Inosine, gut microbiota, and cancer immunometabolism.

This article briefly reviews cancer immunity and the role of gut microbiota in carcinogenesis, followed by an understanding of mechanisms by which inosine is involved in cancer immunometabolism. The immune system plays a paradoxical role in cancer treatment. Antitumor immunity depends on the T-cell priming against tumor antigens, whereas inflammatory mediators trigger the protumor signaling in the tumor microenvironment. Studies link the microbiome with metabolism and immunity-two main factors implicated in carcinogenesis. Gut microbiota has been shown to affect both antitumor immunity and protumor immune signaling. There is mounting evidence that the human microbiome can play a role in the immunotherapeutic effects, both response and resistance. Inosine-5'-monophosphate dehydrogenase (IMPDH) is a highly conservative enzyme widely expressed in mammals. Cell signaling pathways use molecular inosine, a crucial secondary metabolite in purine metabolism and a molecular messenger. Recent research has identified inosine as a critical regulator of immune checkpoint inhibition (ICI) therapeutic response in various tumor types. Some bacterial species were found to produce inosine or its metabolite hypoxanthine and induce T-helper 1 differentiation and effector functions via the inosine-A2AR-cAMP-PKA pathway upon ICI therapy. Also, inosine acts as a substitute carbon source for T-cell metabolism in glucose-restricted environments, i.e., the tumor microenvironment, assisting T-cell proliferation and differentiation while enhancing sensitivity to ICI, reinforcing the notion that inosine metabolism might contribute to antitumor immunity. Also, inosine is a potent agonist of the adenosine receptor, A2AR, and A2AR signaling can affect T-cell responses and antitumor immunity, making the inosine-A2AR pathway blockage a candidate for cancer treatment. Further research is required to investigate inosine as a cancer immunometabolism therapy.

BDNF and its signaling in cancer.

PURPOSE: Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophic factors that can potentially increase cancer cell growth, survival, proliferation, anoikis, and migration by tyrosine kinase receptors TrkB and the p75NTR death receptor. The activation of BDNF/TrkB pathways leads to several downstream signaling pathways, including PI3K/Akt, Jak/STAT, PLCγ, Ras-Raf-MEK-ERK, NF-kB, and transactivation of EGFR. The current review aimed to provide an overview of the role of BDNF and its signaling in cancer. METHODS: We searched a major medical database, PubMed, to identify eligible studies for a narrative synthesis. RESULTS: Pathological examinations demonstrate BDNF overexpression in human cancer, notably involving the prostate, lung, breast, and underlying tissues, associated with a higher death rate and poor prognosis. Therefore, measurement of BDNF, either for identifying the disease or predicting response to therapy, can be helpful in cancer patients. Expression profiling studies have recognized the role of microRNAs (miR) in modulating BDNF/TrkB pathways, such as miR-101, miR-107, miR-134, miR-147, miR-191, miR-200a/c, miR-204, miR-206, miR-210, miR-214, miR-382, miR-496, miR-497, miR-744, and miR-10a-5p, providing a potential biological mechanism by which targeted therapies may correlate with decreased BDNF expression in cancers. Clinical studies investigating the use of agents targeting BDNF receptors and related signaling pathways and interfering with the related oncogenic effect, including Entrectinib, Larotrectinib, Cabozantinib, Repotrectinib, Lestaurtinib, and Selitrectinib, are in progress. CONCLUSION: The aberrant signaling of BDNF is implicated in various cancers. Well-designed clinical trials are needed to clarify the BDNF role in cancer progression and target it as a therapeutic method.

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19.

Natural resources have long played a prominent part in conventional treatments as a parental source due to their multifaceted functions and lesser side effects. The diversity of marine products is a significant source of possible bioactive chemical compounds with a wide range of potential medicinal applications. Marine organisms produce natural compounds and new drugs with unique properties are produced from these compounds. A lot of bioactive compounds with medicinal properties are extracted from marine invertebrates, including Peptides, Alkaloids, Terpenoids, Steroids. Thus, it can be concluded that marine ecosystems are endowed with natural resources that have a wide range of medicinal properties, and it is important to examine the therapeutic and pharmacological capabilities of these molecules. So, finding particular inhibitors of the COVID-19 in natural compounds will be extremely important. Natural ingredients, in this light, could be a valuable resource in the progression of COVID-19 therapeutic options. Controlling the immunological response in COVID-19 patients may be possible by addressing the PI3K/Akt pathway and regulating T cell responses. T cell effector activity can be improved by preventing anti-viral exhaustion by suppressing PI3K and Akt during the early anti-viral response. The diversity of marine life is a significant supply of potentially bioactive chemical compounds with a broad range of medicinal uses. In this study, some biologically active compounds from marine organisms capable of inhibiting PI3K/AKT and the possible therapeutic targets from these compounds in viral infection COVID-19 have been addressed.

Anti-SARS-CoV-2 spike IgG following injection of the third dose vaccine: A systematic review with meta-analysis of heterologous versus homologous vaccination.

Background: The mass vaccination is a key strategy to prevent and control the coronavirus disease 2019 (COVID-19) pandemic. Today, several different types of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed worldwide. These vaccines are usually administered in a two-dose schedule, and the third dose is currently being administered in most countries. This study aimed to systematically review and meta-analyze the immunogenicity of heterologous vs. homologous vaccination after administration of the third dose of COVID-19 vaccines. Methods: Electronic databases and websites including Scopus, PubMed, Web of Science, and Google scholar were searched for relevant randomized clinical trial (RCT) studies. After applying the inclusion and exclusion criteria, a total of three RCTs were included in the study. These RCTs were included 2,613 healthy adults (18 years or older and without a history of laboratory-confirmed COVID-19) with 15 heterologous and five homologous prime-boost vaccination regimens. Anti-SARS-CoV-2-spike IgG levels at day 28 after administration of the third dose, were compared between the heterologous and homologous regimens. Results: The highest antibody responses had been reported for the homologous vaccination regimen of m1273/m1273/m1273 (Moderna), followed by the heterologous regimen of BNT/BNT/m1273. In addition, the immunogenicity of viral vector and inactivated vaccines was remarkably enhanced when they had been boosted by a heterologous vaccine, especially mRNA vaccines. Conclusion: This systematic review suggests that mRNA vaccines in a homologous regimen induce strong antibody responses to SARS-CoV-2 compared to other vaccine platforms. In contrast, viral vector and inactivated vaccines show a satisfactory immunogenicity in a heterologous regimen, especially in combination with mRNA vaccines.

How Prevalent Is Cancer in Confirmed Cases with Coronaviruses and Severe Acute Respiratory Syndromes?

Novel coronavirus disease 2019 (COVID-19) has posed a crucial hazard to global health. The new species share similarities with the two previously emerged entities: severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) that have caused outbreaks in 2002 and 2012, respectively. Interestingly, all of these coronaviruses can cause potentially fatal respiratory syndromes, though behave differently in patients with cancer compared to patients without cancer. Accordingly, the present chapter aims to, through a systematic investigation, estimate the prevalence of cancer among COVID-19, SARS, and MERS confirmed cases. Our analysis based on data from 78 studies with SARS, MERS, and COVID-19 confirmed cases showed that the prevalence of cancer (4.94%) stands at fourth place after hypertension (20.8%), diabetes (11.39%), and cardiovascular diseases (7.46%). According to the findings of the present study, comorbidities are significantly more common in patients with MERS compared to patients with COVID-19 and SARS, and this was the cancer case as well. Further studies need to address whether or not patients with coronaviruses and cancer are different from patients with coronaviruses without cancer in terms of clinical manifestations, laboratory findings, outcomes, and men to women ratio.

The Potential Diagnostic and Prognostic Value of Circulating MicroRNAs in the Assessment of Patients With Prostate Cancer: Rational and Progress.

Prostate cancer (P.C.) is one of the most frequent diagnosed cancers among men and the first leading cause of death with an annual incidence of 1.4 million worldwide. Prostate-specific antigen is being used for screening/diagnosis of prostate disease, although it is associated with several limitations. Thus, identification of novel biomarkers is warranted for diagnosis of patients at earlier stages. MicroRNAs (miRNAs) are recently being emerged as potential biomarkers. It has been shown that these small molecules can be circulated in body fluids and prognosticate the risk of developing P.C. Several miRNAs, including MiR-20a, MiR-21, miR-375, miR-378, and miR-141, have been proposed to be expressed in prostate cancer. This review summarizes the current knowledge about possible molecular mechanisms and potential application of tissue specific and circulating microRNAs as diagnosis, prognosis, and therapeutic targets in prostate cancer.

Prevalence of physical inactivity in Iran: a systematic review.

Introduction: Physical inactivity is one of the most important risk factors for chronic diseases, including cardiovascular disease, cancer, and stroke. We aim to conduct a systematic review of the prevalence of physical inactivity in Iran. Methods: We searched international databases; ISI, PubMed/Medline, Scopus, and national databases Irandoc, Barakat knowledge network system, and Scientific Information Database (SID). We collected data for outcome measures of prevalence of physical inactivity by sex, age, province, and year. Quality assessment and data extraction has been conducted independently by two independent research experts. There were no limitations for time and language. Results: We analyzed data for prevalence of physical inactivity in Iranian population. According to our search strategy we found 254 records; of them 185 were from international databases and the remaining 69 were obtained from national databases after refining the data, 34 articles that met eligible criteria remained for data extraction. From them respectively; 9, 20, 2 and 3 studies were at national, provincial, regional and local levels. The estimates for inactivity ranged from approximately 30% to almost 70% and had considerable variation between sexes and studied sub-groups. Conclusion: In Iran, most of studies reported high prevalence of physical inactivity. Our findings reveal a heterogeneity of reported values, often from differences in study design, measurement tools and methods, different target groups and sub-population sampling. These data do not provide the possibility of aggregation of data for a comprehensive inference.

Communication Barriers Perceived by Nurses and Patients.

Communication, as a key element in providing high-quality health care services, leads to patient satisfaction and health. The present Cross sectional, descriptive analytic study was conducted on 70 nurses and 50 patients in two hospitals affiliated to Alborz University of Medical Sciences, in 2012. Two separate questionnaires were used for nurses and patients, and the reliability and validity of the questionnaires were assessed. In both groups of nurses and patients, nurse-related factors (mean scores of 2.45 and 2.15, respectively) and common factors between nurses and patients (mean scores of 1.85 and 1.96, respectively) were considered the most and least significant factors, respectively. Also, a significant difference was observed between the mean scores of nurses and patients regarding patient-related (p=0.001), nurse-related (p=0.012), and environmental factors (p=0.019). Despite the attention of nurses and patients to communication, there are some barriers, which can be removed through raising the awareness of nurses and patients along with creating a desirable environment. We recommend that nurses be effectively trained in communication skills and be encouraged by constant monitoring of the obtained skills.

Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus.

Stress predisposes the brain to various neuropathological disorders. Fibrates like gemfibrozil, commonly used for hyperlipidemia, have not yet been examined for their protective/deteriorative potential against restraint stress-induced disturbances. Pretreatment of rats with a range of gemfibrozil concentrations showed significant protection against stress consequences at 90 mg/kg of gemfibrozil, as it resulted in the highest level of antioxidant defense system potentiation among other doses. It also reduced plasma corticosterone compared with the stressed animals. Administration of gemfibrozil (90 mg/kg) before stress induction was able to significantly induce the protein levels of some protective factors including hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in the antioxidant nuclear factor erythroid-derived 2-like 2 (Nrf-2) pathway, as well as mitochondrial pro-survival proteins, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1). In parallel, the level of cleaved caspase-3 and apoptosis-inducing factor (AIF), two proteins involved in apoptotic cell death, and the number of damaged neurons detected in hematoxylin-eosin (H&E) stained hippocampus sections were suppressed in the presence of gemfibrozil. Herein, although gemfibrozil demonstrated protection against the restraint stress, considering its dose and context-dependent effects reported in the previous studies, as well as its common application in clinic, further investigations are essential to unravel its exact beneficial/deleterious effects in various neuronal contexts.