Effects of Posterior Tibial Nerve Stimulation on Fecal Incontinence: An Umbrella Review.

PURPOSE: This study aimed to summarize relevant data from previous systematic reviews (SRs) and conduct comprehensive research on the clinical effects of posterior tibial nerve stimulation (PTNS), via the transcutaneous posterior tibial nerve stimulation (TPTNS) or percutaneous posterior tibial nerve stimulation (PPTNS) method on fecal incontinence (FI). MATERIALS AND METHODS: In adherence to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search was conducted on PubMed, Embase, Scopus, and Web of Science databases. We included English-language, full-text SRs reporting outcomes for FI following either PPTNS or TPTNS. The quality of included studies was assessed using the Joanna Briggs Institute checklist. In addition, reanalyzing the meta-analyses was conducted using Comprehensive Meta-Analysis (CMA) software version 3.0 to achieve effect sizes and the level of statistical significance was set at p ≤ 0.05. RESULTS: From a total of 835 citations, 14 SRs met our inclusion criteria. Four of these also conducted a meta-analysis. Most SRs reported an overall improvement in different study parameters, including bowel habits and quality of life. However, there were major inconsistencies across the results. The most studied outcome was FI episodes, followed by incontinence score. The summary outcomes showed no statistically significant changes in comparing PTNS with sham or sacral nerve stimulation (SNS) for FI (p > 0.05). However, the results of subgroup analysis based on the type of intervention in the control group revealed that FI episodes were significantly fewer than in the PTNS arm, whereas PTNS led to fewer episodes of FI than did the sham. In terms of incontinence score, the results showed that PTNS compared with sham did not change the incontinence score; however, SNS improved the score significantly in one eligible study for reanalysis when compared with PTNS (p < 0.001). CONCLUSIONS: The findings of the current umbrella review suggest that PTNS can potentially benefit patients with FI. However, this is concluded from studies with a limited population, disregarding the etiology of FI and with limited follow-up duration. Therefore, caution must be taken in contemplating the results.

The effects of melatonin supplementation on neurobehavioral outcomes and clinical severity in rodent models of multiple sclerosis; a systematic review and meta-analysis.

BACKGROUND: Through the antioxidant and anti-inflammation pathways, melatonin is proposed as a safe and effective intervention in neurological diseases. This study aims to evaluate the effects of melatonin supplementation on the neurobehavioral and clinical outcomes in animal models of multiple sclerosis (MS). METHODS: This study was conducted following the PRISMA statement. Animal studies that reported the effects of melatonin in preclinical MS models, including the experimental autoimmune encephalomyelitis (EAE) and cuprizone model for demyelination are included in this study. A systematic search in PubMed, Web of Science, Embase, and Scopus up was conducted in April 2023. The collaborative Approach to Meta-Analysis and Review of Animal Experimental Studies (CAMARADES) critical appraisal tool was used for the quality assessment of the studies and the quantitative synthetizes were conducted using the comprehensive meta-analysis software. RESULTS: Out of 542 studies, finally 21 studies, including 14 studies in the EAE model and 7 studies of the toxic demyelination method with cuprizone were included. The route of administration was intraperitoneal in 18 studies, oral in 2 studies, and subcutaneous in 1 study. The quantitative synthesis of the EAE clinical severity scale was associated with significant differences (standardized mean difference [SDM]: - 2.52; - 3.61 to - 1.42; p value < 0.01). In subgroup analyses, the difference was statistically significant in the mouse subgroup (SMD: - 2.60; - 3.74 to - 1.46; p value < 0.01). DISCUSSION: This study encountered that melatonin may be associated with improved behavioral and cognitive outcomes of preclinical models of MS with acceptable safety profiles. FUNDING: The research was supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71005).

High-fat diet-induced biogenesis of pulmonary exosomes in an experimental rat model.

BACKGROUND: High-fat diets (HFD) have recently become a public health concern. We hypothesize that HFD induces exosomes biogenesis in the lung tissue of rat model. METHODS AND RESULTS: Sixteen adult male Wistar rats were fed with HFD or a regular chow diet for 3 months. The histopathological changes in lung tissues were measured by hematoxylin and eosin (H&E) staining. Bronchoalveolar lavage (BAL) was performed to assay exosomes by acetylcholinesterase enzyme (AhCE) activity. Real-time PCR (qPCR) was used to evaluate Rab27-b, Alix, and IL-1ß expression, while the immunohistochemical examination was performed for CD81 expression in lung tissues. In addition, expression of IL-1ß was detected by ELISA. We found pathological alterations in the lung tissue of HFD animals. AhCE activity along with the expression level of Rab27-b, Alix, and IL-1ß was increased in HFD animals (p < 0.05). Immunohistochemical staining showed that expression of CD81 was increased in lung tissues of HFD animals compared with the control group (p < 0.05). CONCLUSION: Hence, HFD induced exosomes biogenesis and histopathological changes with IL-1ß expression in rats' lung tissues.

Combined systemic inflammatory indexes as reflectors of outcome in patients with COVID­19 infection admitted to ICU.

INTRODUCTION: The principal etiology of mortality in COVID-19 patients is the systemic pro-inflammatory processes which may lead to acute respiratory distress syndrome. Hematologic indices are reachable representatives of inflammation in patients with COVID-19 infection. The purpose of the current study was to evaluate the potential predictive value of these inflammatory indices in the in-hospital mortality of ICU-admitted COVID-19 patients. The studied indexes included AISI, dNLR, NLPR, NLR, SII, and SIRI. METHOD: 315 COVID-19 patients admitted to ICU managed in Imam Khomeini Hospital of Urmia, Iran, during the last 6 months of 2020 were retrospectively enrolled in the study and divided into two subgroups based on their final outcome, discharge or death. RESULTS: Total leucocyte count (TLC), absolute neutrophil count (NLC), urea, Cr, RDW, AISI, dNLR, NLPR, NLR, SII, and SIRI were drastically elevated in the dead patients (P < 0.05). The optimal cut-off points for AISI (378.81), dNLR (5.66), NLPR (0.03), NLR (5.97), SII (1589.25), and SIRI (2.31) were obtained using ROC curves. NLR and SII had the highest sensitivity (71.4%) and specificity (73.6%), respectively. Patients with above-cut-off levels of ISI, dNLR, NLPR, NLR, and SII had lower average survival time. Age (OR = 1.057, CI95%: 1.030-1.085, p < 0.001) and dNLR (OR = 1.131, CI95%: 1.061-1.206, p < 0.001) were the independent predictors for mortality in the studied COVID-19 patients based on multivariate logistic regression. CONCLUSION: Age and dNLR are valuable predictive factors for in-hospital death of ICU-admitted COVID-19 patients. Besides, other indices, AISI, NLPR, NLR, SII, and SIRI, may have an additional role that requires further investigation.

Exosome-based strategies for diagnosis and therapy of glioma cancer.

Glioblastoma belongs to the most aggressive type of cancer with a low survival rate that is characterized by the ability in forming a highly immunosuppressive tumor microenvironment. Intercellular communication are created via exosomes in the tumor microenvironment through the transport of various biomolecules. They are primarily involved in tumor growth, differentiation, metastasis, and chemotherapy or radiation resistance. Recently several studies have highlighted the critical role of tumor-derived exosomes against immune cells. According to the structural and functional properties, exosomes could be essential instruments to gain a better molecular mechanism for tumor understanding. Additionally, they are qualified as diagnostic/prognostic markers and therapeutic tools for specific targeting of invasive tumor cells such as glioblastomas. Due to the strong dependency of exosome features on the original cells and their developmental status, it is essential to review their critical modulating molecules, clinical relevance to glioma, and associated signaling pathways. This review is a non-clinical study, as the possible role of exosomes and exosomal microRNAs in glioma cancer are reported. In addition, their content to overcome cancer resistance and their potential as diagnostic biomarkers are analyzed.

Induction of chronic asthma up regulated the transcription of senile factors in male rats.

BACKGROUND: The main characteristic of asthma is chronic inflammation. We examined cellular senescence by histology and molecular assay in the lungs of a rat model of asthma. This model comprises sensitization by several intraperitoneal injections of ovalbumin with aluminium hydroxide, followed by aerosol challenges every other day. RESULTS: Data showed that asthma induction caused histological changes including, hyperemia, interstitial pneumonia, fibrinogen clots, and accumulation of inflammatory cells in the pleura. There is an elevation of IL-1ß and NF-kB proteins in the asthmatic group (P < 0.001) compared to the control group. The expression of ß-galactosidase increased (P < 0.01), while the expression of Klotho and Sox2 genes was decreased in the lung tissue of the asthmatic group (P < 0.01). CONCLUSION: Taken together, these findings suggest that asthmatic conditions accelerated the cellular senescence in the lung tissue.

Serum lipids and cognitive outcomes in multiple sclerosis; a systematic review and meta-analysis.

BACKGROUND: Cognitive impairment is highly prevalent in multiple sclerosis (MS) with poorly understood underlying mechanisms. Lipids are considered to be associated with MS progression through the inflammatory and oxidative stress pathways, brain atrophy, cellular signaling, and tissue physiology. In addition, serum lipids are proposed as a modifiable factor affecting the neuropsychiatric condition; therefore, this study aims to assess the association between serum lipid levels and cognitive outcomes in MS. METHODS: This study was carried out following the PRISMA 2020 statement. A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase in March 2023, and the Joanna Briggs Institute (JBI)'s critical appraisal tools were utilized for risk of bias (RoB) assessments in the included studies. The quantitative synthesis was performed with the comprehensive meta-analysis (CMA3) software. RESULTS: Out of 508 screened records, 7 studies were eventually found to meet our inclusion criteria. In two studies, the course of MS in the sample of the study was only Relapsing-Remitting MS (RRMS), whereas the other five studies' sample was a combination of different phenotypes. Studies utilized different scales such as Minimal Assessment of Cognitive Function in MS (MACFIMS), Brief International Cognitive Assessment for MS (BICAMS), Montreal Cognitive Assessment (MoCA), Brief Repeatable Battery of Neuropsychological Tests (BRB-N) for cognitive evaluations. Dealing with possible confounders such as age, disease duration and level of disability was the most common possible source of bias in the included studies. One study revealed an inverse relationship between serum levels of apolipoproteins (including ApoA-I, ApoB, and ApoB/ApoA-I) and Symbol Digit Modalities Test (SDMT) scores. Also, a correlation between 24S-hydroxycholesterol (24OHC) serum concentrations and SDMT score was reported in one study. The association between serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) and different aspects of cognitive function was reported in the studies; however, serum levels of high-density lipoprotein cholesterol (HDL) were not found to be associated. The quantitative synthesis revealed a significant correlation between TC and the MoCA scores (r =-0.238; 95 %CI: -0.366 to -0.100; p-value = 0.001); however, the correlation between TG levels and MoCA were not statistically significant (r:-0.070; 95 %CI: -0.209 to 0.072; p-value: 0.334). In addition, the mata-analyses were not associated with significant findings regarding the correlation between lipid profiles (including HDL, LDL, TG, and TC) and other cognitive assessment scales including SDMT, Brief Visuospatial Memory Test (BVMT), and California Verbal Learning Test (CVLT) (p-values>0.05). DISCUSSION: Available evidence suggested a link between TC and LDL with cognitive outcomes of MS patients which was not evident in our quantitative synthesis. The limited number of studies, high RoB, different cognitive assessment scales and reporting methods, and the cross-sectional design of the included studies, were the main limitations that alleviate the clinical significance of the findings of this study and suggested further investigations on this topic. FUNDING AND REGISTRATION: The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71,909). This study is registered in the international prospective register of systematic reviews (PROSPERO ID: CRD42023441625).

Shining a Light on Selenium: a Meta-analysis of Supplementation in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system. Selenium is a trace element with significant antioxidant activity. This study aimed to seek evidence concerning selenium supplementation in MS. A systematic search was performed on PubMed, Web of Science, Scopus, and Embase databases to identify the studies assessing the consumption rate, efficacy, and safety of selenium and selenium-containing supplementations in MS patients. The meta-analysis was performed using the Comprehensive Meta-Analysis and the risk of bias was evaluated using the Joanna Briggs Institute's critical appraisal tools. A total of 9 studies were included, which consisted of six studies regarding the rate of selenium supplement consumption in MS patients, with a total sample size of 2381 patients. Based on the quantitative synthesis, 14.3% (95% CI, 12.8-16.0%; I2, 3.58%) of MS patients had current selenium supplements usage, and 11.3% (95% CI, 7.6-16.6%; I2, 81.40%) of patients had used selenium supplements previously. Although there is no evidence regarding supplementation with selenium alone, three RCT studies reported the safety of selenium-containing supplementation use in MS with improved inflammation and oxidative stress conditions. The findings of this study show that over 10% of patients with MS used selenium supplements, with no clinical significance supporting the benefits. There is a lack of evidence regarding the safety and efficacy of selenium supplements in MS patients. Due to the limited number of included studies and the lack of comprehensive and specific studies regarding selenium supplements in MS, the results must be interpreted with caution, and future clinical trials are required.

A systematic review of clinical efficacy and safety of cell-based therapies in Alzheimer's disease.

There is presently no disease-modifying therapy for Alzheimer's Disease (AD), which is the most prevalent cause of dementia. Objective: This study aspires to estimate the efficacy and safety of cell-based treatments in AD. Methods: Observing the Joanna Briggs Institute (JBI) methods and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a systematic search was accomplished in PubMed, Medical Literature Analysis and Retrieval System Online (Medline, via Ovid), Embase; Cochrane, and Cumulative Index of Nursing and Allied Health Literature - CINAHL (via EBSCO) databases up to June 2023. The relevant clinical studies in which cell-based therapies were utilized to manage AD were included. The risk of bias was evaluated using the JBI checklists, based on the study designs. Results: Out of 1,014 screened records, a total of five studies with 70 individuals (including 59 patients receiving stem cells and 11 placebo controls) were included. In all these studies, despite the discrepancy in the origin of stem cells, cell density, and transplant site, safety goals were obtained. The intracerebroventricular injection of adipose-derived stromal vascular fraction (ADSVF) and umbilical cord-derived mesenchymal stem cells (UC-MSCs), the intravenous injection of Lomecel-B, and the bilateral hippocampi and right precuneus injection of UC-MSCs are not linked to any significant safety concerns, according to the five included studies. Studies also revealed improvements in biomarkers and clinical outcomes as a secondary outcome. Three studies had no control groups and there are concerns regarding the similarity of the groups in others. Also, there is considerable risk of bias regarding the outcome assessment scales. Conclusion: Cell-based therapies are well tolerated by AD patients, which emphasizes the need for further, carefully planned randomized studies to reach evidence-based clinical recommendations in this respect.

Atualmente, não há terapia modificadora da doença para a doença de Alzheimer (DA), que é a causa mais prevalente de demência. Objetivo: Este estudo teve como objetivo estimar a eficácia e segurança dos tratamentos baseados em células na DA. Métodos: Observando os métodos do JBI e a declaração PRISMA, uma busca sistemática foi realizada nas bases de dados PubMed, Medical Literature Analysis and Retrieval System Online ­ Medline (via Ovid), Embase, Cochrane e CINAHL (via EBSCO) até junho de 2023. Foram incluídos os estudos clínicos relevantes nos quais terapias baseadas em células foram utilizadas para gerenciar a DA. O risco de viés foi avaliado utilizando os checklists do JBI, com base nos desenhos dos estudos. Resultados: Dos 1.014 registros examinados, foi incluído um total de cinco estudos com 70 indivíduos (incluindo 59 pacientes que receberam células-tronco e 11 controles de placebo). Em todos esses estudos, apesar da discrepância na origem das células-tronco, densidade celular e local de transplante, os objetivos de segurança foram alcançados. A injeção intracerebroventricular de ADSVF e UC-MSCs, a injeção intravenosa de Lomecel-B e a injeção bilateral dos hipocampos e precuneus direito de UC-MSCs não estão relacionadas a quaisquer preocupações significativas de segurança, de acordo com os cinco estudos incluídos. Os estudos também revelaram melhorias nos biomarcadores e resultados clínicos como um desfecho secundário. Três estudos não tinham grupos de controle e há preocupações quanto à semelhança dos grupos em outros. Além disso, há um risco considerável de viés em relação às escalas de avaliação de desfechos. Conclusão: As terapias baseadas em células são bem toleradas por pacientes com DA, o que enfatiza a necessidade de mais estudos randomizados cuidadosamente planejados para alcançar recomendações clínicas baseadas em evidências.

The Hepatoprotective Effects of Ginsenoside from Ginseng: A Review of Molecular Mechanisms and Therapeutic Potentials.

Treatment of hepatic diseases presents a significant challenge due to their diverse nature. Ginsenosides, bioactive compounds derived from the root of Panax ginseng and widely used in traditional Chinese medicine, offer multifaceted protection to various organs in the body. Their versatile effects, including antioxidant, anti-inflammatory, anti-apoptotic and more, make them a promising approach for addressing hepatic disorders. This review explores the intricate molecular mechanisms and properties of ginsenosides in the prevention and treatment of liver ailments, from mild conditions to severe damage and liver fibrosis. Given the increasing prevalence of hepatic disorders, this article sheds light on the significant pharmaceutical potential of ginsenosides in the realm of hepatic disease management.

Potential promising anticancer applications of ß-glucans: a review.

ß-Glucans are valuable functional polysaccharides distributed in nature, especially in the cell walls of fungi, yeasts, bacteria, and cereals. The unique features of ß-glucans, such as water solubility, viscosity, molecular weight, and so on, have rendered them to be broadly applied in various food systems as well as in medicine to improve human health. Moreover, inhibition of cancer development could be achieved by an increase in immune system activity via ß-glucans. ß-glucans, which are part of a class of naturally occurring substances known as biological response modifiers (BRMs), have also shown evidence of being anti-tumorogenic, anti-cytotoxic, and anti-mutagenic. These properties make them attractive candidates for use as pharmaceutical health promoters. Along these lines, they could activate particular proteins or receptors, like lactosylceramide (LacCer), Dickin-1, complement receptor 3 (CR3), scavenge receptors (SR), and the toll-like receptor (TLR). This would cause the release of cytokines, which would then activate other antitumor immune cells, like macrophages stimulating neutrophils and monocytes. These cells are biased toward pro-inflammatory cytokine synthesis and phagocytosis enhancing the elicited immunological responses. So, to consider the importance of ß-glucans, the present review introduces the structure characteristics, biological activity, and antitumor functions of fungal ß-glucans, as well as their application.

Consciousness Recovery in Traumatic Brain Injury: A Systematic Review Comparing Modafinil and Amantadine.

OBJECTIVES: Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs. METHODS: This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases. Extensive searches were conducted separately by 4 individuals in 3 stages. Ultimately, 16 clinical trials, cohort studies, case reports, and case series articles were obtained after reading the title, abstract, and full text and considering the exclusion criteria. The data of the final article were entered into the analysis table. This study was registered with PROSPERO (registration number CRD42022334409) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Amantadine seems to be associated with a higher overall response rate. In contrast, modafinil is associated with the most remarkable change in GCS score during treatment. However, the number of clinical trials with high quality and sample size has not been satisfactory to compare the effectiveness of these 2 drugs and their potential side effects. CONCLUSIONS: The authors recommend additional double-blind clinical trials are needed to be conducted with a larger sample size, comparing amantadine with modafinil to delineate the efficacy and adverse effects, both short and long term.

Development, Characterization, and In Vitro Evaluation of Cytotoxic Activity of Rutin Loaded PCL-PEG Nanoparticles Against Skov3 Ovarian Cancer Cell.

BACKGROUND AND PURPOSE: Rutin (RUT) is one of the phenolic compounds found in the invasive plant species, Carpobrotus edulis. Several studies have confirmed numerous pharmacological properties of RUT, including antioxidant, antidiabetic, anti-inflammatory, antimicrobial and anticancer activities. As a result, the goal of this work was to make RUT-loaded PCL-PEG and test its anti-cancer effects against the Skov3 human ovarian cancer cell line. MATERIALS AND METHODS: The NPs were made using the W1/O/W2 process, and their physicochemical properties were assessed by FE-SEM, FTIR, and DLS. MTT assay were used to investigate the anti-proliferative characteristics of drug-loaded NPs. Real-time PCR was also utilized to  examine the expression levels of apoptotic genes including caspase-8, -9, -3, and Bax, as well as anti-apoptotic genes like Bcl-2. RESULTS: Cytotoxicity testing revealed that RUT-loaded PCL-PEG improved cytotoxicity in a dose- and time-dependent manner. In treated MDA-MB-231 cells with RUT-loaded PCL-PEG, there was a significant up-regulation of caspase-8, -9, -3, and Bax genes compared to treated cells with free RUT. CONCLUSION: Finally, RUT-loaded PCL-PEG NPs are recommended as ideal delivery nanocarriers for enhancing RUT's anticancer characteristics for ovarian cancer treatment.