Recent advances in non-small cell lung cancer targeted therapy; an update review.

Lung cancer continues to be the leading cause of cancer-related death worldwide. In the last decade, significant advancements in the diagnosis and treatment of lung cancer, particularly NSCLC, have been achieved with the help of molecular translational research. Among the hopeful breakthroughs in therapeutic approaches, advances in targeted therapy have brought the most successful outcomes in NSCLC treatment. In targeted therapy, antagonists target the specific genes, proteins, or the microenvironment of tumors supporting cancer growth and survival. Indeed, cancer can be managed by blocking the target genes related to tumor cell progression without causing noticeable damage to normal cells. Currently, efforts have been focused on improving the targeted therapy aspects regarding the encouraging outcomes in cancer treatment and the quality of life of patients. Treatment with targeted therapy for NSCLC is changing rapidly due to the pace of scientific research. Accordingly, this updated study aimed to discuss the tumor target antigens comprehensively and targeted therapy-related agents in NSCLC. The current study also summarized the available clinical trial studies for NSCLC patients.

Immunogenicity of COVID-19 vaccines in adult patients with autoimmune inflammatory rheumatic diseases: A systematic review and meta-analysis.

COVID-19 vaccines approved by the Food and Drug Administration have been studied mainly in healthy individuals and there is limited information on their immunogenicity in patients with autoimmune diseases. Therefore, the current systematic review and meta-analysis study, aimed to comprehensively investigate the immunogenicity of these vaccines in patients with autoimmune inflammatory rheumatoid diseases (AIRDs). A comprehensive literature search was performed on various databases, including Google Scholar, PubMed, Web of Science, EMBASE, and Cochrane Library, to select cohort and randomized clinical trial (RCT) studies up to January 2022. Also, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist protocol and the I2 statistic were used for quality assessment and heterogeneity tests of the selected studies. Fixed and random-effects models were estimated based on the heterogeneity tests, and pooled data were determined as the ratio of mean (ROM) with a 95% confidence interval (CI). As a result, we found that vaccines can cause favorable immunogenicity and antibody response in vaccinated AIRD patients; however, older age and the concomitant consumption of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs) could significantly reduce the vaccine immunogenicity. Consequently, our findings revealed significant humoral responses (seropositive) in AIRD patients following the administration of COVID-19 vaccines.

The effects of methotrexate on the immune responses to the COVID-19 vaccines in the patients with immune-mediated inflammatory disease: A systematic review of clinical evidence.

COVID-19 vaccines exhibit high levels of immunogenicity in the overall population. Data on the effects of immunomodulators on the consequences of COVID-19 in patients with Immune-mediated inflammatory diseases (IMIDs) remains scarce. This systematic review aimed to evaluate the immune responses to the COVID-19 vaccines in IMID patients receiving methotrexate (MTX) compared to healthy individuals. A comprehensive literature search was carried out using electronic databases such as PubMed, Web of Science, Scopus, Google Scholar, and Embase up to August 2022 to identify eligible RCTs evaluating the effect of MTX on immune responses in patients with COVID-19. The PRISMA checklist protocol was applied for the quality assessment of the selected trials. Our findings demonstrated that MTX lowered the responses of T cells and antibodies in IMID patients compared to healthy controls. We also discovered that young age (<60 years) was the main parameter influencing the antibody response after vaccination, while MTX had little effect. Following vaccination, MTX-hold and age were considered the main factors influencing the antibody response. In patients older than 60 years of age, the time point of 10 days of MTX discontinuation was critical to boosting the humoral response to anti-SARS-CoV-2 IgG. Because many IMID patients did not have adequate humoral and cellular responses, our findings highlighted the importance of second or booster doses of vaccine and temporary MTX discontinuation. As a result, it implies that individuals with IMIDs should be subjected to more research, particularly humoral and cellular immunity efficiency trials after COVID-19 vaccination, until credible information is achieved.

The effect of anthocyanins supplementation on liver enzymes: A systematic review and meta-analysis of randomized clinical trials.

This systematic review and meta-analysis aimed to assess effect of consuming anthocyanins (ACNs; pure ACNs or products containing ACNs) on liver enzymes levels including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT). Although no significant impact was detected on the liver enzymes, a significant reduction was observed on ALT (WMD = -4.932 U/L, 95% CI = -9.848 to -0.015, p = .049) and AST (WMD = -3.464 U/L, 95% CI = -6.034 to -0.894, p = .008) in the studies that examined them as primary outcomes. A significant decrease was found on AST among the healthy subjects (WMD = -4.325 U/L, 95% CI = -8.516 to -0.134, p = .043) and in the studies that used products containing ACNs as intervention (WMD = -2.201 U/L, 95% CI = -4.275 to -0.127, p = .037). Although no significant relation was detected between ACNs dosage and the liver enzymes, significant associations were found between the duration of trial with ALT (ALT: slope: 0.09, 95% CI = 0.040 to 0.139, p = .0003) and AST (slope: 0.076, 95% CI = 0.037 to 0.115, p = .0001). In conclusion, although ACNs had no significant effect on the liver enzymes, a significant decrease was discovered on ALT and AST in the studies that evaluated them as primary outcomes. A significant reduction was observed in AST in the healthy individuals and in the studies used products containing ACNs as intervention. Significant relations were also found between the duration of trial with ALT and AST. Further studies are required to confirm these results.

The effect of grape products containing polyphenols on oxidative stress: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The literature showed that Grape Products Containing Polyphenols (GPCP) had anti-oxidant activity. However, the effects of GPCP on different biomarkers of oxidative stress are still controversial. In this regard, this systematic review and meta-analysis aimed to evaluate the effect of Grape Products Containing Polyphenols (GPCP) intake on oxidative stress markers. METHODS: PubMed, Scopus, Web of Science, and Google Scholar data bases were searched up to August 20, 2020. A random-effects model, weighted mean difference (WMD), and 95% confidence interval (CI) were applied for data analysis. Meta-analysis was conducted over 17 eligible RCTs with a total of 633 participants. The study registration number is CRD42019116696. RESULTS: A significant increase was observed in Total Antioxidant Capacity (TAC) (weighted mean difference (WMD) = 1.524 mmol/L, 95% confidence interval (CI): 0.83, 2.21). Intake of GPCP enhanced Superoxide Dismutase (SOD) (WMD = 0.450 mmol/L, 95% CI: 0.23, 0.66), TAC (WMD = 2.829 mmol/L, 95% CI: 0.13, 5.52), and Oxygen Radical Absorbance Capacity (ORAC) (WMD = 0.524 µmol/L, 95% CI: 0.42, 0.62) among healthy participants. Higher GPCP doses increased SOD (WMD = 0.539 U/mgHb, 95% CI: 0.24, 0.82) and ORAC (WMD = 0.377 µmol/L, 95% CI: 0.08, 0.67), whereas longer intervention periods enhanced ORAC (WMD = 0.543 µmol/L, 95% CI: 0.43, 0.64). CONCLUSION: GPCP intake may partly improve status of oxidative stress, but further well-designed trials are required to confirm these results.

The effect of grape products containing polyphenols on C-reactive protein levels: a systematic review and meta-analysis of randomised controlled trials.

Although grape polyphenols can decrease chronic inflammations, their effect on C-reactive protein (CRP) levels is still controversial. So, this meta-analysis was conducted to investigate the effect of grape products containing polyphenols on CRP concentrations. In order to collect the relevant randomised controlled trials (RCT), the databases of PubMed, Scopus, Web of Science and Google Scholar were searched up to 30 March 2020. The random effects model, standardised mean difference (SMD) and 95 % CI were applied in data analysis. Meta-analysis was conducted over seventeen eligible RCT containing a total of 668 participants. The study registration number is CRD42018110169. Based on the results, grape products containing polyphenols decreased CRP levels significantly (SMD = −0·229; 95 % CI −0·41, −0·05; P = 0·013). Sensitivity analysis was performed by removing each individual study and the results did not change. According to the subgroup analysis, higher doses of grape polyphenols (>500 mg/d) and longer intervention periods (≥12 weeks) had significant effects on CRP levels. Furthermore, grape polyphenols significantly reduced the CRP levels in patients with a clinical condition. In the same vein, grape seed extract and other grape products, such as grape extract, juice and raisins, decreased CRP levels significantly. According to the meta-regression results, the CRP level depends on the dose and duration of the grape polyphenol supplementation. Based on the findings, grape products containing polyphenols had a significant effect on CRP levels. Further well-designed and long-term clinical trials are highly recommended to achieve more comprehensive and accurate results.

A Study on Association Between Protein Carbonyl and Anti-cyclic Citrullinated Peptide Antibody in Rheumatoid Arthritis: Introducing a New Supplementary Biomarker.

Redox state and immune mechanisms are two major factors implicated in rheumatoid arthritis (RA). Regarding some limitations of anti-cyclic citrullinated peptide (anti-CCP) antibody in RA diagnosis, recruiting another strong marker of oxidative stress could lead to more definitive diagnosis. To evaluate the potential of protein carbonyl content as a supplementary biomarker for RA. Eighty patients with RA attending the Research Center from 2015 to 2016 were recruited in this study. Smoker and alcoholic subjects, or those with any other systemic illness were excluded from the study. Demographic information and clinical data were collected. Numbers of swollen and tender joints were determined and RA disease activity was assessed. Serum samples were used for assessing protein carbonyl level, platelet count, and anti-CCP antibody values. Statistical analyses for significant differences were performed according to parametric (Student t test) and nonparametric (Mann-Whitney test) tests. The correlation was determined by Pearson coefficient. There was a significant correlation between protein carbonyl levels and anti-CCP antibodies in active RA (p value = 0.01), but not in remission phase (p value = 0.28). A significant positive correlation was observed between protein carbonyl levels and platelets count in active RA (p value = 0.001), but not in remission phase (p value = 0.85). Protein carbonyl could be considered as a future cost-effective supplementary biomarker, alongside anti-CCP antibody, in active RA diagnosis as it showed a significant positive correlation with anti-CCP antibody and platelet, two major mediators in the disease pathogenesis.

Empirically derived dietary patterns and obesity among Iranian Adults: Yazd Health Study-TAMYZ and Shahedieh cohort study.

The aim was to determine the relationship between dietary patterns derived by principal component analysis (PCA) in association with obesity from a large group of Iranian adults in the urban and suburb areas. A cross-sectional study was conducted on 10,693 Iranian adults. The data were collected from two cohort studies: Shahedieh city annexed to Yazd area as well as Yazd Health Study (YaHS)-TAMYZ (Yazd Nutrition Survey in Persian) in urban area. Dietary intakes were assessed using a validated semi-quantitative food frequency questionnaire. The PCA was applied to identify the dietary patterns. Multiple logistic regressions were run to assess the relationship between dietary patterns and obesity. In Shahedieh cohort study, three major dietary patterns were identified traditional, unhealthy, and prudent pattern. Prudent pattern was associated with lower odds of obesity (OR: 0.68; 95% CI: 0.53, 0.88). Higher adherence to the unhealthy (OR: 1.24; 95% CI: 1.02, 1.50) and traditional (OR: 1.38; 95% CI: 1.11, 1.72) patterns was related to greater odds of obesity. Moreover, we identified traditional and unhealthy dietary patterns in YaHS study. Higher adherence to the unhealthy dietary pattern was associated with greater odds of obesity (OR: 1.21 95% CI: 1.02, 1.44). Greater adherence to unhealthy dietary patterns was associated with higher odds of obesity in participants. Greater adherence to traditional and prudent dietary patterns increased and decreased the obesity odds, respectively. Further prospective studies are needed to find out the causal relationship between the variables.

The immunomodulatory effects of tachykinins and their receptors.

Tachykinins (TKs) are a family of neuropeptides mainly expressed by neuronal and non-neuronal cell types, especially immune cells. Expression of TKs receptors on immune cell surfaces, their involvement in immune-related disorders, and therefore, understanding their immunomodulatory roles have become of particular interest to researchers. In fact, the precise understanding of TKs intervention in the immune system would help to design novel therapeutic approaches for patients suffering from immune disorders. The present review summarizes studies on TKs function as modulators of the immune system by reviewing their roles in generation, activation, development, and migration of immune cells. Also, it discusses TKs involvement in three main cellular mechanisms including inflammation, apoptosis, and proliferation.

Serum hepcidin level and rheumatoid arthritis disease activity.

OBJECTIVE: The present study aimed to determine the relationship between the serum hepcidin level and disease activity in patients with rheumatoid arthritis (RA). METHODS: This study was conducted on 80 patients with RA (36 cases with anemia of chronic disease [ACD] and 44 patients without ACD). Disease activity was measured by the 28-joint Disease Activity Score based on the erythrocyte sedimentation rate (DAS28-ESR). According to the DAS28-ESR score, 52 and 28 cases were categorized as inactive to moderately active RA (DAS28-ESR≤5.1) and highly active RA (DAS28-ESR>5.1), respectively. In addition, the serum hepcidin level was evaluated in all patients to determine its correlation with the DAS28-ESR score. RESULTS: There was no significant difference between the RA with ACD and RA without ACD groups in terms of the median (interquartile range) hepcidin level (1207 [985.2] vs. 923.8 [677.3] ng/mL; P=0.57). Likewise, no significant difference was observed between the active RA and inactive to moderately active RA groups in this regard (1131.8 [991.3] vs. 1090.9 [631.4] ng/mL; P=0.53). CONCLUSION: Hepcidin has no association with disease activity in RA. Therefore, it is not necessary to measure hepcidin to determine the RA activity.

Amelioration of regulatory T cells by Lactobacillus delbrueckii and Lactobacillus rhamnosus in pristane-induced lupus mice model.

Regulatory T cells (Tregs) play an indispensable role in the control of immune responses and induction of peripheral tolerance. Dysregulation of Tregs is involved in the pathogenesis of systemic lupus erythematosus (SLE). Tolerogenic probiotics have shown beneficial effects in the control of autoimmune diseases. We evaluated the prophylactic and therapeutic effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on Tregs and their related molecules in pristane-induced lupus mice model. Fifty-four female BALB/c mice (3-5 weeks) were randomly divided into nine groups. Lupus was induced in all groups using pristane. Prophylactic groups were treated from Day 0 (at the time of pristane injection) and treatment groups were treated 2 months later with L. rhamnosus, L. delbrueckii, mix of both probiotics, and prednisolone. One group was considered as SLE-induced control group without any treatment. Presence of antinuclear antibodies (ANA), antidouble-stranded DNA (anti-dsDNA), antiribonucleoprotein (anti-RNP), proteinuria, and serum level of creatinine, urea, the expression of forkhead box P3 (Foxp3), interleukin 6 (IL-6), IL-10, transforming growth factor ß, and the number of Tregs were determined. SLE induction by pristane led to the formation of lipogranuloma, presence of ANA, anti-dsDNA, and anti-RNP. Probiotics consumption decreased the level of lipogranuloma, ANA, and anti-dsDNA. In addition, in probiotics receiving groups, Tregs and the expression level of Foxp3 increased, while IL-6 decreased. The effect of probiotics in the prophylactic group was more prominent. The results may indicate the effectiveness of L. delbrueckii and L. rhamnosus in the enhancement of Tregs and the decrease of inflammatory cytokines and disease severity in SLE-induced mice.

In vivo study: Th1-Th17 reduction in pristane-induced systemic lupus erythematosus mice after treatment with tolerogenic Lactobacillus probiotics.

Uncontrolled inflammation in systemic lupus erythematosus (SLE) could cause dysfunction in multiple organs. T helper 17 (Th17) cells are a main branch of inflammatory responses in the pathogenesis of SLE, and by producing interleukin 17 (IL-17), represent a major functional tool in the progression of inflammation. Animal models provide a special field for better studies of the pathogenesis of diseases. Tolergenic probiotics could decrease inflammation in autoimmune diseases by modulating the immune system and maintaining homeostasis. The aim of this project was to evaluate the effects of Lactobacillus rhamnosus and Lactobacillus delbrueckii on Th17 cells and their related mediators in a pristane-induced BALB/c mice model of SLE. The mice were divided into pretreatment groups, which received probiotics or prednisolone at Day 0, and treatment groups, which received probiotics and prednisolone 2 months after injection. The presence of antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and anti-ribonucleoprotein (anti-RNP) and lipogranuloma was evaluated; also, the population of Th1-Th17 cells as well as interferon Î³ (IFN-γ), IL-17, and IL-10 levels, and the expression of RAR-related orphan related receptor gamma (RORγt) and IL-17 were determined. We observed that probiotics and prednisolone could delay SLE in pretreatment and treatment mice groups, with a reduction in ANA, anti-dsDNA, anti-RNP, and mass of lipogranuloma. Probiotics and prednisolone decreased the population of Th1-Th17 cells and reduced IFN-γ and IL-17 as inflammatory cytokines in the pretreatment and treatment groups in comparison with SLE-induced mice. Our results indicated that, due to their anti-inflammatory properties and reduction of Th17, Th1, and cytotoxic T lymphocyte (CTL) cells, the use of these probiotics could probably represent a new tool for the better management of SLE.