Alleviative effects of green-fabricated zinc oxide nanoparticles on acrylamide-induced oxidative and inflammatory reactions in the rat stomach via modulating gastric neuroactive substances and the MiR-27a-5p/ROS/NF-κB axis.

Little is known about the effects of acrylamide (AMD) on the stomach. So, this study evaluated the effect of oral AMD exposure (20 mg/kg b.wt) on oxidative status, apoptotic, and inflammatory reactions in rat's stomach for 60 days. To explore novel targets of AMD toxicity, a more detailed molecular and immune-expression study was performed. Besides, the possible protective effect of green synthesized zinc oxide nanoparticles (G-ZNP) (10 mg/kg b.wt) was explored. The results revealed that AMD significantly provoked oxidative and lipid peroxidative damage of the stomach in terms of increased ROS and MDA but reduced SOD, CAT, GSH, and GSH/GSSG. Additionally, the stomachs of AMD-exposed rats showed a significant increment of PGE2 but reduced NO. Histopathologically, AMD induced a significant increase in PAS stain and the immunoexpression of iNOS and NF-κB in the glandular stomach. A significant upregulation of CART, VACHT, EGFR, caspase-3, NOS-1, and miR-27a-5p was evident in the stomach of the AMD group. Yet, G-ZNP oral dosing significantly rescued the AMD-induced oxidative damage, apoptotic reaction, inflammatory effect, and altered miR-27a-5p and gene expressions in the stomach. Conclusively, these findings demonstrated the efficacy of G-ZNP in protecting against the harmful impacts of acrylamide on stomach tissues.

Exploring the therapeutic potential of Pongamia pinnata plant extract against skin cancer: In-silico and in-vitro study.

ETHNOPHARMACOLOGICAL RELEVANCE: Pongamia pinnata Linn belonging to the Fabaceae family, holds significance as a crucial remedy in herbal medicine. AIM OF THE STUDY: The present study aims to determine the anticancer and antioxidant properties of the plant extract. MATERIAL AND METHODS: The methodology includes extraction of the leaf sample by soxhlet method followed by the phytochemical analysis of leaf extract. Through in-silico approach three anti-cancer receptors were analyzed with 10 ligands which were studied using molecular docking and molecular simulation approach. The prediction outcome of in-silico tests on the petroleum ether plant extract served as a foundation for the subsequent in-vitro studies. Phytochemical profiling of plant extracts using GC-MS analysis, and cytotoxicity testing for A431 skin cell line using MTT Assay. RESULTS: The binding affinity of Pongamia pinnata as an anti-cancer agent with respect to the targets EGF, EGFR, ERBB2 was evident. In the in-silico studies, the highest binding affinity with respect to the docked complexes were -8.2 kcal/mol for EGF with Pazopanib, -8.3 kcal/mol for EGFR with pongachromene, -9.5 kcal/mol for ERBB2 with Vitexin. Further these complexes were assessed by molecular simulations and it confirms the stability of these complexes. In in-vitro studies the HPLC results indicated the presence of 0.176 ± 0.001 mg/mL of phenols and 0.159 ± 0.001 mg/mL of flavonoids. The IC50 value was 1.051 which revealed the antioxidant potential. The cytotoxicity studies against the A431 skin cancer cell resulted in an IC50 concentration of 89.59 µg/ml. CONCLUSIONS: These studies show that P. pinnata has the properties to serve as a therapeutic agent for the treatment of skin tumors. The molecular simulation studies approach is a predictor for drug discovery, acting as a basis for testing anti-cancer activity against the skin tumor. As a result, it can be a useful source of crude drug for the treatment of melanomas.

Synthesis and biological research of new imidazolone-sulphonamide-pyrimidine hybrids as potential EGFR-TK inhibitors and apoptosis-inducing agents.

Development of new effective EGFR-targeted antitumor agents is needed because of their clinical significance. A new series of imidazolone-sulphonamide-pyrimidine hybrids was designed and synthesized as modified analogs of some reported EGFR inhibitors. The cytotoxic activity of all the synthesized hybrids was investigated against the breast MCF-7 cancerous cell line using doxorubicin (Dox) as a positive control. 4-(Furan-2-ylmethylene)imidazolone-sulphonamide-pyrimidine 6b had the best potent activity against MCF-7 cells with IC50 result of 1.05 µM, which was better than Dox (IC50 = 1.91 µM). In addition, mechanistic studies revealed the ability of compounds 5g, 5h and 6b to inhibit EGFR kinase. Cell cycle analysis revealed that compound 6b can halt MCF-7 cells at the G1 phase with a concomitant decrease in cellular percentage at the S and G2/M phases. This compound produced a noticeable rise in the proportion of apoptotic cells with regard to the untreated control. Furthermore, the effects of hybrid 6b on the expression levels of pro-apoptotic Bax and pro-survival Bcl2 were assessed. The results showed that this compound upregulated the level of Bax expression as well as declined the expression value of Bcl-2 with regard to the untreated control.

ACTL6A: unraveling its prognostic impact and paving the way for targeted therapeutics in carcinogenesis.

Introduction: Increased Actin-like 6A (ACTL6A) expression is associated with various cancers, but its comprehensive investigation across different malignancies is lacking. We aimed to analyze ACTL6A as a potential oncogene and therapeutic target using bioinformatics tools. Methods: We comprehensively analyzed ACTL6A expression profiles across human malignancies, focusing on correlations with tumor grade, stage, metastasis, and patient survival. Genetic alterations were examined, and the epigenetic landscape of ACTL6A was assessed using rigorous methods. The impact of ACTL6A on immune cell infiltration in the tumor microenvironment was evaluated, along with molecular docking studies and machine learning models. Results: Our analysis revealed elevated ACTL6A expression in various tumors, correlating with poor prognostic indicators such as tumor grade, stage, metastasis, and patient survival. Genetic mutations and epigenetic modifications were identified, along with associations with immune cell infiltration and key cellular pathways. Machine learning models demonstrated ACTL6A's potential for cancer detection. Discussion: ACTL6A emerges as a promising diagnostic and therapeutic target in cancer, with implications for prognosis and therapy. Our study provides comprehensive insights into its carcinogenic actions, highlighting its potential as both a prognostic indicator and a target for anti-cancer therapy. This integrative approach enhances our understanding of ACTL6A's role in cancer pathogenesis and treatment.

Correlation Between C-Reactive Protein and Lipid Analytes in Dry Age-Related Macular Degeneration: A Retrospective Study.

INTRODUCTION: To date few studies have investigated the correlation between inflammatory markers and lipoproteins in the serum of age-related macular degeneration (AMD) patients, often reporting conflicting findings. This study aimed to investigate the correlation between lipid analytes and C-reactive protein (CRP) levels in individuals diagnosed with dry AMD. METHODS: A standard clinical lipid panel (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoproteins) and CRP laboratory results were retrospectively collected from the medical records of patients with dry AMD and age- and sex-matched controls. RESULTS: The study included 90 patients with dry AMD and 270 patients without AMD. In univariate analysis, CRP showed a higher mean value in cases than in controls. After adjusting for age and sex, CRP and triglyceride levels showed significant differences between cases and controls. Pearson's correlation analysis revealed a significant negative correlation between CRP and HDL levels in the dry AMD group (n=90). Other lipid analytes showed no significant correlations with CRP. CONCLUSION: Our findings add to the growing body of evidence linking inflammation to AMD. Although it is unclear whether changes in serum CRP and triglyceride levels are the causes or effects, monitoring both analytes may be beneficial as an early disease predictor, especially in individuals with a family history of AMD. The negative correlation between CRP and HDL (i.e., inflammation and good cholesterol) may be targeted for future therapies.

A pan-cancer analysis reveals CHD1L as a prognostic and immunological biomarker in several human cancers.

Introduction: Several recent studies pointed out that chromodomain-helicase-DNA-binding protein 1-like (CHD1L) is a putative oncogene in many human tumors. However, up to date, there is no pan-cancer analysis performed to study the different aspects of this gene expression and behavior in tumor tissues. Methods: Here, we applied several bioinformatics tools to make a comprehensive analysis for CHD1L. Firstly we assessed the expression of CHD1L in several types of human tumors and tried to correlate that with the stage and grade of the analyzed tumors. Following that, we performed a survival analysis to study the correlation between CHD1L upregulation in tumors and the clinical outcome. Additionally, we investigated the mutation forms, the correlation with several immune cell infiltration, and the potential molecular mechanisms of CHD1L in the tumor tissue. Result and discussion: The results demonstrated that CHD1L is a highly expressed gene across several types of tumors and that was correlated with a poor prognosis for most cancer patients. Moreover, it was found that CHD1L affects the tumor immune microenvironment by influencing the infiltration level of several immune cells. Collectively, the current study provides a comprehensive overview of the oncogenic roles of CHD1L where our results nominate CHD1L as a potential prognostic biomarker and target for antitumor therapy development.

HBD-2 variants and SARS-CoV-2: New insights into inter-individual susceptibility.

Background: A deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (hBD-2) and cathelicidin LL-37] in the defense against SARS-CoV-2, it became important to identify the damaging missense mutations in the genes of these molecules and study their role in the pathogenesis of COVID-19. Methods: We conducted a comprehensive analysis with multiple in silico approaches to identify the damaging missense SNPs for hBD-2 and LL-37; moreover, we applied docking methods and molecular dynamics analysis to study the impact of the filtered mutations. Results: The comprehensive analysis reveals the presence of three damaging SNPs in hBD-2; these SNPs were predicted to decrease the stability of hBD-2 with a damaging impact on hBD-2 structure as well. G51D and C53G mutations were located in highly conserved positions and were associated with differences in the secondary structures of hBD-2. Docking-coupled molecular dynamics simulation analysis revealed compromised binding affinity for hBD-2 SNPs towards the SARS-CoV-2 spike domain. Different protein-protein binding profiles for hBD-2 SNPs, in relation to their native form, were guided through residue-wise levels and differential adopted conformation/orientation. Conclusions: The presented model paves the way for identifying patients prone to COVID-19 in a way that would guide the personalization of both the diagnostic and management protocols for this serious disease.

Evaluation of Expressed MicroRNAs as Prospective Biomarkers for Detection of Breast Cancer.

Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non-invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR-34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2−negative (p < 0.001), estrogen receptor−positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.

Integrative analysis of WDR12 as a potential prognostic and immunological biomarker in multiple human tumors.

Background: Mammalian WD-repeat protein 12 (WDR12), a family member of proteins containing repeats of tryptophan-aspartic acid (WD), is a potential homolog of yeast Ytm1p and consists of seven repeats of WD. Aim of the study: This study aims to investigate the potential oncogenic effects of WDR12 in various human malignancies throughout a pan-cancer analysis that has been carried out to examine the various patterns in which this gene is expressed and behaves in tumor tissues. Methods: Herein, we used The Cancer Genome Atlas (TCGA) and various computational tools to explore expression profiles, prognostic relevance, genetic mutations, immune cell infiltration, as well as the functional characteristics of WDR12 in multiple human cancers. Results: We found that WDR12 was inconsistently expressed in various cancers and that variations in WDR12 expression predicted survival consequences for cancer patients. Furthermore, we observed a significant correlation between WDR12 gene mutation levels and the prognosis of some tumors. Furthermore, significant correlations were found between WDR12 expression patterns and cancer-associated fibroblast (CAF) infiltration, myeloid-derived suppressor cells (MDSCs), tumor mutation burden, microsatellite instability and immunoregulators. Ultimately, pathway enrichment analysis revealed that WDR12-related pathways are involved in carcinogenesis. Conclusions: The findings of our study are stisfactory, demonstrating that WDR12 could serve as a promising reliable prognostic biomarker, as well as a therapeutic target for novel cancer therapeutic approaches.