Cardiovascular Effects of Stimulators of Soluble Guanylate Cyclase Administration: A Meta-analysis of Randomized Controlled Trials.

PURPOSE OF REVIEW: Heart failure (HF) is one of the main causes of cardiovascular mortality in the western world. Despite great advances in treatment, recurrence and mortality rates remain high. Soluble guanylate cyclase is an enzyme which, by producing cGMP, is responsible for the effects of vasodilation, reduction of cardiac pre- and after-load and, therefore, the improvement of myocardial performance. Thus, a new therapeutic strategy is represented by the stimulators of soluble guanylate cyclase (sGCs). The aim of this meta-analysis was to analyze the effects deriving from the administration of sGCs, in subjects affected by HF. A systematic literature search of Medline, SCOPUS, and Google Scholar was conducted up to December 2022 to identify RCTs assessing the cardiovascular effects, as NT-pro-BNP values and ejection fraction (EF), and all-cause mortality, of the sGCs. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics. RECENT FINDINGS: The results obtained documented a statistically significant improvement in NT-proBNP values (SMD: - 0.258; 95% CI: - 0.398, - 0.118; p < 0.001) and EF (WMD: 0.948; 95% CI: 0.485, 1.411; p < 0.001) in subjects treated with sGCs; however, no significant change was found in the all-cause mortality rate (RR 0.96; 95% CI 0.868 to 1.072; I2, p = 0). The sGCs represent a valid therapeutic option in subjects suffering from HF, leading to an improvement in cardiac performance.

Regulatory effects of curcumin on nitric oxide signaling in the cardiovascular system.

The continuously rising prevalence of cardiovascular disease (CVD) globally substantially impacts the economic growth of developing countries. Indeed, one of the leading causes of death worldwide is unfavorable cardiovascular events. Reduced nitric oxide (NO) generation is the pathogenic foundation of endothelial dysfunction, which is regarded as the first stage in the development of a number of CVDs. Nitric oxide exerts an array of biological effects, including vasodilation, the suppression of vascular smooth muscle cell proliferation and the functional control of cardiac cells. Numerous treatment strategies aim to increase NO synthesis or upregulate downstream NO signaling pathways. The major component of Curcuma longa, curcumin, has long been utilized in traditional medicine to treat various illnesses, especially CVDs. Curcumin improves CV function as well as having important pleiotropic effects, such as anti-inflammatory and antioxidant, through its ability to increase the bioavailability of NO and to positively impact NO-related signaling pathways. In this review, we discuss the scientific literature relating to curcumin's positive effects on NO signaling and vascular endothelial function.

Superoxide dismutase: a key target for the neuroprotective effects of curcumin.

Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.

Clinical performance of rapid antigen tests in comparison to RT-PCR for SARS-COV-2 diagnosis in Omicron variant: A systematic review and meta-analysis.

The Omicron variant of concern has a high level of mutations in different genes that has raised awareness about the performance of immunological products such as vaccines and antigen detection kits. In this systematic review and meta-analysis, we investigated whether Omicron had a significant influence on rapid antigen test (RAT) performance in comparison to PCR. We registered this systematic review and meta-analysis in PROSPERO with the registration number CRD42022355510. We searched PubMed, Scopus, Embase, and Web of Science databases systematically to 1 August 2022. After article screening, we assessed the quality of the included studies based on the JBI checklist. Following data extraction, we performed a meta-analysis using R software. We included 18 qualified articles presenting sufficient data about RATs performance in comparison to RT-PCR in Omicron infections. The pooled specificity and sensitivity of RATs were 1.000 (0.997-1.000) and 0.671 (0.595-0.721), respectively. The FDA-approved kits showed a better performance than WHO-approved ones with a sensitivity of 0.728 (0.620-0.815). The use of RATs with nasal swabs showed a higher sensitivity compared with nasopharyngeal swabs. The sensitivity for samples with a CT-value >25 was 0.108 (0.048-0.227). Rapid antigen tests show impaired performance for COVID-19 diagnosis when the Omicron variant is circulating, particularly in samples with low viral loads.

Effect of Calebin-A on Critical Genes Related to NAFLD: A Protein-Protein Interaction Network and Molecular Docking Study.

Background: Calebin-A is a minor phytoconstituent of turmeric known for its activity against inflammation, oxidative stress, cancerous, and metabolic disorders like Non-alcoholic fatty liver disease(NAFLD). Based on bioinformatic tools. Subsequently, the details of the interaction of critical proteins with Calebin-A were investigated using the molecular docking technique. Methods: We first probed the intersection of genes/ proteins between NAFLD and Calebin-A through online databases. Besides, we performed an enrichment analysis using the ClueGO plugin to investigate signaling pathways and gene ontology. Next, we evaluate the possible interaction of Calebin-A with significant hub proteins involved in NAFLD through a molecular docking study. Results: We identified 87 intersection genes Calebin-A targets associated with NAFLD. PPI network analysis introduced 10 hub genes (TP53, TNF, STAT3, HSP90AA1, PTGS2, HDAC6, ABCB1, CCT2, NR1I2, and GUSB). In KEGG enrichment, most were associated with Sphingolipid, vascular endothelial growth factor A (VEGFA), C-type lectin receptor, and mitogen-activated protein kinase (MAPK) signaling pathways. The biological processes described in 87 intersection genes are mostly concerned with regulating the apoptotic process, cytokine production, and intracellular signal transduction. Molecular docking results also directed that Calebin-A had a high affinity to bind hub proteins linked to NAFLD. Conclusion: Here, we showed that Calebin-A, through its effect on several critical genes/ proteins and pathways, might repress the progression of NAFLD.

Targeting PCSK9 as a key player in lipid metabolism: exploiting the therapeutic and biosensing potential of aptamers.

The degradation of low-density lipoprotein receptor (LDLR) is induced by proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in elevated plasma concentrations of LDL cholesterol. Therefore, inhibiting the interactions between PCSK9 and LDLR is a desirable therapeutic goal for managing hypercholesterolemia. Aptamers, which are RNA or single-stranded DNA sequences, can recognize their targets based on their secondary structure. Aptamers exhibit high selectivity and affinity for binding to target molecules. The systematic evolution of ligands by exponential enrichment (SELEX), a combination of biological approaches, is used to screen most aptamers in vitro. Due to their unique advantages, aptamers have garnered significant interest since their discovery and have found extensive applications in various fields. Aptamers have been increasingly utilized in the development of biosensors for sensitive detection of pathogens, analytes, toxins, drug residues, and malignant cells. Furthermore, similar to monoclonal antibodies, aptamers can serve as therapeutic tools. Unlike certain protein therapeutics, aptamers do not elicit antibody responses, and their modified sugars at the 2'-positions generally prevent toll-like receptor-mediated innate immune responses. The focus of this review is on aptamer-based targeting of PCSK9 and the application of aptamers both as biosensors and therapeutic agents.

The role of natural products as PCSK9 modulators: A review.

A variety of mechanisms and drugs have been shown to attenuate cardiovascular disease (CVD) onset and/or progression. Recent researchers have identified a potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in modulating lipid metabolism and reducing plasma low density lipoprotein (LDL) levels. PCSK9 is the central protein in the metabolism of LDL cholesterol (LDL-C) owing to its major function in LDL receptor (LDLR) degradation. Due to the close correlation of cardiovascular disease with lipid levels, many in vivo and in vitro investigations are currently underway studying the physiological role of PCSK9. Furthermore, many studies are actively investigating the mechanisms of various compounds that influence lipid associated-disorders and their associated cardiovascular diseases. PCSK9 inhibitors have been shown to have significant impact in the prevention of emerging cardiovascular diseases. Natural products can effectively be used as PCSK9 inhibitors to control lipid levels through various mechanisms. In this review, we evaluate the role of phytochemicals and natural products in the regulation of PCSK9, and their ability to prevent cardiovascular diseases. Moreover, we describe their mechanisms of action, which have not to date been delineated.

Association of Chlamydia and Mycoplasma infections with susceptibility to ovarian cancer: A systematic review and meta-analysis.

BACKGROUND: Ovarian cancer is one of the most prevalent cancers with a high mortality rate in women. Published studies indicate that inflammation, DNA damage, and pelvic inflammatory disease (PID) are the most important risk factors for ovarian cancer and this could be induced and exacerbated by infectious agents such as Chlamydia trachomatis and Mycoplasma genitalium. The aim of this study was to determine the association between Chlamydia and Mycoplasma infections and the risk of ovarian cancer. METHODS: We carried out a comprehensive search of PubMed, Scopus, Web of Science, Embase, and Google Scholar without limitation on publication date. All relevant studies which investigatived probable potential connection between Chlamydia and Mycoplasma infection and development of ovarian cancer were included. RESULTS: Eighteen studies comprising a total of 8207 patients were evaluated in the study and this showed that the frequency of infection with Chlamydia and Mycoplasma among ovarian cancer patients was 32.6 % and 23 %, respectively. The results suggested that Chlamydia trachomatis infection increased the overall risk for ovarian cancer by 1.344 fold (OR: 1.344; 95 %CI: 1.19-1.50). Moreover, infection with Mycoplasma infections showed a week but not significant increased risk of ovarian cancer (OR: 1.12; 95 %CI: 0.86-1.44). However, the test for heterogeneity was significant among these studies. CONCLUSION: This study confirmed the clinical relevance of Chlamydia and Mycoplasma infection and development of the ovarian cancer risk, although the significance was marginal and study heterogeneity was significant. This highlights the need for further studies in this area.

The interaction of Helicobacter pylori with cancer immunomodulatory stromal cells: New insight into gastric cancer pathogenesis.

Gastric cancer is the fourth most common cause of cancer-linked deaths in the world. Gastric tumor cells have biological characteristics such as rapid proliferation, high invasiveness, and drug resistance, which result in recurrence and poor survival. Helicobacter pylori (H. pylori) has been proposed as a first-class carcinogen for gastric cancer according to the 1994 world health organization (WHO) classification. One of the important mechanisms by which H. pylori affects the gastric environment and promotes carcinogenesis is triggering inflammation. H. pylori induces an inflammatory response and a plethora of different signal transduction processes, leading to gastric mucosal disturbance, chronic gastritis, and a multi-step complex pathway that initiates carcinogenesis. It seems undeniable that the interaction between various cell types, including immune cells, gastric epithelium, glands, and stem cells, is vital for the progression and development of carcinogenesis concerning H. pylori. The interactions of H. pylori with surrounding cells play a key role in cancer progression. In this review, we discuss the interplay between H. pylori and tumor-supportive cells, including mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid derived-suppressor cells (MDSCs) in gastric cancer. It is hoped that clarifying the specific mechanisms for 'cross-talk' between H. pylori and these cells will provide promising strategies for developing new treatments.

Anti-inflammatory effects of sodium-glucose cotransporter-2 inhibitors in COVID-19.

The ongoing pandemic of COVID-19 is intrinsically a systemic inflammatory disorder; hence, those patients suffering an underlying chronic inflammatory disease such as diabetes mellitus are at high risk of severe complications. Preventing or suppressing the inflammatory responses are of importance in diabetic patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are a newly introduced anti-diabetic drugs that have hypoglycemic effects through the urinary excretion of glucose. They also have an anti-inflammatory potential in diabetes patients, in addition to improving glycemic control, and while there is no direct data available in diabetic patients with COVID-19 disease, there is evidence that suggests that SGLT2i can reduce systemic inflammation and diminish the cytokine storm effect via several cellular mechanisms. In the current review, our aim was to classify and describe the molecular and cellular pathways by which SGLT2i have anti-inflammatory effects in diabetic patients with COVID-19 disease.

The Effects of N-Acetyl-L-Leucine on the Improvement of Symptoms in a Patient with Multiple Sulfatase Deficiency.

Multiple Sulfatase Deficiency (MSD) is a rare autosomal recessive disease with specific clinical findings such as psychomotor retardation and neurological deterioration. No therapy is available for this genetic disorder. Previous studies have shown that N-acetyl-L-leucine (NALL) can improve the neurological inflammation in the cerebellum.In the current study, the effects of NALL on ataxia symptoms and quality of life were explored in a patient with MSD.This study was a crossover case study. The subject, a girl aged 12 years old, received NALL at a dose of 3 g/day (1 g in the morning, 1 g in the afternoon, and 1 g in the evening). A fasting blood sample was taken from the subject to evaluate side effects before the intervention and 4 weeks after taking supplement/placebo in every study stage. The ataxia moving symptoms were evaluated using the Scale for the Assessment and Rating of Ataxia (SARA) score in every study stage. Dietary intake was measured using 24-h dietary recall before and after the intervention. The diet compositions were assessed by Nutritionist IV software. Serum IL-6 level was measured using an ELISA kit.There was no significant change in complete blood count (CBC) and serum biochemical factors in the patient with MSD after receiving NALL (3 g/day) over 4 weeks. The SARA score was reduced by 25%. The gait whose maximum score accounts for approximately one-fifth of the maximum total SARA score (8/40) was decreased. The heel-to-shin slide, the only SARA item performed without visual control, was also improved after therapy. Furthermore, there was a downward trend in the 8MWT (8.71 to 7.93 s). Regarding quality of life assessments, the parent and child reported improved quality of life index, physical health, and emotional function after taking NALL. Moreover, total energy intake was increased with NALL treatment through the study period.Supplementation with NALL at a dose of 3 g/day over 4 weeks was well tolerated and improved ataxia symptoms, quality of life measure, and serum IL-6 levels in the patient with MSD. Further proof-of-concept trials are warranted to confirm the present findings.

SGLT2 inhibitors and autophagy in diabetes.

Autophagy is a physiological event in mammalian cells to promote cell survival and efficiency in tissues, but it may turn to be a pathological process in disease conditions such as in diabetes. Chronic hyperglycemia induces aberrant autophagy and promotes cellular death as a main underlying cause of diabetes-related complications. Therefore, autophagy-modifying therapy may be of value to prevent the development of complications. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of newly introduced antidiabetic drugs that achieve normoglycemia through causing overt glycosuria. There is evidence that these drugs may have pleiotropic extra-glycemic benefits, but their effect on the autophagy process is unclear; therefore, this review was undertaken to clarify the possible effects of SGLT2is on autophagy.

Long-Term Vaccination and Treatment Strategies for COVID-19 Disease and Future Coronavirus Pandemics.

The appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased infectivity and immune escape capabilities has allowed continuation of the COVID-19 pandemic for the foreseeable future. This review describes the worldwide efforts aimed at developing new vaccination and treatment strategies to keep pace with these variants as they emerge. In the case of vaccines and monoclonal antibody-based therapeutics, we describe the development of variant-specific, multivalent, and universal coronavirus directed approaches. Existing treatment approaches consist of repurposed medicines, such as antiviral compounds and anti-inflammatory agents, although efforts are underway to develop new ways of preventing or minimizing the effects of infection with the use of small molecules that disrupt binding the SARS-CoV-2 virus to host cells. Finally, we discuss the preclinical and clinical testing of natural products from medicinal herbs and spices, which have demonstrated anti-inflammatory and antiviral properties and therefore show potential as novel and safe COVID-19 treatment approaches.

Red Cell Distribution Width as a Prognostic Indicator for Mortality and ICU Admission in Patients with COVID-19.

BACKGROUND: COVID-19 disease caused by the SARS-CoV-2 virus can lead to an acute respiratory illness with a high hospitalization and mortality risk. Therefore, prognostic indicators are essential for early interventions. As a component of complete blood counts, the coefficient of variation (CV) of red blood cell distribution width (RDW) reflects cellular volume variations. It has been shown that RDW is associated with increased mortality risk in a wide range of diseases. This study aimed to determine the relationship between RDW and mortality risk in COVID-19 patients. METHODS: This retrospective study was performed on 592 patients admitted to hospital between February 2020 and December 2020. Patients were divided into low and high RDW groups and the relationship between RDW and mortality, intubation, admission to intensive care unit (ICU), and need for oxygen therapy was investigated. RESULTS: The mortality rate in the low RDW group was 9.4%, while that in the high group was 20% (p < 0.001). Also, ICU admission in the low group was 8%, whereas this was 10% in the high RDW group (p = 0.040). The results of the Kaplan-Meyer curve showed that the survival rate was higher in the low group compared to the high RDW group. Cox results in the crude model showed that higher RDW values were directly related to increased mortality, although this was not significant after adjustment for other covariates. CONCLUSION: The results of our study reveal that high RDW is associated with increased hospitalization and risk of death and that RDW may be a reliable indicator of COVID-19 prognosis.

Predicting the COVID-19 Patients Status Using Chest CT Scan Findings: A Risk Assessment Model Based on Decision Tree Analysis.

BACKGROUND: The role of chest computed tomography (CT) to diagnose coronavirus disease 2019 (COVID-19) is still an open field to be explored. The aim of this study was to apply the decision tree (DT) model to predict critical or non-critical status of patients infected with COVID-19 based on available information on non-contrast CT scans. METHODS: This retrospective study was performed on patients with COVID-19 who underwent chest CT scans. Medical records of 1078 patients with COVID-19 were evaluated. The classification and regression tree (CART) of decision tree model and k-fold cross-validation were used to predict the status of patients using sensitivity, specificity, and area under the curve (AUC) assessments. RESULTS: The subjects comprised of 169 critical cases and 909 non-critical cases. The bilateral distribution and multifocal lung involvement were 165 (97.6%) and 766 (84.3%) in critical patients, respectively. According to the DT model, total opacity score, age, lesion types, and gender were statistically significant predictors for critical outcomes. Moreover, the results showed that the accuracy, sensitivity and specificity of the DT model were 93.3%, 72.8%, and 97.1%, respectively. CONCLUSIONS: The presented algorithm demonstrates the factors affecting health conditions in COVID-19 disease patients. This model has the potential characteristics for clinical applications and can identify high-risk subpopulations that need specific prevention. Further developments including integration of blood biomarkers are underway to increase the performance of the model.

Statins: Beneficial Effects in Treatment of COVID-19.

The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important options. Various inflammatory pathways such as nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways and mediators, such as interleukin (IL)-6, IL-1ß, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ), cause cell apoptosis, reduce respiratory capacity and oxygen supply, eventually inducing respiratory system failure and death. Statins are well known for controlling hypercholesterolemia and may serve to treat COVID-19 due to their pleiotropic effects among which are anti-inflammatory in nature. In this chapter, the anti-inflammatory effects of statins and their possible beneficial effects in COVID-19 treatment are discussed. Data were collected from experimental and clinical studies in English (1998-October 2022) from Google Scholar, PubMed, Scopus, and the Cochrane Library.

Immunogenicity of Inactivated SARS-CoV-2 Vaccine (BBIBP-CorV; Sinopharm) and Short-Term Clinical Outcomes in Vaccinated Solid Organ Transplant Recipients: A Prospective Cohort Study.

BackgroundImmunocompromised patients have lower seroconversion rate in response to COVID-19 vaccination. The aim of this study is to evaluate the humoral immune response with short-term clinical outcomes in solid organ transplant recipients vaccinated with SARS-CoV-2 vaccine (BBIBP-CorV; Sinopharm).MethodsThis prospective cohort was conducted from March to December 2021 in Abu Ali Sina hospital, Iran. All transplant recipients, older than 18 years were recruited. The patients received two doses of Sinopharm vaccine 4 weeks apart. Immunogenicity was evaluated through assessment of antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 after the first and second dose of vaccine. The patients were followed up for 6 months after vaccination.ResultsOut of 921 transplant patients, 115 (12.5%) and 239 (26%) had acceptable anti S-RBD immunoglobulin G (IgG) levels after the first and second dose, respectively. Eighty patients (8.68%) got infected with COVID-19 which led to 45 (4.9%) of patients being hospitalized. None of the patients died during follow-up period. Twenty-four (10.9%) liver transplant recipients developed liver enzyme elevation, and increased serum creatinine was observed in 86 (13.5%) kidney transplant patients. Two patients experienced biopsy-proven rejection without any graft loss.ConclusionOur study revealed that humoral response rate of solid organ transplant recipients to Sinopharm vaccine was low.

The effect of nuts consumption on circulating oxidized low-density lipoproteins: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis evaluated the effect of nuts in decreasing circulating levels of oxidized low-density lipoproteins (ox-LDL). A literature search was performed of major electronic databases (MEDLINE/PubMed, Scopus, and ISI Web of Science) from inception up to November 15th, 2021 to find randomized controlled trials (RCTs) evaluating the effect of different nuts on circulating levels of ox-LDL. The effect size was determined using standardized mean difference (SMD) and corresponding 95% confidence intervals (CI). Evaluation of funnel plot, Begg's rank correlation, and Egger's weighted regression tests were used to assess the presence of publication bias in the meta-analysis. This systematic review and meta-analysis included 15 RCTs involving 997 subjects. Meta-analysis showed that nuts significantly decreased serum levels of ox-LDL. Besides, meta-regression results of the association between confounders such as duration of nuts consumption or delta LDL-cholesterol and levels of ox-LDL, were not significant. The correlation between nuts type and ox-LDL levels was significant in subgroup analyses suggesting the most significant effect of pistachios consumption on reducing the circulating concentrations of ox-LDL. To conclude, nuts consumption decreases the circulating concentrations of ox-LDL which might be beneficial for the prevention and/or progression of ASCVD.

Impact of pomegranate juice on blood pressure: A systematic review and meta-analysis.

Despite the importance of polyphenol-rich fruits in decreasing cardiovascular mortality, the impact of pomegranate juice (PJ) on blood pressure is still unclear. To determine the effect of PJ on blood pressure. PubMed, Scopus, ISI Web of Science, and Cochrane Library were searched comprehensively using relevant keywords. All studies using pomegranate juice alone were included although limited to human studies and the English language. A random-effects model and the generic inverse variance approach were used to determine quantitative data synthesis. Meta-analysis of 14 clinical trials (n = 573 individuals) demonstrated a reduction in systolic BP (SBP) with pomegranate juice (MD: -5.02 mmHg, 95% CI: -7.55 to -2.48, p < 0.001). Effect of study duration showed pomegranate juice intake ≤2 months significantly decreased SBP (MD: -4.59 mmHg, 95% CI: -7.10 to -2.08, p < 0.001) and DBP (MD: -2.94 mmHg, 95% CI: -5.25 to -0.63, p = 0.01). Consumption of ≤300 mL pomegranate juice daily reduced SBP (MD: -6.11 mmHg, 95% CI: -9.22 to -3.00, p < 0.001). Counterintuitively, >300 mL/day of pomegranate juice showed no effect on SBP (MD: -3.28 mmHg, 95% CI: -6.85 to 0.27, p = 0.07) but a significant DBP reduction occurred (MD: -3.10 mmHg, 95% CI: -5.74 to -0.47, p = 0.02). Meta-regression showed that the SBP-lowering effect of pomegranate juice was associated with the dose of supplementation (p < 0.001). Pomegranate juice appeared to decrease SBP and DBP in a dose-dependent manner, but the benefit was lost after 2 months of pomegranate juice intake.

Curcumin-piperine co-supplementation and human health: A comprehensive review of preclinical and clinical studies.

Curcumin is extracted from the rhizomes Curcuma longa L. It is known for its anti-inflammatory and anti-oxidant activities. Despite its safety and potential for use against various diseases, curcumin's utility is restricted due to its low oral bioavailability. Co-administration of curcumin along with piperine could potentially improve the bioavailability of curcumin. The present review aimed to provide an overview of the efficacy and safety of curcumin-piperine co-supplementation in human health. The findings of this comprehensive review show the beneficial effects of curcumin-piperine in improving glycemic indices, lipid profile and antioxidant status in diabetes, improving the inflammatory status caused by obesity and metabolic syndrome, reducing oxidative stress and depression in chronic stress and neurological disorders, also improving chronic respiratory diseases, asthma and COVID-19. Further high-quality clinical trial studies are needed to firmly establish the clinical efficacy of the curcumin-piperine supplement.