Clinical Implications and Prognostic Value of Leucine-Rich G Protein-Coupled Receptor 5 Expression as A Cancer Stem Cell Marker in Malignancies: A Systematic Review and Meta-Analysis.

Leucine-rich G protein-coupled receptor 5 (LGR5) is a marker of cancer stem cells (CSCs) in various cancers. Based on different studies, conflicting reports exist on correlation between LGR5 expression and poor prognosis/ clinicopathological parameters in cancer patients. Therefore, our purpose in conducting this study was to investigate correlation between LGR5 expression and outcomes of cancer patients under study through a systematic review and meta-analysis. Relevant articles were searched and collected using EMBASE, PubMed, Science Direct, and Scopus databases until December 21, 2022. This study was conducted to examine correlation between LGR5 expression and different clinical outcomes, such as recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), and clinicopathological characteristics of the included cancer patients. To achieve this, hazard ratios (HRs) with 95% confidence intervals (CIs) and odds ratios (ORs) with 95% CIs were used as statistical measures. A meta-analysis was conducted using STATA 12.0 software. Finally, 53 studies including 9523 patients met the inclusion criteria. Significantly, high-level expression of LGR5 was related to poor prognosis in terms of OS, higher tumor stage, presence of distant metastasis, and presence of lymph node metastasis. It was discovered through subgroup analysis that several factors, including the study area, evaluation method, and type of cancer, can influence the correlation between LGR5 expression and negative prognosis in cancer patients. According to the results of our study, LGR5 overexpression was related to poor OS in cancer patients. In addition, clinicopathological data indicated an unfavorable prognosis in cancer patients with high LGR5 expression. In conclusion, LGR5 may serve as a potential prognostic marker for predicting survival in certain cancer types.

Status of integrin subunit alpha 4 promoter DNA methylation in colorectal cancer and other malignant tumors: a systematic review and meta-analysis.

Background and purpose: Although many recent studies have analyzed the validation of integrin subunit alpha 4 (ITGA4) biomarker for cancer detection in patients with various malignancies, the diagnostic value of ITGA4 methylation for malignant tumors remains uncertain. We performed a systematic review and meta-analysis to unravel the relationship between ITGA4 promoter methylation status and malignant tumors. Experimental approach: A meta-analysis was performed using the metaphor package in R 3.5 and Meta-Disc 1.4 software. Data were derived from a search of main electronic databases up to January 2022. SROC analysis was used to evaluate the status of ITGA4 promoter methylation in colorectal cancer (CRC) and other cancers. A total of 1232 tumor samples and 649 non-tumor samples from 13 studies were analyzed. Findings/Results: The pooled results including all types of cancer provided evidence that ITGA4 hypermethylation was more frequent in tumor samples than non-tumor samples (OR 13.32, 95% CI 7.96-22.29). Methylation of ITGA4 has a pooled sensitivity of 0.95 (95% CI: 0.94-0.97), a pooled specificity of 0.57 (95% CI: 0.54-0.60), and an area under the curve (AUC) of 0.94. When the analysis was performed independently for CRC, it revealed a higher association (OR = 20.77, 95% CI: 9.15-47.15). The assessment of ITGA4 methylation of tissue samples resulted in a pooled sensitivity of 0.99 (95% CI: 0.97-1.00) and a pooled specificity of 0.90 (95% CI: 0.86-0.93), and AUC of 0.94 for the diagnosis of CRC. Conclusion and implications: ITGA4 methylation analysis is a reliable method for CRC screening in tissue samples.

Unfavorable prognosis and clinical consequences of APOBEC3B expression in breast and other cancers: A systematic review and meta-analysis.

INTRODUCTION: Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis, and chemotherapy drug resistance in cancers. Here we conducted a systematic review and meta-analysis to determine its prognostic value and clinicopathological features in breast cancer and some other malignancies. MATERIALS AND METHODS: PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE were searched up to Feb 2022 for the association of A3B with breast, ovarian, gastrointestinal and lung cancers. The pooled hazard ratios with 95% confidence interval (CI) were evaluated to assess disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) in cancers under study. RESULTS: Over 3700 patients were included in this meta-survey. Elevated levels of A3B were significantly related to low OS (pooled HR = 1.30; 95% CI:1.09-1.55, P < 0.01), poor DFS (pooled HR = 1.66; 95% CI:1.17-2.35, P < 0.01) and poor RFS (HR = 1.51, 95% CI:1.11-2.04, P = 0.01). Subgroup analysis revealed that high A3B expression was associated with poor OS in lung (HR = 1.85, 95% CI: 1.40-2.45), and breast cancers (HR = 1.38, 95% CI: 1.00-1.89). High expression of A3B did not display any significant association with clinicopathologic features. CONCLUSION: APOBEC3B overexpression is related to poor OS, DFS and RFS only in some cancer types and no generalized role could be predicted for all cancers.

The global prevalence of autism spectrum disorder: a comprehensive systematic review and meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is one of the serious developmental disorders that is usually diagnosed below the age of three years. Although the severity of the disease's symptoms varies from patient to patient, the ability to communicate with others is affected in all forms of ASD. This study aimed to determine the prevalence of ASD in high-risk groups by continent. METHODS: The present study was conducted by systematic review and meta-analysis from 2008 to July 2021. Databases such as Science Direct, PubMed, Scopus, SID, Magiran, Web of Science (WoS), and Google Scholar from 2008 to July 2021 were searched to find related studies. Data were analysed using Comprehensive Meta-Analysis software (Version 2). RESULTS: A total of 74 studies with 30,212,757 participants were included in this study. The prevalence of ASD in the world was 0.6% (95% confidence interval: 0.4-1%). Subgroup analyses indicated that the prevalence of ASD in Asia, America, Europe, Africa and Australia was 0.4% (95% CI: 0.1-1), 1% (95% CI: 0.8-1.1), 0.5% (95% CI: 0.2-1), 1% (95% CI: 0.3-3.1), 1.7% (95% CI: 0.5-6.1) respectively. CONCLUSION: ASD imposes a heavy health burden on communities around the world. Early detection of ASD can reduce the incidence of developmental disorders and improve patients' communication skills. Therefore, health policymakers need to be aware of the prevalence and increasing trend of ASD to implement appropriate planning and interventions to reduce its consequences.

The global prevalence of major depressive disorder (MDD) among the elderly: A systematic review and meta-analysis.

BACKGROUND: Major depressive disorder is characterized by a depressed mood or feeling of sadness, loss of interest or pleasure in everyday activities. Depressed individuals have a cognitive impairment, low self-esteem, difficulty making decisions, feeling helpless and hopeless. The factors that have been associated with depression include the lack of social support, living in rural areas, suffering from chronic diseases, smoking, and alcohol abuse. This study aimed to investigate the global prevalence of major depressive disorder in the elderly. METHOD: The electronic database such as Web of Science (WoS), Scopus, SID, PubMed, Google Scholar, Mag Iran, and IranDoc were systematically searched for studies reporting the prevalence of major depressive disorderin the elderly published up to March 2021. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) software. Heterogeneity between the studies was evaluated using the I2 index. Begg and Mazumdar rank correlation test was used to assess publication bias. RESULT: A total of 20 studies involving 18953 participants were included in this study. The global prevalence of major depression in the elderly was 13.3 % (95 % CI: 8.4-20.3 %). In the subgroup analysis, the prevalence of major depression in elderly women was 11.9 % (95 % CI: 7.6-18.6) and men 9.7 % (95 % CI: 5.2-17.3). No comparison was made between the two sexes, but based on the confidence intervals and large overlap, the two groups are not statistically different. Among continents, Australia had the highest prevalence of major depression in the elderly at 20.1 % (CI: 14.5-27.2 %). This was followed by Europe at 12.9 % (95 % CI: 5.1-28.9 %). CONCLUSION: Major depressive disorder has a growing trend in the elderly population of the world. The prevalence of major depression in the elderly depends on various clinical and demographic factors such as age and gender. Therefore, mental health and the quality of life (QoL) of the elderly are important. The present study emphasizes the importance of social support in mental health that can reduce depression in the elderly.

Anti-cancer Activity of Chrysin in Cancer Therapy: a Systematic Review.

Chrysin is a natural bioactive compound that is extracted from many trees, honey, and propolis. Chrysin has several pharmacological activities such as anti-inflammatory, anti-cancer, and antioxidant properties. This study was performed to evaluate the anti-cancer activities of chrysin in cancer therapy. The present study was conducted by systematic review of studies published up to August 2021. Related studies were identified by searching Web of Science (WoS), PubMed, Science Direct, SID, MagIran, Scopus, and Google Scholar databases. The keywords of chrysin, cancer, anti-cancer, and cancer therapy were used for searching. The quality of the studies was assessed by the CONSORT checklist. A total of 21 studies were identified. The results of studies showed that chrysin has an anticancer effect by stimulating apoptosis in a wide range of human cells and rats. Chrysin is also an important factor in inhibiting tumor growth and neoplasticity. Chrysin inhibits the growth and proliferation of cancer cells by inducing cytotoxic effects. Therefore, due to the antitumor effects of chrysin and its safety and non-toxicity towards normal cells, this compound can be considered as an adjuvant along with chemotherapeutic agents in cancer treatment.

Association of Three Functional Polymorphisms in the NLRP3 Gene with Susceptibility to Rheumatoid Arthritis in the Iranian Population.

BACKGROUND: Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation of innate immunity and its upregulation has previously been reported in RA. OBJECTIVE: To evaluate the correlation between 3 functional polymorphisms of NLRP3 and its gene expression and RA risk. METHOD: One hundred and fourteen patients with RA and 120 healthy participants were recruited to this case-control study. Genotyping of rs4612666 (intronic variant), rs10754558 (3UTR variant), and rs6672995 (downstream variant) were performed applying the real­time polymerase chain reaction high­resolution melting (HRM) method. RESULTS: Based on logistic regression analysis, subjects with CC genotype and C allele in rs4612666 had increased risk of RA (OR for CC genotype= 3.10; 95%CI [1.78-8.26]/ OR for C allele= 2.00; 95%CI [1.45-3.10]). Furthermore, in the patient groups, there was a significant relationship between the concentration of C-reactive protein (CRP) and rs4612666 and rs10754558 polymorphism (p < 0.05). Besides, our results revealed no significant association between the genotype and allele frequency of rs10754558 and rs6672995 and the risk of RA (P> 0.05). CONCLUSION: Our findings propose a significant association between rs4612666 polymorphism and increased risk of RA in the Iranian population. Moreover, rs4612666 and rs10754558 were correlated with disease activity.

The effects of exogenous application of melatonin on the degradation of polycyclic aromatic hydrocarbons in the rhizosphere of Festuca.

The study aimed to assess the effects of melatonin, a plant growth regulator, on the degradation of phenanthrene (Phe) and pyrene (Py), in the rhizosphere of the Festuca grass. The experiments were divided into the following groups: 1) soil contaminated with Phe and Py, without the Festuca, 2) contaminated soil + Festuca, 3-5), contaminated soil + Festuca + the application of melatonin in three separate doses: 10, 50, or 100 µM. After 90 days, the effects of melatonin supplementation on the degradation of polycyclic aromatic hydrocarbons (PAHs) were analyzed by evaluating the rate of PAHs degradation, the expression of genes encoding salicylaldehyde dehydrogenase (SDH) and glutathione peroxidase (GPX) enzymes in Pseudomonas putida, as well as by measuring the total activity of dehydrogenase and peroxidase enzymes. Our results have shown that in soil contaminated by 300 mg kg-1 PAHs, application of melatonin (10, 50, 100 µM), resulted in the following increase in the dehydrogenase and peroxidase activity in all three applied doses (19% and 5.7%), (45.3% and 34.3%), (40.9% and 14.3%), respectively in comparison to the control group. The experiment showed that soil supplementation with melatonin at 50 µM, resulted in the highest removal rate of PAHs. According to our results, melatonin demonstrated a potentially favorable role in enhancing plant biomass, as well as an increase in soil bacterial population, and the activity of antioxidative enzymes in P. putida, causing all tested parameters of the soil and the expression of desired genes to be advantageously altered for the degradation of the chosen PAHs.

Association of serum and follicular fluid leptin and in vitro Fertilization/ ICSI outcome: A systematic review and meta-analysis.

There are conflicting reports regarding circulating leptin and its relationship between pregnancy outcomes in infertile women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). We performed a systematic review and meta-analysis to assess the association between serum or follicular fluid (FF) leptin concentrations reported for infertile women and their IVF outcome. A systematic search was undertaken in available databases (PubMed, Scopus, Web of Science, The Cochrane Library and Embase) to find studies published up to Aug 2020 and the standardized mean difference with 95 % confidence interval was taken from 14 eligible studies. Both graphical (funnel plots) and test methods (Egger's regression test and the Begg) assessed the presence of publication bias. Subgroup analysis was used to investigate the source of heterogeneity. Pooled effect sizes based on the eligible papers indicated that of there is no statistically significant correlation between leptin levels in follicular fluid and serum on the day of ovum pick-up (OPU) and day of HCG (human chorionic gonadotrophin) administration in pregnant and non-pregnant women who underwent IVF/ICSI cycles. However, combination of leptin in serum and/or FF with other parameters may be a useful marker to predict IVF outcome.

Efficacy of insulin targeted gene therapy for type 1 diabetes mellitus: A systematic review and meta-analysis of rodent studies.

Diabetes mellitus (DM) is a major worldwide public health challenge, for which gene therapy offers a potential therapeutic approach. To date, no systematic review or meta-analysis has been published in this area, so we examined all relevant published studies on rodents to elucidate the overall effects of gene therapy on bodyweight, intraperitoneal glucose tolerance test (IPGTT), fasting blood glucose, and insulin in animals with type 1 DM. The Cochrane Library, PubMed, Embase, ISI Web of Science, SCOPUS, and Google Scholar were systematically searched for potentially relevant studies. Mean±standard deviation (SD) was pooled using a random-effects model. After the primary search, out of 528 studies identified, 16 studies were in concordance with predefined criteria and selected for the final assessment. Of these, 12 studies used viral manipulation, and 4 employed non-viral vectors for gene delivery. The meta-analysis showed gene therapy with a viral vector decreased mean IPGTT (-12.69 mmol/l, P<0.001), fasting blood glucose (-13.51 mmol/l, P<0.001), insulin (398.28 pmol/l, P<0.001), and bodyweight (24.22 g, P<0.001), whereas non-viral vectors reduced fasting glucose (-29.95 mmol/l, P<0.001) and elevated insulin (114.92 pmol/l, P<0.001). Gene therapy has favorable effects on alleviating type 1 DM related factors in diabetic rodents.

Mycological aspects of onychomycosis in Khuzestan Province, Iran: A shift from dermatophytes towards yeasts.

BACKGROUND AND PURPOSE: Onychomycosis is fungal infection of the nails with an overall increasing incidence, worldwide. The epidemiological aspects of onychomycosis in Khuzestan, Iran, have not been established. In this study, we aimed to evaluate the clinical and mycological status of fungal nail infection in Khuzestan Province, Iran. MATERIALS AND METHODS: The study population included 433 patients (143 males vs. 290 females). Nail samples underwent primary direct microscopy and culture. The isolated yeasts and dermatophytes were then subjected to additional molecular identification by r-DNA ITS-RFLP. Identification of some non-dermatophytic molds (NDMs) and unknown yeasts was accomplished by ITS and beta-tubulin sequencing. RESULTS: Onychomycosis was confirmed in 154 patients (males: 36.4%; n=56 vs. females: 63.6%; n=98), whose age ranged from 2 to 85 years, with the highest prevalence in the age group of 41-50 years. Infection mostly occurred due to yeasts (57.15%), with Candida albicans as the most frequent (29.35%) species, followed by C. parapsilosis (13.8%) and C. tropicalis (4.5%). Dermatophytes were isolated in 38.35% of the cases; the most common isolates were found to be Trichophyton interdigitale (21.1%), Epidermophyton floccosum (10.5%), T. rubrum (5.25%), and Microsporum canis (1.5%). NDMs were isolated from 4.5% of the cases with Aspergillus spp. as the most common agent. Dermatophytes and NDMs were more frequently seen in toenails, whereas yeasts mostly infected fingernails. Fingernail onychomycosis was significantly more prevalent among females than in males (P<0.05). CONCLUSION: The study highlights that in Khuzestan province, the causative agents of onychomycosis have shifted from dermatophytes to yeasts.

Dermatophytosis due to Microsporum incurvatum: Notification and Identification of a Neglected Pathogenic Species.

A 4-year-old Iranian boy developed erythematous, itchy and annular lesion on his face. Microscopic examination of the scraped samples with 10 % potassium hydroxide (KOH) revealed fungal septate hyphae and arthroconidia. The etiological agent was found to be Microsporum gypseum in mycological examinations. Amplification and restriction digestion of the internal transcribed spacers (ITS) of rDNA was not helpful for identification, but in ITS sequencing the isolate showed 98 % homology to Microsporum incurvatum strain CBS 172.64. Empirical treatment of the patient with griseofulvin for 4 weeks was successful. Other than our isolate, the ITS1 sequences of 38 strains from related species were retrieved from GenBank and phylogenetic tree using maximum likelihood method was constructed. The case isolate clustered apart from other strains of M. incurvatum. Pairwise comparison of ITS1 showed intraspecies variations of 0-13 nucleotides among M. incurvatum strains and an extensive interspecies variation of 33-80 bp and remarkable interspecies size polymorphism between the three sister species in the M. gypseum complex. The high level of ITS1 intraspecific variation is suitable for species identification rather than phylogeographic analysis of M. gypseum complex.

Design and Antigenic Epitopes Prediction of a New Trial Recombinant Multiepitopic Rotaviral Vaccine: In Silico Analyses.

Rotavirus is the major etiologic factor of severe diarrheal disease. Natural infection provides protection against subsequent rotavirus infection and diarrhea. This research presents a new vaccine designed based on computational models. In this study, three types of epitopes are considered-linear, conformational, and combinational-in a proposed model protein. Several studies on rotavirus vaccines have shown that VP6 and VP4 proteins are good candidates for vaccine production. In the present study, a fusion protein was designed as a new generation of rotavirus vaccines by bioinformatics analyses. This model-based study using ABCpred, BCPREDS, Bcepred, and Ellipro web servers showed that the peptide presented in this article has the necessary properties to act as a vaccine. Prediction of linear B-cell epitopes of peptides is helpful to investigate whether these peptides are able to activate humoral immunity.