give an evidence-based report on the effect of 17beta-estradiol plus norethisterone acetate on anthropometric indices. METHODS: The literature search was executed in databases including PubMed/Medline, Web of Science, Scopus, Embase, and Google Scholar to recognize clinical trials that examined the influence of 17beta-estradiol plus norethisterone acetate on obesity indices from database inception to Jan 2023. RESULTS: Combined findings were generated from 20 eligible articles. The meta-analysis showed that body weight (Weighted Mean Difference (WMD): -0.47 kg, 95% CI: -1.32, 0.37, p = 0.274), body fat (WMD: 0.16 kg, 95% CI: -1.26, 1.59, p = 0.821), WHR (WMD: 0.001 kg, 95% CI: -0.006, 1.15, p = 0.872), and LBM (WMD: -0.02 kg, 95% CI: -1.19, 1.15, p = 0.970) were not modified in DHEA group compared to the control, but BMI levels were significantly reduced in 17beta-estradiol plus norethisterone acetate group (WMD: -0.15 kg/m2, 95% CI: -0.30, -0.008, p = 0.039). Moreover, based on intervention duration (months), a more significant reduction in BMI was found in trials that were performed on studies with ˃3 months duration (WMD: -0.176 kg/m2) than studies with ≤ 3 months (WMD: 0.05 kg/m2). CONCLUSION: Administration of 17beta-estradiol plus norethisterone acetate for more than 3 months results in a decrease in BMI, which helps to reduce cardiovascular disease risk.

The effect of green tea supplementation on the anthropometric outcomes in overweight and obese women: a time and dose-response meta-analysis of randomized controlled trials.

Inconsistencies are evident within the literature regarding the role of Green Tea (GT) supplementation on women living with obesity. To address this, we conducted to determine the impact of GT supplementation on the weight, body mass index (BMI), and waist circumference (WC) in overweight and obese women using time and dose-response meta-analysis of randomized controlled trials (RCTs). This meta-analysis searched electronic Scopus, Web of Science, Embase, and PubMed/Medline databases from inception to December 1st, 2022. Data were reported as weighted mean difference (WMD) with 95% confidence interval (CI). A total of 2061 references were identified, and 15 articles with 16 RCT arms on body weight, 17 RCT arms on BMI, and 7 RCT arms on WC were included in the meta-analysis. GT supplementation significantly decreases body weight (WMD: -1.23 kg, 95% CI: -2.13 to -0.33, p = 0.007), BMI (WMD: -0.47 kg/m2, 95% CI: -0.87 to -0.07, p = 0.020) and WC (WMD: -3.46 cm, 95% CI: -6.75 to -0.16, p = 0.040). In subgroup analyses, GT consumption demonstrated lowered body weight with dosaes ≥1000 mg/day (WMD: -1.38 kg), in the RCTs, which lasted ≥8 wk (WMD: -1.24 kg). The non-linear dose-response assessment detected a negative correlation between the changes in body weight and BMI in green tea consumption of more than 1000 (mg/day). The GT supplementation reduced the weight, BMI, and WC in overweight and obese women. In clinical practice, healthcare professionals can recommend using GT with dosages ≥ 1000mg/day and duration ≥ 8 wk in obese women.

Whole genome analysis and homology modeling of SARS-CoV-2 Indian isolate reveals potent FDA approved drug choice for treating COVID-19.

Coronaviruses have caused enough devastation in the last two decades. These viruses have some rare features while sharing some common features. Novel coronavirus disease (nCoV-19) caused an outbreak with a fatality rate of 5%. It emerged from China and spread into many countries. The present research focused on genome analysis of Indian nCoV-19 Isolate and its translational product subjected to homology modeling and its subsequent molecular simulations to find out potent FDA approved drug for treating COVID-19. Phylogenetic analysis of SARS-CoV-2 Indian isolate shows close resemblance with 17 countries SARS-CoV-2 isolates. Homology modeling of four non-structural proteins translational product of Indian SARS-CoV-2 genome shows high similarity and allowed regions with the existing PDB deposited SARS-CoV-2 target proteins. Finally, these four generated proteins show more affinity with cobicistat, remdesivir and indinavir out of 14 screened FDA approved drugs in molecular docking which is further proven by molecular dynamics simulation and MMGBSA analysis of target ligand complex with best simulation trajectories. Overall our present research findings is that three proposed drugs namely cobicistat, remdesivir and indinavir showed higher interaction with the model SARS-CoV-2 viral target proteins from the Indian nCoV-19 isolate. These compounds could be used as a starting point for the creation of active antiviral drugs to combat the deadly COVID-19 virus during global pandemic and its subsequent viral infection waves across the globe.Communicated by Ramaswamy H. Sarma.

Nerolidol induced apoptosis via PI3K/JNK regulation through cell cycle arrest in MG-63 osteosarcoma cells.

The aim of the present study was to determine the cell proliferation, apoptotic pathway analysis through protein, mRNA and cell cycle arrest mechanism in nerolidol induced osteosarcoma MG-63 cells. The osteosarcoma MG-63 cells were treated with various doses of nerolidol (15 and 20 µM/ml) for 24 h. Cell proliferation was examined using assist method of MTT assay, fixed the IC50 value of nerolidol 15 µM/ml. Reactive oxygen species (ROS) generation was analyzed by DCFH-DA dye, mitochondrial potential detected by Rh-123 dye, apoptotic morphological changes identified by AO/EtBr, PI, DAPI staining, and cell adhesion were detected by using fluorescence microscope. Cell proliferation, and apoptotic molecular protein and mRNA expressions such as ERK, P38, p-PI3K, p-JNK, Bcl-2, JNK, p-P38, cyclin-D1, and Bax were analyzed in osteosarcoma MG-63 cells. Nerolidol significantly suppressed the osteosarcoma cells progression in a dose dependent manner (p < .05) evident in the oxidative stress induction and apoptotic morphological changes. Nerolidol also regulated the protein PI3K/AKT mechanistically via induction of apoptosis Nerolidol suppresses osteosarcoma MG-63 cells by PI3K/AKT by cell cycle arrest at early phase of G0/G1. To sum up, nerolidol suppressed the growth of bone cancer cells and can be finally targeted as a potent drug for analyzing its chemotherapeutic effects in future.

Corilagin induces apoptosis and inhibits HMBG1/PI3K/AKT signaling pathways in a rat model of gastric carcinogenesis induced by methylnitronitrosoguanidine.

Gastric cancer, invasive cancer of the gastrointestinal tract, found in developing countries. Chemotherapy to patients with advanced gastric cancer, exhibits greater drug resistance to standard chemotherapy drugs. Therefore, important to establish anti-cancer drugs that are successful for cancer therapy. Corilagin is a natural ellagitannin (ET) with profound pharmacological properties has been used for the study to assess its anticancer effects against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) stimulated gastric cancer rats. Biochemical studies showed Thiobarbituric acid reactive substances (TBARS) and enzymatic and non-enzymatic antioxidants increased in corilagin treated animals compared with controls. Histopathologic evaluation revealed corilagin treated rats showed cell morphology similar that control showing its ameliorating effects. In corillagen treament mRNA protein expression levels of HIF-1α, AKT, PI3K, CT4, CD147 and HMGB1 were drastically lowered transcription factors triggering gastric cancer. In Western blot analysis showed released higher apoptotic marker of caspase-3, -9, Bax while Bcl-2 levels were significantly reduced confirming that corilagin triggers apoptosis in gastric cancer.

Effects of Syringic Acid on Apoptosis, Inflammation, and AKT/mTOR Signaling Pathway in Gastric Cancer Cells.

Gastric cancer is one of the most common cancer and deadly disease worldwide. Despite substantial advances made in the treatment of gastric cancer, existing therapies still encounter bottlenecks. Chemotherapy, for instance, could lead to serious side effects, high drug resistance and treatment failure. Phytochemical-derived compounds from plants offer novel strategies as potent drug molecules in cancer therapy. Given the low toxicity and higher tolerance rate of naturally occurring compounds, the present study evaluated the effects of syringic acid on cytotoxicity, oxidative stress, mitochondrial membrane potential, apoptosis, and inflammatory responses in gastric cancer cell line (AGS). AGS cells were treated with various concentrations (5-40 µg/mL) of syringic acid for 24 h, after which cytotoxicity was analyzed. Reactive Oxygen Species (ROS), antioxidant enzyme activities, mitochondrial membrane potential (MMP, Δψ m), cell morphologies, the expression of apoptotic markers and protein expression patterns were also investigated. Results indicated that syringic acid-treated cells developed anti-cancer activities by losing MMP, cell viability, and enhancing intracellular ROS. Syringic acid selectively developed apoptosis in a dose-dependent manner via enhanced regulation of caspase-3, caspase-9 and Poly ADP-ribose Polymerase (PARP) whereas decreasing the expression levels of p53 and BCL-2. Syringic acid also lowered activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) whereas Thio Barbituric Acid Reactive Substances (TBARS) increased. Syringic acid suppressed gastric cancer cell proliferation, inflammation, and induced apoptosis by upregulating mTOR via AKT signaling pathway. The study suggests syringic acid may constitute a promising chemotherapeutic candidate for gastric cancer treatment. Our study is the first report on the anti-cancer effects of syringic acid against gastric cancer cells via apoptosis, inhibition of inflammation, and the suppression of the mTOR/AKT signaling pathway.

Inhibiting the PI3K/Akt, NF-κB signalling pathways with syringic acid for attenuating the development of oral squamous cell carcinoma cells SCC131.

OBJECTIVES: To evaluate the anti-inflammatory and antiproliferative effect of syringic acid (SRA) on oral squamous cell carcinoma (OSCC) SCC131 cells via suppression of NF-κB-induced PI3K/Akt signalling pathway. METHODS: The present study assesses the anticancer effects of SRA alongside human oral cancer (HOC) SCC131 cells through the fabrication of reactive oxygen species (ROS) and activated apoptosis. DAPI and Rh-123 staining were used to assess the apoptotic nuclear characteristic, mitochondrial membrane potential, cell adhesion and migration by fluorescence microscope with SRA treatment. KEY FINDINGS: Syringic acid inhibits cell viability (IC50 values of 25 µm), adhesion, migration and induced apoptosis. MTT assay demonstrated SRA-induced apoptotic events, inhibition of invasion and angiogenic signalling in SCC131 cell line. Furthermore, SRA treated with SCC131 cells suppresses the protein expression of inflammatory, angiogenesis and PI3K/Akt signalling pathways. It is suggested that SRA prevents the translocation of NF-κB and PI3K/Akt activated products to the nucleus, thereby suppressing angiogenesis via downregulation of vascular endothelial growth factor. CONCLUSIONS: Therefore, addition of SRA to SCC131 cells may provide a promising natural therapeutic strategy against squamous cell carcinomas with potential application in clinical analysis.