Ari Qadir Nabi

Background: Mitochondrial dysfunction is a key contributor to the pathophysiology of cardiovascular disease (CVD), one of the leading causes of morbidity and mortality worldwide. Mitochondria-associated microRNAs (mitomiRs) have emerged as critical regulators of mitochondrial homeostasis and cardiac function; however, their clinical utility as circulating biomarkers remains incompletely defined. This study aimed to evaluate the diagnostic potential of circulating hsa-miR-181c-5p and hsa-miR-106a-5p in patients with CVD and to assess their applicability as early, non-invasive biomarkers in an Iraqi cohort. Methods: In this case–control study, plasma samples were obtained from 30 patients with clinically diagnosed cardiovascular disease and 30 age-matched healthy controls. Total RNA was extracted, followed by complementary DNA synthesis. Expression levels of hsa-miR-181c-5p and hsa-miR-106a-5p were quantified using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Plasma levels of hsa-miR-181c-5p were significantly upregulated in CVD patients, exhibiting a three-fold increase compared with controls ( p = 0.0001). Likewise, hsa-miR-106a-5p expression was elevated by approximately four-fold in the CVD group ( p = 0.0008). ROC analysis demonstrated robust discriminatory power for both miRNAs, with an area under the curve (AUC) of 0.796 for hsa-miR-181c-5p ( p = 0.0002) and 0.749 for hsa-miR-106a-5p ( p = 0.0010). Conclusions: Our findings identify circulating hsa-miR-181c-5p and hsa-miR-106a-5p as promising mitomiR-based biomarkers for cardiovascular disease. Their significant upregulation and diagnostic accuracy support their potential role in early, non-invasive detection of CVD and highlight the clinical relevance of mitochondrial miRNA dysregulation in cardiovascular pathology.

The current view of the mitochondrial respiratory chain complexes I, III and IV foresees the occurrence of their assembly in supercomplexes, providing additional functional properties when compared with randomly colliding isolated complexes. According to the plasticity model, the two structural states of the respiratory chain may interconvert, influenced by the intracellular prevailing conditions. In previous studies, we suggested the mitochondrial membrane potential as a factor for controlling their dynamic balance. Here, we investigated if and how the cAMP/PKA-mediated signalling influences the aggregation state of the respiratory complexes. An analysis of the inhibitory titration profiles of the endogenous oxygen consumption rates in intact HepG2 cells with specific inhibitors of the respiratory complexes was performed to quantify, in the framework of the metabolic flux theory, the corresponding control coefficients. The attained results, pharmacologically inhibiting either PKA or sAC, indicated that the reversible phosphorylation of the respiratory chain complexes/supercomplexes influenced their assembly state in response to the membrane potential. This conclusion was supported by the scrutiny of the available structure of the CI/CIII₂/CIV respirasome, enabling us to map several PKA-targeted serine residues exposed to the matrix side of the complexes I, III and IV at the contact interfaces of the three complexes.

The current view of the mitochondrial respiratory chain complexes I, III and IV foresees the oc-currence of their assembly in supercomplexes providing additional functional properties as compared with randomly colliding isolated complexes. According to the plasticity model, these two structural states of the respiratory chain may interconvert influenced by the intracellular prevailing conditions and in previous studies we candidated the mitochondrial membrane po-tential as a factor controlling their dynamic balance. Here, we extended those studies investigating if and how the cAMP/PKA-mediated signalling influences the aggregation state of the respiratory complexes. Analysis of inhibitory-titration profiles of the endogenous oxygen consumption rates in intact HepG2 cells with specific inhibitors of the respiratory complexes was performed to quantify, in the framework of the metabolic flux theory, the corresponding control coefficients. The results attained inhibiting pharmacologically either PKA and sAC indicate that the reversible phosphorylation of the respiratory chain complexes/supercomplexes influences their assembly state in response to the membrane potential. This conclusion is supported by scrutiny of the available structure of the CI,CIII2,CIV respirasome enabling to map several PKA-target serine residues exposed to the matrix side of the complexes I, III and IV at the contact interfaces of the three complexes.

Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as “signature microRNA OR miR” AND “HNSCC OR LSCC OR OSCC OR oral cancer” were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.

Alzheimers disease (AD) is a neurological, age-related condition that causes cognitive decline and memory loss; it induces dementia in the elderly. Telomerase is a reverse transcriptase ribonucleoprotein that adds nucleotides to the end of DNA. This study aimed to compare human telomerase reverse transcriptase (hTERT) and telomerase RNA component (TERC) expression in different phases of AD and healthy cohorts. Sixty participants were divided into 30 who had dementia and 30 who did not. After collecting blood samples, total RNAs were extracted from the plasma. Screening for hTERT and TERC gene expression was carried out by quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR) using the relative quantification method to estimate the expression changes in hTERT and TERC. The RT-qPCR results show that hTERT and TERC gene expression was significantly down-regulated in Alzheimers patients compared to the health subjects (P-value=

Studying the genes related with antimicrobial resistance in Salmonella spp. is a crucial step toward a correct and faster treatment of infections caused by the pathogen. In this work Integron mediated antibiotic resistant gene IntI1 (Class I Integrase IntI1) and some plasmid mediated antibiotic resistance genes (Qnr) were scanned among the isolated non-Typhoid Salmonellae strains with known resistance to some important antimicrobial drugs using Sybr Green real time PCR. The aim of the study was to correlate the multiple antibiotics and antimicrobial resistance of Salmonella spp. with the presence of integrase (IntI1) gene and plasmid mediated quinolone resistant genes. Results revealed the presence of Class I Integrase gene in 76% of the isolates with confirmed multiple antibiotic resistances. Moreover, about 32% of the multiple antibiotic resistant serotypes showed a positive R-PCR for plasmid mediated qnrA gene encoding for nalidixic acid and ciprofloxacin resistance. No positive results could be revealed form R-PCRs targeting qnrB or qnrS. In light of these results we can conclude that the presence of at least one of the qnr genes and/or the presence of Integrase Class I gene were responsible for the multiple antibiotic resistance to for nalidixic acid and ciprofloxacin from the studied Salmonella spp. and further studies required to identify the genes related with multiple antibiotic resistance of the pathogen.

A total of 48 samples of ready to-eat salads (RTE), containing different varieties of salads, of different brands sold in Italy, were purchased from several supermarkets, during period 2008 – 2009. This study was performed to determine whether microbial contamination, and in particular pathogenic bacteria, such as Listeria monocytogenes, were present in these food products. Samples were examined for mesophilic aerobic counts, yeasts and moulds, total and fecal coliforms, and presumptive Listeria monocytogenes counts. Results showed that, in general, the highest microorganism counts were associated with samples containing grated carrot (6.3 Log cfu g-1 of aerobic mesophilic microorganisms; 4.6 Log cfu g-1 of yeast and moulds; 2.8 Log cfu g-1 of total coliforms), while the lowest counts were, generally, associated with samples containing lettuce (2.8 Log cfu g-1 of aerobic mesophilic microorganisms; 2.3 Log cfu g-1 of yeast and moulds; 2.3 Log cfu g-1 of total coliforms). Of all the samples analyzed, only three (6 %) harboured L. monocytogenes.