Integrated bioinformatics approaches and expression assays identified new markers in pituitary adenomas.

Pituitary adenomas (PA) include about one third of primary central nervous tumors in adolescent and young adult. Despite extensive research, the underlying mechanism of PA tumorigenesis is still unknown. In the present study, through bioinformatics analysis of a PA-related dataset downloaded from GEO database, we attempted to identify pair(s) of lncRNA/target mRNA whose expression changes may be involved in the tumorigenesis of PAs. For this end, we evaluated expression of a set of bioinformatically obtained genes in 46 PA tissues against adjacent non-tumor pituitary tissues. The bioinformatics step led to selection of four genes for validation through expression assays. Expression levels of HIF1A and MAPK1 were increased in NFPA tissues (P < 0.0001 and =0.0042, respectively). Expression level of BANCR was significantly decreased in tumor tissues (P < 0.0001). However, expression of STAT3 was not meaningfully different between the two tissue types (P = 0.56). Since there was no significant correlation between MAPK1 and BANCR expressions in either tumor or adjacent normal tissues, the regulatory effect of BANCR on MAPK1 was not confirmed. In conclusion, this study offers information about deregulation of bioinformatically identified genes in PA tumors and indicates that further studies in this field is needed to understand the involved molecular mechanisms.

KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions.

RAS mutations are among the most common oncogenic mutations in human cancers. Among RAS mutations, KRAS has the highest frequency and is present in almost 30% of non-small-cell lung cancer (NSCLC) patients. Lung cancer is the number one cause of mortality among cancers as a consequence of outrageous aggressiveness and late diagnosis. High mortality rates have been the reason behind numerous investigations and clinical trials to discover proper therapeutic agents targeting KRAS. These approaches include the following: direct KRAS targeting; synthetic lethality partner inhibitors; targeting of KRAS membrane association and associated metabolic rewiring; autophagy inhibitors; downstream inhibitors; and immunotherapies and other immune-modalities such as modulating inflammatory signaling transcription factors (e.g., STAT3). The majority of these have unfortunately encountered limited therapeutic outcomes due to multiple restrictive mechanisms including the presence of co-mutations. In this review we plan to summarize the past and most recent therapies under investigation, along with their therapeutic success rate and potential restrictions. This will provide useful information to improve the design of novel agents for treatment of this deadly disease.

IL-6 and TNF-α responses to acute and regular exercise in adult individuals with multiple sclerosis (MS): a systematic review and meta-analysis.

BACKGROUND: In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls. METHOD: We performed an online search via PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Library till September 2021 to identify original studies on IL-6 and TNF-α changes after acute and regular exercise in PwMS and controls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 original studies were included in the meta-analysis. Sensitivity analyses were used to identify the origins of heterogeneity. R 4.0.4 was used to perform the meta-analysis of IL-6 and TNF-α levels before and after acute and regular exercise in PwMS, compared to controls. This study does not qualify for a clinical trial number. RESULTS: IL-6 levels did neither increase nor decrease after acute and regular exercise in PwMS, and compared to controls (pre- vs. post-intervention: Standardized Mean Difference (SMD) -0.09, 95% CI [-0.29; 0.11], p-value = 0.37, PwMS vs. Control: SMD -0.08, 95% CI [-0.33; 0.16], p-value = 0.47). In PwMS, TNF-α levels decreased after regular exercise and when TNF-α levels of both acute and regular exercise were pooled (pre- vs. post-intervention: SMD -0.51, 95% CI [-0.91; 0.11], p-value = 0.01, PwMS vs. Control: SMD -0.23, 95% CI [-0.66; 0.18], p-value = 0.26). TNF-α levels did neither increase nor decrease after acute and regular exercise in PwMS, when compared to controls. CONCLUSION: This systematic review and meta-analysis show that exercise does not lead to significant changes in peripheral levels of IL-6 in PwMS in contrast to the observed response in healthy subjects and other medical contexts. However, regular exercise had a specific anti-inflammatory effect on blood TNF-α levels in PwMS. It remains to be investigated why PwMS display this different exercise-induced pattern of cytokines.