PCSK9 pathway-noncoding RNAs crosstalk: Emerging opportunities for novel therapeutic approaches in inflammatory atherosclerosis.

A variety of mechanisms contribute to the occurrence and development of inflammatory atherosclerosis (IA), resulting in cardiovascular disease. PCSK9 (proprotein convertase subtilisin/ kexin type 9) has now been recognized as a key player in the pathophysiology of atherosclerosis. Following PCSK9 activation, LDL receptors (LDLR) are degraded and as a result, LDL cholesterol (LDLC) levels are increased. Increasing evidence reports that the PCSK9 axis mediates IA through different pathways, such as LDLR, LOX1, NF-kB, and TLR4. In recent years, PCSK9 pathway dysregulation has been identified as one of the fundamental mechanisms involved in IA. Recently, the importance of epigenetic factors, in particular, in non-coding RNAs, including miRNAs and long ncRNAs (lncRNAs) as well as circular RNAs (circRNAs) in the regulation of physiological and pathological events has received great attention. In this regard, an expanding body of research has revealed that different ncRNAs play important roles in the progression of inflammatory atherosclerosis through targeting genes related to the PCSK9 pathway at the post-transcriptional level. Of importance, the current study aimed to review the relationship between the various ncRNAs and PCSK9 pathway to identify the molecular mechanisms underlying IA pathogenesis as well as to introduce the novel PCSK9 pathway-related therapeutic interventions in combating IA.

The emerging role of microbiota-derived short-chain fatty acids in immunometabolism.

The accumulating evidence revealed that microbiota plays a significant function in training, function, and the induction of host immunity. Once this interaction (immune system-microbiota) works correctly, it enables the production of protective responses against pathogens and keeps the regulatory pathways essential for maintaining tolerance to innocent antigens. This concept of immunity and metabolic activity redefines the realm of immunometabolism, paving the way for innovative therapeutic interventions to modulate immune cells through immune metabolic alterations. A body of evidence suggests that microbiota-derived metabolites, including short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate, play a key role in immune balance. SCFAs act on many cell types to regulate various vital biological processes, including host metabolism, intestinal function, and the immune system. Such SCFAs generated by gut bacteria also impact immunity, cellular function, and immune cell fate. This is a new concept of immune metabolism, and better knowledge about how lifestyle affects intestinal immunometabolism is crucial for preventing and treating disease. In this review article, we explicitly focus on the function of SCFAs in the metabolism of immune cells, especially macrophages, neutrophils, dendritic cells (DCs), B cells, T (Th) helper cells, and cytotoxic T cells (CTLs).

Virulence traits and plasmid-mediated quinolone resistance among Aggregatibacter actinomycetemcomitans from Iraq: Low rate of highly virulent JP2 genotype.

Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is an important causative agent of periodontitis acting by employment of a series of virulence factors. Our aim was to evaluate the virulence traits and plasmid-mediated quinolone resistance of A. actinomycetemcomitans isolates in Iraq. A total of 1580 samples were collected from dental caries (n = 1190) and periodontitis (n = 390) among which 200 samples were positive. The antibiotic susceptibility pattern and biofilm formation were performed. The antibiotic resistance and virulence determinants were screened using polymerase chain reaction (PCR) technique. The ltx3 and ltx4 primers were used for identification of highly virulent JP2 type. A. actinomycetemcomitans was identified among dental caries (n = 114) and periodontitis (n = 86) samples. The JP2 type was identified in six periodontitis samples. Sixty (30% of) isolates were multidrug-resistant (MDR). Eighty-four (42% of) A. actinomycetemcomitans isolates formed strong biofilms and 44% of them had moderate-level biofilms. The detected virulence genes included ltxA (96%), cdtB (64%), qseB (62%), qseC (58%) and rcpA (58%). There was a significant relation between the existence of ltxA (42%, p = 0.041) and rcpA (64%, p = 0.022) genes and the biofilm formation. The JP2 genotype was identified in six adolescents with periodontitis. The rate of qnrA, qnrB, qnrC, qnrD, qnrS and aac(6')-Ib-cr plasmid-mediated quinolone resistance genes included 22%, 18%, 16%, 16%, 14% and 0%, respectively. The qnrA (66.7%) and qnrB (53.4%) genes were significantly detected higher in MDR strains. Herein, A. actinomycetemcomitans from dental caries and periodontitis had relatively high rate of resistance to ß-lactams but low resistance levels to quinolones. Moreover, most of the resistant isolates carried the qnrA-S genes. A majority of them had ltxA gene, half of them contained all the virulence genes and JP2 genotype was found in six isolates from periodontitis. Furthermore, half of the isolates produced biofilms which was significantly related to the ltxA and rcpA genes. Screening of virulence genes and antibiotic resistance pattern determination contribute to the control, diagnosis and eradication of these isolates.

Biocontrol of Rhizoctonia solani (Kühn) and Fusarium solani (Marti) causing damping-off disease in tomato with Azotobacter chroococcum and Pseudomonas fluorescens.

BACKGROUND AND OBJECTIVE: The Damping-off disease is one of the most reasons for low productively of tomato in the world, especially in Iraq. In the current study, two types of bacteria (Azotobacter chroococcum and Pseudomonas fluorescens) were used to evaluate their efficacy in inhibiting the growth of pathogenic fungi Rhizoctonia solani and Fusarium solani and protecting the seeds of tomato and increasing their germination percentage. MATERIALS AND METHODS: Dual culture technique and Food poisoning technique were used to study the effect of bacteria on the growth of fungi understudy, and study the effect of bacterial filtrates on germination of tomato seeds. RESULTS: A. chroococcum showed the strongest antagonistic activity followed by P. fluorescens with the percentage of inhibition ranging between 72.9-77.1 and 69.5-70.3% for R. solani and F. solani respectively after 7 days of incubation. The effect of A. chroococcum and P. fluorescens filtrates were increased and also increased the inhibition of growth of fungi understudy, A. chroococcum filtrate also showed the strongest inhibitory effect followed by P. fluorescens with the percentage of inhibition ranging between 86.0-87.0 and 83.0-83.5% for R. solani and F. solani respectively at 20% concentration of filtrate. The percentage of seeds germination reached 90% in the treatment of A. chroococcum filtrate and 80% in the treatment of P. fluorescens filtrate. CONCLUSION: It can be concluded that the filtrates of A. chroococcum and P. fluorescens have antifungal properties against R. solani and F. solani and provided a high protection and increasing tomato seeds germination percentage.