Beyond biomarkers: Exploring the diverse potential of a novel phosphoprotein in lung cancer management.

In addressing the challenges of lung cancer, attention has increasingly turned to molecular diagnostics and targeted therapies, with nucleolin (NCL) assuming a pivotal role, especially in non-small cell lung cancer. The aberrant activity and cellular distribution of NCL act as crucial biomarkers for early detection and treatment monitoring, showing a strong correlation with disease progression and patient prognosis. Elevated NCL levels signal advanced disease and poorer outcomes, underscoring its significance in evaluating disease severity and therapeutic response. Strategies targeting the molecular interactions of NCL have spurred innovative approaches to inhibit tumour growth, overcome drug resistance and improve treatment efficacy. These advancements are paving the way for personalized therapies tailored to the unique molecular profiles of patients' tumours. Consequently, NCL stands at the forefront of lung cancer management, symbolizing the move towards more precise and individualized oncology care, and marking substantial progress in therapeutic development.

Globally Vibrio cholera antibiotics resistance to RNA and DNA effective antibiotics: A systematic review and meta-analysis.

BACKGROUND: Vibrio cholera (V. cholera) is a facultative pathogen that colonizes the small intestine and produces cholerae toxin as the primary virulence factor that causes cholera and fatal diarrhea in humans. In recent decades, V. cholera has emerged as a notorious multidrug-resistant enteric pathogen. This meta-analysis estimated the pooled proportion of V. cholera antimicrobial resistance against RNA and DNA effective antibiotics. METHOD: A systematic search was performed for relevant literature until 05 June 2021 in PubMed, Scopus, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate weighted pooled resistance (WPR). RESULTS: The meta-analysis were included 164 articles. The WPR of V. cholera were as follows 76% [67,84] to furazolidone, 65% [29,94] to nitrofurantoin, 55% [44,66] to nalidixic acid, 10% [2,23] to rifampicin, 4%(0, 12) to novobiocin, 4% [2,6] to norfloxacin, 3% [1,4] to ciprofloxacin, 1%(0, 3) to sparofloxacin, 0%(0, 3) to levofloxacin, 0%(0, 2) to ofloxacin, 0%(0, 0) to gatifloxacin. CONCLUSION: V. cholera is a severe problem in Asia and Africa, especially in South Asian countries. The resistance patterns are various in geographical regions. novobiocin 0% (0, 0), and ofloxacin 0% (0, 1) in Africa, gatifloxacin 0% (0, 0), and levofloxacin 0% (0, 6) in Asia and ciprofloxacin 0% (0, 2) in North America are most effective antibiotis. The resistance rate to furazolidone, nalidixic acid, nitrofurantoin, and cephalothin has increased over the years. Monitoring antibiotic resistance and prescribing an appropriate antibiotic is vital to control resistance.

Resveratrol supplementation efficiently improves endothelial health: A systematic review and meta-analysis of randomized controlled trials.

We perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to quantify the effect of resveratrol supplementation on endothelial function. A comprehensive search was performed in electronic databases including PubMed, Scopus, Web of Science, and Cochrane Library up to February 2021 with no limitation in time and language. A meta-analysis of eligible studies was performed using a random-effects model to estimate the pooled effect size of flow-mediated dilation (FMD), intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1). In total, 21 arms from 17 studies were included. The meta-analysis results showed that resveratrol significantly change the concentrations of FMD (WMD: 1.43%; 95% CI: 0.98 to 1.88, p < .001) and ICAM-1 (WMD: -7.09 ng/ml, 95% CI: -7.45 to -6.73, p < .001). However, VCAM-1, fibrinogen, and PAI-1 did not change significantly after resveratrol supplementation. In conclusion, the results of this study suggest that resveratrol supplementation can improve endothelial function which could be important, especially in patients with cardiovascular diseases.

The Growth Inhibitory Effect of Resveratrol and Gallic Acid on Prostate Cancer Cell Lines through the Alteration of Oxidative Stress Balance: the Interplay between Nrf2, HO-1, and BACH1 Genes.

BACKGROUND: The association between oxidative stress and prostate cancer (PC) has been demonstrated both epidemiologically and experimentally. Balance in reactive oxygen species (ROS) levels depends on multiple factors, such as the expression of Nrf2, HO-1, and BACH1 genes. Natural polyphenols, such as resveratrol (RSV) and gallic acid (GA), affect cellular oxidative profiles. OBJECTIVE: The present study investigated the possible effects of GA and RSV on the oxidative profiles of PC3 and DU145 cells, as well as Nrf2, HO-1, and BACH1 gene expression to achieve an understanding of the mechanisms involved. METHODS: PC3 and DU145 cells were treated with ascending concentrations of RSV and GA for 72h. Then cell growth and mRNA expression of Nrf2, HO-1, and BACH1 genes were analyzed by real-time PCR. Various spectrophotometric analyses were performed to measure oxidative stress markers. RESULTS: RSV and GA significantly decreased the growth of PC3 and DU145 cells compared to the control group in a concentration-dependent manner. RSV and GA also decreased ROS production in PC3 cells, but in DU145 cells, only the latter polyphenol significantly decreased ROS content. In addition, RSV and GA had ameliorating effects on SOD, GR, GPX, and CAT activities and GSH levels in both cell lines. Also, RSV and GA induced HO- 1 and Nrf2 gene expression in both cell lines. BACH1 gene expression was induced by RSV only at lower concentrations, in contrast to GA in both cell lines. CONCLUSION: Our data suggest that RSV and GA can prevent the growth of prostate cancer cells by disrupting oxidative stress-related pathways, such as changes in Nrf2, HO-1, and BACH1 gene expression.

Icariin, A Novel Promising Complementary Therapeutic Strategy in the Management of Female Infertility: A Literature Review:.

The prevalence of pre-menopausal female infertility is increasing considerably due to various causes such as environmental pollutants, increased administration of chemotherapeutics and radiation exposure, microbial infections, and genetic/epigenetic alterations. However, the current therapeutical strategies remain unfavorite as the disadvantages are strongly challenging. Icariin (ICI) is a phytoestrogen that exerts some promising properties in order to alleviate female infertility. Therefore, the current literature review aimed to evaluate the conducted studies regarding the beneficial impacts of ICI on the female reproductive system and female fecundity. The findings of the present study revealed that ICI is able to modulate the levels of reproductive hormones as it causes a significant decrement in the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) while increasing the levels of estrogen and progesterone. Furthermore, the administration of ICI results in a dramatic alteration in the expression of sex steroids’ receptors, particularly in female reproductive tissues. In addition, preserving ovarian follicular reserve, improving the ovarian and uterine histoarchitecture, elongating the estrous cycle duration, and eventually advancing the female fecundity are other major effects of ICI on the female reproductive system. Despite these desired beneficial properties, the current knowledge appears to be insufficient, hence further investigations, particularly on humans, are encouraged. To the best of our knowledge, this review provides a comprehensive information regarding the beneficial effects of Icariin on female infertility for the firs time.

Designing Effective Multi-Target Drugs and Identifying Biomarkers in Recurrent Pregnancy Loss (RPL) Using In Vivo, In Vitro, and In Silico Approaches.

Recurrent pregnancy loss (RPL) occurs in approximately 5% of women. Despite an abundance of evidence, the molecular mechanism of RPL's pathology remains unclear. Here, we report the protective role of polo-like kinase 1 (PLK1) during RPL. We aimed to construct an RPL network utilizing GEO datasets and identified hub high-traffic genes. We also investigated whether the expressions of PLK1 were altered in the chorionic villi collected from women with RPL compared to those from healthy early pregnant women. Gene expression differences were evaluated using both pathway and gene ontology (GO) analyses. The identified genes were validated using in vivo and in vitro models. Mice with PLK1-overexpression and PLK1-knockdown in vitro models were produced by transfecting certain plasmids and si-RNA, respectively. The apoptosis in the chorionic villi, mitochondrial function, and NF-κB signaling activity was evaluated. To suppress the activation of PLK1, the PLK1 inhibitor BI2536 was administered. The HTR-8/SVneo and JEG-3 cell lines were chosen to establish an RPL model in vitro. The NF-κB signaling, Foxo signaling, PI3K/AKT, and endometrial cancer signaling pathways were identified via the RPL regulatory network. The following genes were identified: PLK1 as hub high-traffic gene and MMP2, MMP9, BAX, MFN1, MFN2, FOXO1, OPA1, COX15, BCL2, DRP1, FIS1, TRAF2, and TOP2A. Clinical samples were examined, and the results demonstrated that RPL patients had tissues with decreased PLK1 expression in comparison to women with normal pregnancies (p < 0.01). In vitro, PLK1 knockdown induced the NF-κB signaling pathway and apoptosis activation while decreasing cell invasion, migration, and proliferation (p < 0.05). Furthermore, the in vivo model proved that cell mitochondrial function and chorionic villi development are both hampered by PLK1 suppression. Our findings revealed that the PLK1/TRAF2/NF-κB axis plays a crucial role in RPL-induced chorionic villi dysfunction by regulating mitochondrial dynamics and apoptosis and might be a potential therapeutic target in the clinic.

Pregnancy outcomes among pregnant women infected with COVID-19 with and without underlying disease: A case-control study.

Emerging infections have many effects on the health of pregnant mothers and their fetuses. Given the importance of coronavirus disease (COVID-19) during pregnancy, this study aims to evaluate the pregnancy and fetal outcomes in pregnant women with COVID-19 by using previous studies. To conduct this study, all studies related to the subject under discussion during the years 2000-2021 were checked out by systematic search in internationally available databases, including Web of Science, Science Direct, Scopus, PubMed, and Google Scholar. Finally, 21 closely related studies were selected to investigate the main objective. The results showed that common symptoms of COVID-19 in pregnant women included fever, cough, and muscle aches. The most common laboratory results included decreased blood lymphocytes and increased blood CRP. Consequences of pregnancy and childbirth in pregnant women included increased preterm delivery and increased cesarean section. Based on the results of the reviewed study, it can be concluded that newborns of mothers with COVID-19 were negative for COVID-19. However, the most common outcome for infants born to mothers with COVID-19 was low birth weight. Clinical signs, laboratory results, and radiographic criteria in pregnant women with COVID-19 are similar to those in non-infected adults. However, it is recommended that precautions be taken to prevent transmission of the virus, as well as preventive health instructions, particularly masking.

Mesenchymal Stem Cells as A New Approach for the Treatment of Multiple Sclerosis:A Literature Review :.

Multiple sclerosis (MS) is a high-prevalence autoimmune and neurodegenerative disease that affects young adults. An ideal treatment for MS should have two characteristics. First, its immunosuppression and immunomodulation effects reduce the abnormal immune response, and second, it improves repair by enhancing intrinsic repair processes or even cell replacement. Most available therapies have the first characteristic. Recent studies have proposed mesenchymal stem cells (MSCs) as a new therapeutic candidate for MS. Different clinical trials and animal models of MS have shown the therapeutic effect of MSCs. In the current study, we reviewed the therapeutic effects of MSCs in the animal model and patients with MS.

Ellagic acid effects on testis, sex hormones, oxidative stress, and apoptosis in the relative sterility rat model following busulfan administration.

BACKGROUND: Busulfan is an antineoplastic medication that is broadly utilized for cancer treatment. It affects the testicular function and leads to sterility. The present study aimed to evaluate the effects of ellagic acid on testicular tissue changes, sexual hormones, antioxidant defense system, and caspase-9 and Bcl2 gene expression in the busulfan-induced relative sterile rat model. METHODS: This is an interventional-experimental animal study that was performed on 65 Adult male rats; they were randomly divided into five groups including control (1 ml of 0.9% normal saline), ellagic acid (50 mg/kg); busulfan (10 mg/kg); and busulfan plus ellagic acid (10 mg/kg and 50 mg/kg). At the end of the experiment, blood samples were collected, and plasma levels of sex hormones, antioxidant system, apoptosis-related genes, and testis histology were assessed. RESULTS: Busulfan reduced the levels of serum testosterone, total antioxidant capacity, gene expression of Bcl2, testicular volume, seminiferous tubule, germinal epithelium, interstitial tissue volume, and the number of spermatogonia, spermatocyte, round spermatid, elongated spermatid, Sertoli cells and Leydig cells (p < 0.05). Busulfan administration resulted in a significant increase (p < 0.05) in the level of LH, FSH, malondialdehyde, and caspase 9. Busulfan + ellagic acid (50 mg/kg) showed higher serum levels of testosterone, gene expression of Bcl-2 and antioxidant markers, and lower LH, FSH levels, and gene expression of caspase 9 compared to the Busulfan-treated rats (p < 0.05). Stereological parameters were also ameliorated in the group treated with Busulfan+ 50 mg/kg ellagic acid (p < 0.05). CONCLUSION: In conclusion, the consumption of ellagic acid may have beneficial effects on the antioxidant defense system, sexual hormone abnormality, and testicular tissue damage induced by busulfan.

Potential anti-inflammatory effect of anti-HMGB1 in animal models of ICH by downregulating the TLR4 signaling pathway and regulating the inflammatory cytokines along with increasing HO1 and NRF2.

Intracerebral hemorrhage (ICH) is a severe clinical problem without effective treatment; the leading cause is neuroinflammation. High-mobility group box one protein (HMGB1) is an abundant protein in the cell nucleus of most mammalian cells, which exerts its function by binding to chromatin. The present study focused on the therapeutic effect of anti-HMGB1 on ICH via the downregulation of inflammatory pathways. The ICH mice models were created by collagenase IV injection in the striatum of mice. Then, mice were received different medications and divided into three groups: anti-HMGB1, anti-Toll-like receptor 4 (TLR4), and non-treated ICH groups. Cerebrospinal fluid (CSF) was obtained, and ELISA was carried out to determine the levels of inflammatory agents. Microglial cells were isolated from the cerebral hemispheres, and then Real-Time PCR and western blot were performed. The results showed that the anti-inflammatory effects of anti-HMGB1 were tremendous than anti-TLR4. Overall, the results showed that anti-HMGB1 had a more reducer effect on pro-inflammatory cytokines release (****P < 0.0001) and expression (****P < 0.0001) than anti-TLR4 when compared with the control group. It was also determined that anti-HMGB1 increased heme-oxygenase-1 (HO1) and nuclear factor erythroid-derived factor 2-related factor 2 (NRF2) (****P < 0.0001) expression in comparison with the control group while it was not significant for anti-TLR4 (CLI-095). The present study suggested that anti-HMGB1 serves as a potential anti-inflammatory molecule via reducing TLR4-related signaling pathways, pro-inflammatory cytokines production, and increasing the production of the anti-inflammatory cytokine along with heme-oxygenase-1 HO1 and NRF2 increment.

Effects of Melatonin and Propolis Supplementation on Inflammation, Oxidative Stress, and Clinical Outcomes in Patients with Primary Pneumosepsis: A Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVE: The present study aimed to investigate the effects of propolis and melatonin supplementation on inflammation, clinical outcomes, and oxidative stress markers in patients with primary pneumosepsis. MATERIALS AND METHODS: This pilot randomized controlled trial was conducted on 55 patients with primary pneumosepsis who were randomly assigned to the intervention and control groups. In the three intervention groups, the patients received propolis alone (1,000 mg/day), propolis (1,000 mg/day) plus melatonin (20 mg/day), and melatonin alone (20 mg/day). The control group received placebo. The inflammatory and oxidative stress markers as well as clinical outcomes were evaluated before and after the intervention, and the 28-day survival rate was also recorded. RESULTS: After the intervention, the combination of propolis and melatonin significantly reduced interleukin-6 (-55.282 pg/mL) and C-reactive protein (-21.656 mg/L) levels, while increasing gavage intake (326.680 mL/day) and improving some clinical outcomes (APACHE II, SOFA, and NUTRIC scores) compared to the control group. However, no significant difference was observed between the groups in terms of oxidative stress and hematological indices. In addition, there was no significant difference in the 28-day survival rate between the groups (p = 0.07). CONCLUSION: Supplementation with propolis and melatonin may improve clinical outcomes by reducing inflammation. Further investigations are required to confirm these findings.