Coffee consumption and caffeine intake in relation to risk of fractures: a systematic review and dose-response meta-analysis of observational studies.

BACKGROUND: Conflicting reports are available about the association of coffee or caffeine intake and risk of fracture. We performed the current updated systematic review and dose-response meta-analysis of coffee consumption and caffeine intake and risk of fracture to quantify this association. MATERIALS AND METHODS: PubMed/Medline, ISI Web of Science, and Scopus, Cochrane database were searched up to July 2021. Random-effects model or fixed-effects model was used to pool the study-specific effect sizes (ESs) and 95% confidence intervals (CIs). Dose-response relationship was examined using linear and non-linear dose-response analyses. The certainty of evidence was assessed using NutriGrade tool. RESULTS: Out of 22 eligible studies included in the meta-analysis, 15 had cohort and 7 had case-control design. We found no significant association between coffee consumption and risk of fracture, either based on pooling cohort (RR: 0.99; 95% CI: 0.88, 1.12; I2 = 71.4%, Pheterogeneity < 0.01) or case-control studies (OR: 1.13; 95% CI: 0.87, 1.46; I2 = 49.0%, Pheterogeneity=0.08). In the subgroup analysis of cohort studies, we observed that higher coffee intake was inversely associated with risk of fracture in men (RR: 0.85; 95% CI: 0.76 to 0.94). In addition, a positive association was seen between coffee consumption and risk of fracture in studies with less than 12 years of follow-up (RR: 1.14; 95% CI: 1.02 to 1.27). With regard to caffeine intake, a statistically significant positive association was seen with risk of fracture (RR: 1.15; 95% CI, 1.08 to 1.23; I2=26.6%, n = 8). In the dose-response analysis, we found that each additional 100 mg caffeine intake was marginally associated with 2% greater risk of fracture (RR: 1.02; 95% CI: 1 to 1.05; I2= 70.3%, n = 6). CONCLUSION: High coffee consumption was protectively associated with risk of fracture in men, while caffeine intake was positive associated with risk.

Application of plant-derived exosome-like nanoparticles in drug delivery.

Exosomes are one type of extracellular vesicles with size ranging from 30 to 150 nm, which are involved in intercellular communication by transporting specific proteins, nucleic acids, and low molecular weight metabolites. The size and competence of exosomes to transfer biological materials to recipient cells have made them suitable for biomedical use. Therefore, exosomes have been studied as drug delivery systems for various diseases due to low immunogenicity, preferred tumor homing, innate and acquired targetability, and stability. They are secreted by almost all cells from multivesicular endosomes and retrieved in all body fluids including bile, saliva, blood, lymph, urine, cerebrospinal fluid, milk, and etc. Plants' organs also secrete exosomes (Plant-derived exosome-like nanoparticles (PELNs)) which have been considered as an economical and affordable source of production. PELNs are pharmacologically rich in active molecules because of owning unique compositional and morphological features and they can be used as natural nano-carrier for transporting exogenous molecules. In this review, the bio-component and the applications of PELNs as drug delivery systems in neural disorders, tumor-targeted delivery, and gene delivery have been reviewed in different plants such as aloe, turmeric, ginger, lemon, grapefruit, grape, and strawberry.

Fabrication and characterization of lipopeptide biosurfactant-based electrospun nanofibers for use in tissue engineering.

Nanofibers are a class of nanomaterial with specific physicochemical properties and characteristics making them quite sought after and investigated by researchers. Lipopeptide biosurfactant (LPB) formulation properties were previously established in wound healing. LPB were isolated from in vitro culture of Acinetobacter junii B6 and loaded on nanofibers formulation produced by electrospinning method with different ratios of carboxymethylcellulose (CMC), polyvinyl alcohol (PVA), and Poloxamer. Numerous experimental control tests were carried out on formulations, including physicochemical properties which were evaluated by using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), morphology study by scanning electron microscopy (SEM), and thermal stability. The best nanofibers formulation was obtained by the electrospinning method, with a voltage of 19.8 volts, a discharge capacity of 1cm/h, a cylindrical rotating velocity of 100rpm, and a needle interval of 7cm from the cylinder, which continued for 7hours. The formulation contained 2% (w/v) CMC, 10% (w/v) poloxamer, 9% (w/v) PVA, and 5% (w/v) LPB. This formula had desirable physicochemical properties including spreadability, stability, and uniformity with the particle size of about 590nm.

The effects of Anethum graveolens (dill) supplementation on lipid profile and glycemic control: a systematic review and meta-analysis of randomized controlled trials.

There is an increased interest in the potential health benefits of nutraceutical therapies, such as Anethum graveolens (dill). Therefore, this systematic review and meta-analysis aimed to evaluate the effects of Anethum graveolens supplementation on lipid profiles and glycemic indices in adults. A systematic search was performed for literature published through November 2020 via PubMed/Medline, Scopus, ISI Web of Science, and Embase to find randomized controlled trials (RCTs) evaluating the effects of oral supplementation with A. graveolens on lipid profile and measures of glycemic control in adults. The random-effects model was applied to establish the weighted mean difference (WMD) and associated 95% confidence intervals (CI). Seven RCTs with a total number of 330 subjects were included in the final analysis. Pooled results indicated that A. graveolens supplementation significantly decreased low-density lipoprotein cholesterol (LDL) concentration (WMD: -15.64 mg/dL; 95% CI: -24.55 to -6.73; P = 0.001), serum insulin (WMD: -2.28 µU/ml; 95% CI: -3.62 to -0.93; P = 0.001), and HOMA-IR (WMD: -1.06; 95% CI: -1.91 to -0.20; P = 0.01). However, there was no significant effect on serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and fasting blood glucose (FBS). Subgroup analysis suggested that using A. graveolens in higher doses and long-term duration had beneficial effects on lipid profiles. Dose-response analysis also showed a significant reduction in FBS at doses of 1500 mg/d. The present meta-analysis indicated that Anethum graveolens could exert favorable effects on insulin resistance and serum LDL. Further research is necessary to confirm our findings.

Association between dietary inflammatory index scores and the increased disease activity of rheumatoid arthritis: a cross-sectional study.

BACKGROUND: Diet plays an important role in regulating inflammation, which is a hallmark of rheumatoid arthritis (RA). Our aim was to investigate the association between the Dietary Inflammatory Index (DII) scores and RA activity. METHODS: This cross-sectional study was conducted on 184 patients with RA in rheumatology clinic in Kermanshah city, Iran, in 2020. RA was diagnosed according to the criteria of the 2010 American College of Rheumatology/ European League against Rheumatism. The overall inflammatory potential of the diet was extracted from a validated 168-item food frequency questioner (FFQ) using the DII. RA disease activity was assessed using Disease Activity Score 28 (DAS-28) scores. Logistic regression and one-way ANOVA/ ANCOVA were conducted. RESULTS: Individuals in the highest DII quartile had the significantly higher odds of positive C-reactive protein than those in the lowest quartile of the DII scores (OR 4.5, 95% CI 1.16 - 17.41, P = 0.029). A statistically significant downward linear trend in fat-free mass and weight were observed with increasing the DII quartiles (P = 0.003, P = 0.019, respectively). Patients in the highest DII quartile had higher DAS-28 scores than those in the first quartile (Mean difference: 1.16, 95% CI 0.51 - 1.81, P < 0.001) and second quartile of the DII scores (Mean difference: 1.0, 95% CI 0.34 - 1.65, P < 0.001). CONCLUSION: Our results indicated that reducing inflammation through diet might be one of the therapeutic strategies to control and reduce the disease activity in RA patients.

Nutritional status of under six years old children in Kalar city, Kurdistan Region, Iraq.

INTRODUCTION: Nutritional problems in children cause major morbidity and mortality in the world. This study aimed to assess the nutritional status of under six years old children in Kalar city, Kurdistan Region, Iraq. METHODS: In this longitudinal study, data from 403 Iraqi Kurdish children aged 0-72 months and their mothers were extracted from Health Centre in Kalar city undertaken between 2013 and 2019. The children`s growth data were obtained at birth time, 6, 12, 24, and 72 months. Epi Info was used to classify the children of nutritional status by converting the anthropometric measurements into Z-scores. Data were analyzed using SPSS 25 software. RESULTS: The prevalence of overweight and obesity rose from birth to age 6 years old, from 19.6% and 7.4% to 52.2% and 30.5%, respectively. At 24 month, children had the highest rates of being overweight (56.1%) and obesity (34%). At 6 month, the highest prevalence of wasting exists (9.5%). At 6 month boys and girls had the highest frequency of stunting, 17.2% and 7.2% respectively. Considering the association of all characteristic variables and growth data at birth time, only mothers with academic education had children with significantly higher BMI for age compared to illiterate mothers after adjusting for all potential confounders (ß: 0.573, 95% CI: 0.105, 1.04, P: 0.017). CONCLUSION: The study suggests that some analysed factors that accounted for malnutrition in Kalar city's children are preventable. Therefore, to reduce the burden of malnutrition, community-based education and targeted nutritional interventions are required.

The association between food insecurity and gestational weight gain: A systematic review and meta-analysis.

Gestational weight gain has been one of the most important risk factors for adverse maternal, perinatal, and long-term outcomes. Our systematic review and meta-analysis aimed to incorporate the evidence regarding the association between gestational weight gain and food insecurity (FI). We performed a systematic review and meta-analysis on the possible association between FI and insufficient or excessive gestational weight gain by conducting a systematic search in PubMed, Scopus, ISI, and Google Scholar from January 1, 1990 until February 1, 2022. Odds Ratio (OR) was pooled using a random-effects model. Standard methods were used for the assessment of heterogeneity and publication bias. Data included fifteen studies with 7651 individual participants from different countries pooled for the meta-analysis. Of the fifteen studies included in the final meta-analysis, seven had a cross-sectional and eight had a longitudinal design. In the pooled analysis, FI had significant relationship with both inadequate (OR = 1.49; 95% CI = 1.26 to 1.76) and excessive weight gain in pregnancy (OR = 1.27; 95% CI = 1.05 to 1.54). In conclusion, FI during pregnancy was directly associated with both inadequate and excessive gestational weight gain. Therefore, changes at a policy level should be considered to increase food security in pregnant women.

Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials.

Clinical trial studies revealed conflicting results on the effect of Ashwagandha extract on anxiety and stress. Therefore, we aimed to evaluate the effect of Ashwagandha supplementation on anxiety as well as stress. A systematic search was performed in PubMed/Medline, Scopus, and Google Scholar from inception until December 2021. We included randomized clinical trials (RCTs) that investigate the effect of Ashwagandha extract on anxiety and stress. The overall effect size was pooled by random-effects model and the standardized mean difference (SMD) and 95% confidence interval (CIs) for outcomes were applied. Overall, 12 eligible papers with a total sample size of 1,002 participants and age range between 25 and 48 years were included in the current systematic review and meta-analysis. We found that Ashwagandha supplementation significantly reduced anxiety (SMD: -1.55, 95% CI: -2.37, -0.74; p = .005; I2  = 93.8%) and stress level (SMD: -1.75; 95% CI: -2.29, -1.22; p = .005; I2  = 83.1%) compared to the placebo. Additionally, the non-linear dose-response analysis indicated a favorable effect of Ashwagandha supplementation on anxiety until 12,000 mg/d and stress at dose of 300-600 mg/d. Finally, we identified that the certainty of the evidence was low for both outcomes. The current systematic review and dose-response meta-analysis of RCTs revealed a beneficial effect in both stress and anxiety following Ashwagandha supplementation. However, further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

Smart-Home Concept for Remote Monitoring of Instrumental Activities of Daily Living (IADL) in Older Adults with Cognitive Impairment: A Proof of Concept and Feasibility Study.

Assessment of instrumental activities of daily living (IADL) is essential for the diagnosis and staging of dementia. However, current IADL assessments are subjective and cannot be administered remotely. We proposed a smart-home design, called IADLSys, for remote monitoring of IADL. IADLSys consists of three major components: (1) wireless physical tags (pTAG) attached to objects of interest, (2) a pendant-sensor to monitor physical activities and detect interaction with pTAGs, and (3) an interactive tablet as a gateway to transfer data to a secured cloud. Four studies, including an exploratory clinical study with five older adults with clinically confirmed cognitive impairment, who used IADLSys for 24 h/7 days, were performed to confirm IADLSys feasibility, acceptability, adherence, and validity of detecting IADLs of interest and physical activity. Exploratory tests in two cases with severe and mild cognitive impairment, respectively, revealed that a case with severe cognitive impairment either overestimated or underestimated the frequency of performed IADLs, whereas self-reporting and objective IADL were comparable for the case with mild cognitive impairment. This feasibility and acceptability study may pave the way to implement the smart-home concept to remotely monitor IADL, which in turn may assist in providing personalized support to people with cognitive impairment, while tracking the decline in both physical and cognitive function.

What is the influence of cinnamon supplementation on liver enzymes? A systematic review and meta-analysis of randomized controlled trials.

Existing evidence has uncovered the potential health benefits of cinnamon intake; however, its effect on liver function is unclear. Thus, the aim of this systematic review and meta-analysis was to examine the effect of cinnamon supplementation on liver enzymes. Relevant articles were identified through a systematic search in PubMed/Medline, Scopus, Web of Science, Cochrane Library, and Embase up to September 2020. All trials assessing the effect of oral cinnamon supplementation on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in adults were included. The pooled effect sizes were obtained using the random-effects model and expressed as mean difference (MD) and 95% confidence intervals (CI). A total of seven original trials (nine treatment arms) involving a total of 256 subjects were included in the final analysis. The pooled analysis indicated that cinnamon supplementation had no significant effect on serum levels of ALT, AST, and ALP. However, there was a significant reduction in ALT levels in patients with type 2 diabetes (MD: -4.01 U/L; 95% CI: -6.86, -1.15) and in trials with low-dose supplementation (<1,500 mg/d), follow-up duration longer than 12 weeks, and in the elderly patients (aged>50 years). The beneficial effects of cinnamon intake were also shown in AST levels in patients with type 2 diabetes and trials with long-term follow-up (>12 weeks). Longer-term, oral cinnamon supplementation may improve serum levels of liver enzymes in patients with type 2 diabetes. Further high-quality studies are needed, especially in populations with abnormal liver enzyme levels, to firmly establish the clinical efficacy of cinnamon on liver function.

Enhancement of BDNF Expression and Memory by HDAC Inhibition Requires BET Bromodomain Reader Proteins.

Histone deacetylase (HDAC) inhibitors may have therapeutic utility in multiple neurological and psychiatric disorders, but the underlying mechanisms remain unclear. Here, we identify BRD4, a BET bromodomain reader of acetyl-lysine histones, as an essential component involved in potentiated expression of brain-derived neurotrophic factor (BDNF) and memory following HDAC inhibition. In in vitro studies, we reveal that pharmacological inhibition of BRD4 reversed the increase in BDNF mRNA induced by the class I/IIb HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Knock-down of HDAC2 and HDAC3, but not other HDACs, increased BDNF mRNA expression, whereas knock-down of BRD4 blocked these effects. Using dCas9-BRD4, locus-specific targeting of BRD4 to the BDNF promoter increased BDNF mRNA. In additional studies, RGFP966, a pharmacological inhibitor of HDAC3, elevated BDNF expression and BRD4 binding to the BDNF promoter, effects that were abrogated by JQ1 (an inhibitor of BRD4). Examining known epigenetic targets of BRD4 and HDAC3, we show that H4K5ac and H4K8ac modifications and H4K5ac enrichment at the BDNF promoter were elevated following RGFP966 treatment. In electrophysiological studies, JQ1 reversed RGFP966-induced enhancement of LTP in hippocampal slice preparations. Last, in behavioral studies, RGFP966 increased subthreshold novel object recognition memory and cocaine place preference in male C57BL/6 mice, effects that were reversed by cotreatment with JQ1. Together, these data reveal that BRD4 plays a key role in HDAC3 inhibitor-induced potentiation of BDNF expression, neuroplasticity, and memory.SIGNIFICANCE STATEMENT Some histone deacetylase (HDAC) inhibitors are known to have neuroprotective and cognition-enhancing properties, but the underlying mechanisms have yet to be fully elucidated. In the current study, we reveal that BRD4, an epigenetic reader of histone acetylation marks, is necessary for enhancing brain-derived neurotrophic factor (BDNF) expression and improved memory following HDAC inhibition. Therefore, by identifying novel epigenetic regulators of BDNF expression, these data may lead to new therapeutic targets for the treatment of neuropsychiatric disorders.

Inflammatory potential of the diet and risk of sarcopenia and its components.

BACKGROUND: Despite a large body of evidence on the link between dietary inflammatory index (DII) and several chronic conditions, limited data are available about the association of DII and sarcopenia. This study aimed to examine the relationship between inflammatory potential of the diet (as measured by DII) and sarcopenia and its components among community-dwelling elderly population. METHODS: This population-based cross-sectional study was performed in 2011 among 300 elderly people (150 men and 150 women) aged ≥55 years, who were selected using cluster random sampling method. Dietary assessment was done using a pre-tested food frequency questionnaire. Energy-adjusted DII was calculated based on earlier studies. Sarcopenia and its components were determined based on the European Working Group on Sarcopenia (EWGSOP) definition. RESULTS: Mean age of study participants was 66.7 ± 7.7 y. Subjects in the highest tertile of DII score (i.e. those with a more pro-inflammatory diet) were more likely to be older (P = 0.02). The prevalence of sarcopenia (P = 0.016) and low muscle mass (P = 0.041) was significantly higher among subjects in the top tertile compared with those in the bottom tertile of DII. After adjustment for potential confounders, those with the highest DII were 2.18 times (95% CI: 1.01-4.74) more likely to have sarcopenia than those with the lowest DII. With regard to components of sarcopenia, subjects in the top tertile of DII had not significantly greater odds of low muscle mass (OR: 1.38; 95% CI: 0.72-2.63), abnormal handgrip strength (OR: 0.97; 95% CI: 0.49-1.89), and abnormal gait speed (OR: 1.61; 95% CI: 0.84-3.08) than those in the bottom tertile. CONCLUSIONS: In conclusion, a diet with more pro-inflammatory potential was associated with a greater odds of sarcopenia. Further studies are required to confirm these findings.

HDAC Inhibitors Induce BDNF Expression and Promote Neurite Outgrowth in Human Neural Progenitor Cells-Derived Neurons.

Besides its key role in neural development, brain-derived neurotrophic factor (BDNF) is important for long-term potentiation and neurogenesis, which makes it a critical factor in learning and memory. Due to the important role of BDNF in synaptic function and plasticity, an in-house epigenetic library was screened against human neural progenitor cells (HNPCs) and WS1 human skin fibroblast cells using Cell-to-Ct assay kit to identify the small compounds capable of modulating the BDNF expression. In addition to two well-known hydroxamic acid-based histone deacetylase inhibitors (hb-HDACis), SAHA and TSA, several structurally similar HDAC inhibitors including SB-939, PCI-24781 and JNJ-26481585 with even higher impact on BDNF expression, were discovered in this study. Furthermore, by using well-developed immunohistochemistry assays, the selected compounds were also proved to have neurogenic potential improving the neurite outgrowth in HNPCs-derived neurons. In conclusion, we proved the neurogenic potential of several hb-HDACis, alongside their ability to enhance BDNF expression, which by modulating the neurogenesis and/or compensating for neuronal loss, could be propitious for treatment of neurological disorders.

Exploration of Macroporous Polymeric Sponges As Drug Carriers.

Achieving high drug loading capacity and controlling drug delivery are two main challenges related to drug carriers. In this study, polymeric macroporous sponges with very high pore volume and large porosity are introduced as a new-type of drug carrier. Due to the high pore volume (285 and 166 cm3/g for the sponges with densities of 3.5 and 6.0 mg/cm3, respectively), the sponges exhibit very high drug loading capacities with average values of 1870 ± 114 and 2697 ± 73 mg/g in the present study, which is much higher than the meso and microporous drug carriers (<1500 mg/g). In order to control the release profiles, an additional poly(p-xylylene) (PPX) coating was deposited by chemical vapor deposition on the drug loaded sponge. Consequently, Artemisone (ART) release in the aqueous medium could be retarded, depending on the density of the sponge and the thickness of the coating. In future, the new 3D polymeric sponges would be highly beneficial as drug carriers for the programmed release of drugs for treatment of chronic diseases.

Effects of inclusion of licorice (Glycyrrhiza glabra L.) leaves, a tannin-containing plant, in a low-protein diet on feedlot performance and carcass characteristics of fat-tailed lambs.

The protein-sparing effect of condensed tannins (CT) was investigated in growing lambs fed a low- or high-protein diet during a 50-day period. Isocaloric diets containing 106 g crude protein/kg dry matter (DM) (low protein; LP) or 138 g crude protein/kg DM (high protein; HP) were formulated using 70 % concentrate, 15 % corn silage, and 15 % dried licorice leaves, providing CT (4.1 g/kg DM). Twenty-four crossbred male lambs (3-4 months old, 23.9 ± 5.2 kg body weight) were assigned to one of four diets: LP with polyethylene glycol (PEG; 40 g/kg DM) supplementation (LP + PEG), LP without PEG supplementation (LP - PEG), HP with PEG supplementation (HP + PEG), and HP without PEG supplementation (HP - PEG). The effect of dietary crude protein level and CT on feed intake was not significant (P > 0.05). However, a positive effect on daily gain (P < 0.001) and feed conversion ratio (FCR; P < 0.01) was observed in lambs fed with HP diets. An interaction effect between crude protein level and PEG was observed, and consequently, FCR was higher in group LP + PEG (10.1; P < 0.05) than in groups LP - PEG (7.3), HP + PEG (5.3), or HP - PEG (5.4). There was also an interaction effect between crude protein level and PEG on kidney, pelvic, and heart fat, presenting a higher relative weight in group LP + PEG (12.6 g/kg) than in group HP + PEG (9.2 g/kg; P < 0.05), but no (P > 0.05) in groups without PEG supplementation. These preliminary results suggest that the use of CT can minimize the negative effect of low-protein diets on FCR in lambs.

A systematic review and dose-response meta-analysis of prospective cohort studies on coffee consumption and risk of lung cancer.

Studies on the association between coffee consumption and risk of lung cancer have been conflicting. The aim of this study was to systematically review the current evidence on the association between coffee consumption and risk of lung cancer and to quantify this association by performing a meta-analysis. A comprehensive systematic search was performed on online databases up to July 2023 investigating the association between coffee consumption and risk of lung cancer. All prospective cohort studies reporting odds ratios (ORs), rate or risk ratios (RRs), or hazard ratios (HRs) and 95% confidence intervals (CIs) in this context were included. The overall effect size was calculated using the random-effects model and statistical between-studies heterogeneity was examined using Cochrane's Q test and I2. A total of 14 prospective cohort studies were included in this systematic review and meta-analysis. We found a significant positive association between coffee consumption and risk of lung cancer (RR: 1.28; 95% CI: 1.12, 1.47). This association remained significant when we included a pooled analysis paper and excluded 5 cohort studies (RR: 1.37; 95% CI: 1.12, 1.66). We observed no proof of significant publication bias using Egger's test (P = 0.58). Moreover, dose-response analysis showed that each one cup/day increase in coffee consumption was related with a 6% higher lung cancer risk (RR: 1.06; 95% CI: 1.03, 1.09). In conclusion, we found a significant positive association between coffee consumption and risk of lung cancer.

The functions of hydrogen sulfide on the urogenital system of both males and females: from inception to the present.

Hydrogen sulfide (H2S) is known as a chemical gas in nature with both enzymatic and non-enzymatic biosynthesis in different human organs. A couple of studies have demonstrated the function of H2S in regulating the homeostasis of the human body. Additionally, they have shown its synthesis, measurement, chemistry, protective effects, and interaction in various aspects of scientific evidence. Furthermore, many researches have demonstrated the beneficial impacts of H2S on genital organs and systems. According to various studies, it is recognized that H2S-producing enzymes and the endogenous production of H2S are expressed in male and female reproductive systems in different mammalian species. The main goal of this comprehensive review is to assess the potential therapeutic impacts of this gasotransmitter in the male and female urogenital system and find underlying mechanisms of this agent. This narrative review investigated the articles that were published from the 1970s to 2022. The review's primary focus is the impacts of H2S on the male and female urogenital system. Medline, CINAHL, PubMed, and Google scholar databases were searched. Keywords used in this review were "Hydrogen sulfide," "H2S," "urogenital system," and "urogenital tract". Numerous studies have demonstrated the therapeutic and protective effects of sodium hydrosulfide (Na-HS) as an H2S donor on male and female infertility disorders. Furthermore, it has been observed that H2S plays a significant role in improving different diseases such as ameliorating sperm parameters. The specific localization of H2S enzymes in the urogenital system provides an excellent opportunity to comprehend its function and role in various disorders related to this system. It is noteworthy that H2S has been demonstrated to be produced in endocrine organs and exhibit diverse activities. Moreover, it is important to recognize that alterations in H2S biosynthesis are closely linked to endocrine disorders. Therefore, hormones can be pivotal in regulating H2S production, and H2S synthesis pathways may aid in establishing novel therapeutic strategies. H2S possesses pharmacological effects on essential disorders, such as anti-inflammation, anti-apoptosis, and anti-oxidant activities, which render it a valuable therapeutic agent for human urogenital disease. Furthermore, this agent shows promise in ameliorating the detrimental effects of various male and female diseases. Despite the limited clinical research, studies have demonstrated that applying H2S as an anti-oxidant source could ameliorate adverse effects of different conditions in the urogenital system. More clinical studies are required to confirm the role of this component in clinical settings.

The effect of chamomile consumption on glycemic markers in humans and animals: a systematic review and meta-analysis.

Purpose: The use of natural and herbal products as alternative therapies, in conjunction with blood glucose-lowering medications, is on the rise for patients with diabetes. Our objective was to conduct a systematic review and comprehensive meta-analysis of both human and animal models to investigate the impact of chamomile consumption on glycemic control. Methods: A systematic search was conducted on all published papers from January 1990 up to January 2022 via Scopus, PubMed/Medline, Google Scholar, and ISI Web of Science. Human and animal articles evaluating the effect of chamomile on serum glycemic markers were included. We used the random-effects model to establish the pooled effect size. The dose-dependent effect was also assessed. Results: Overall, 4 clinical trials on human and 8 studies on animals met the inclusion criteria. With regard to RCTs, a favorable effect of chamomile consumption on serum fasting blood glucose (Standardized Mean Differences (SMD): -0.65, 95% CI: -1.00, -0.29, P < 0.001; I2 = 0%) and hemoglobin A1C (HbA1C) levels (SMD: -0.90, 95% CI: -1.39, -0.40, P < 0.001; I2 = 45.4%) was observed. Considering animal studies, consumption of chamomile extracts significantly reduced serum blood glucose (SMD: -4.37, 95% CI: -5.76, -2.98, P < 0.001; I2 = 61.2%). Moreover, each 100 mg/d increase in chamomile extract intervention resulted in a significantly declined blood glucose concentrations (MD: -54.35; 95% CI: -79.77, -28.93, P < 0.001; I2 = 94.8). Conclusion: The current meta-analysis revealed that chamomile consumption could exert favorable effects on serum blood glucose and HbA1C. However, additional randomized controlled trials are needed to further confirm these findings. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01345-8.

C-terminally phosphorylated p27 activates self-renewal driver genes to program cancer stem cell expansion, mammary hyperplasia and cancer.

In many cancers, a stem-like cell subpopulation mediates tumor initiation, dissemination and drug resistance. Here, we report that cancer stem cell (CSC) abundance is transcriptionally regulated by C-terminally phosphorylated p27 (p27pT157pT198). Mechanistically, this arises through p27 co-recruitment with STAT3/CBP to gene regulators of CSC self-renewal including MYC, the Notch ligand JAG1, and ANGPTL4. p27pTpT/STAT3 also recruits a SIN3A/HDAC1 complex to co-repress the Pyk2 inhibitor, PTPN12. Pyk2, in turn, activates STAT3, creating a feed-forward loop increasing stem-like properties in vitro and tumor-initiating stem cells in vivo. The p27-activated gene profile is over-represented in STAT3 activated human breast cancers. Furthermore, mammary transgenic expression of phosphomimetic, cyclin-CDK-binding defective p27 (p27CK-DD) increases mammary duct branching morphogenesis, yielding hyperplasia and microinvasive cancers that can metastasize to liver, further supporting a role for p27pTpT in CSC expansion. Thus, p27pTpT interacts with STAT3, driving transcriptional programs governing stem cell expansion or maintenance in normal and cancer tissues.

The effect of conjugated linoleic acid supplementation in comparison with omega-6 and omega-9 on lipid profile: a graded, dose-response systematic review and meta-analysis of randomized controlled trials.

Conjugated linoleic acid (CLA) is a geometrical isomer of linoleic acid, which has anti-inflammatory, anti-diabetic, anti-cancer, and anti-obesity properties. However, the studies reported inconstant results about the CLA-related effects on lipid profiles. As a result, meta-analysis and systematic review were performed to survey the CLA supplementation-related effect on lipid profile including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG). To identify the relevant research, a systematic comprehensive search was initiated on the medical databases such as Scopus and PubMed/Medline until December 2022. The overall effect size was estimated by weighted mean difference (WMD) and 95% confidence interval (CI) in a random effect meta-analysis. In the final quantitative analysis, the meta-analysis considered 35 randomized controlled trials (RCTs) with 1,476 participants (707 controls and 769 cases). The pooled results demonstrated that CLA supplementation, compared with olive oil, significantly increased serum TG levels (WMD: 0.05 mmol/L; 95% CI: 0.01 to 0.1; p = 0.04; I2 = 0.0%, p = 0.91). With regard to TC level, CLA supplementation compared with placebo significantly reduced TC concentrations (WMD: -0.08 mmol/L; 95% CI: -0.14 to -0.02; p < 0.001; I2 = 82.4%). Moreover, the non-linear dose-response analysis indicated a decreasing trend of TC serum level from the 15th week of CLA supplementation compared with olive oil (Pnon-linearity = 0.01). The present meta-analysis and systematic review of 35 RCTs showed that the CLA intervention was able to raise the level of TG in comparison to olive oil; however, it can decrease TC level compared with placebo and olive oil.