Exosomal microRNA as a key regulator of PI3K/AKT pathways in human tumors.

MicroRNAs (miRNAs) are conserved non-protein-coding RNAs that are naturally present in organisms and can control gene expression by suppressing the translation of mRNA or causing the degradation of mRNA. MicroRNAs are highly concentrated in the PI3K/AKT pathway, and abnormal activation of the PI3K/AKT pathway plays a role in cancer progression. The AKT/PI3K pathway is critical for cellular functions and can be stimulated by cytokines and in normal situations. It is involved in regulating various intracellular signal transduction, including development, differentiation, transcriptional regulation, protein, and synthesis. There is a growing body of evidence indicating that miRNAs, which are abundant in exosomes released by different cells, can control cellular biological activities via modulating the PI3K/AKT pathway, hence influencing cancer progression and drug resistance. This article provides an overview of the latest research progress regarding the function and medical use of the PI3K/AKT pathway and exosomal miRNA/AKT/PI3K axis in the behaviors of cancer cells.

Investigation of dual inhibition of antibacterial and antiarthritic drug candidates using combined approach including molecular dynamics, docking and quantum chemical methods.

Emerging antibiotic resistance in bacteria threatens immune efficacy and increases susceptibility to bone degradation and arthritic disorders. In our current study, we utilized a three-layer in-silico screening approach, employing quantum chemical methods, molecular docking, and molecular dynamic methods to explore the novel drug candidates similar in structure to floroquinolone (ciprofloxacin). We investigated the interaction of novel similar compounds of ciprofloxacin with both a bacterial protein S. aureus TyrRS (1JIJ) and a protein associated with gout arthritis Neutrophil collagenase (3DPE). UTIs and gout are interconnected through the elevation of uric acid levels. We aimed to identify compounds with dual functionality: antibacterial activity against UTIs and antirheumatic properties. Our screening based on several methods, sorted out six promising ligands. Four of these (L1, L2, L3, and L6) demonstrated favorable hydrogen bonding with both proteins and were selected for further analysis. These ligands showed binding affinities of -8.3 to -9.1 kcal/mol with both proteins, indicating strong interaction potential. Notably, L6 exhibited highest binding energies of -9.10 and -9.01 kcal/mol with S. aureus TyrRS and Neutrophil collagenase respectively. Additionally, the pkCSM online database conducted ADMET analysis on all lead ligand suggested that L6 might exhibit the highest intestinal absorption and justified total clearance rate. Moreover, L6 showed a best predicted inhibition constant with both proteins. The average RMSF values for all complex systems, namely L1, L2, L3 and L6 are 0.43 Å, 0.57 Å, 0.55 Å, and 0.51 Å, respectively where the ligand residues show maximum stability. The smaller energy gap of 3.85 eV between the HOMO and LUMO of the optimized molecule L1 and L6 suggests that these are biologically active compound. All the selected four drugs show considerable stabilization energy ranging from 44.78 to 103.87 kcal/mol, which means all four compounds are chemically and physically stable. Overall, this research opens exciting avenues for the development of new therapeutic agents with dual functionalities for antibacterial and antiarthritic drug designing.

Colistin, doxycycline and Labetalol-meropenem combination are the most active against XDR-Carbapenem-resistant Acinetobacter baumannii: Role of a novel transferrable plasmid conferring carbapenem resistance.

This study aimed to evaluate the antimicrobial susceptibility and combination of a beta-blocker, labetalol (LAB) and meropenem (MEM) on Carbapenem-resistant (CR) A. baumannii clinical isolates. A total of 43 CR- A. baumannii were isolated of which 37 (86.6 %) and 28 (65 %) exhibited MDR and XDR phenotypes, respectively. Colistin and doxycycline still retain their activities in 93.1 % and 72.1 % of the isolates, respectively. Combining MEM with LAB at 0.25 mg /mL, decreased MIC values in 91.4 % (32/35) however, at 0.5 mg /mL, it decreased MIC value and restored susceptibility to MEM in 100 % and 91.4 % of the tested isolates, respectively. A novel transferable plasmid pAcbGIM3 harboring aph-3', blaoxa-58,blaGIM3 and blaCTX-M3 and eight mobile genetic elements were successfully isolated from a pan-drug resistant (PDR) isolate. In conclusion, LAB-MEM is a promising combination and should be clinically examined. This is the first report of a transmissible plasmid harboring blaGIM3 gene in Egypt.

Impact of Rumex nepalensis on Performance, Blood Markers, Immunity, Intestinal Microbiology and Histomorphology in Broiler Chicken.

The study investigated the impact of utilizing Rumex nepalensis leaf powder (RNL) as a phytogenic feed additive on performance, blood markers, intestinal microbiology and histomorphology in broiler chicken. One hundred eighty day-old Cobb broiler chicks were randomly divided into four treatment groups having three replicates with fifteen birds each. Four iso-caloric and iso-nitrogenous diets primarily based on maize-soybean were formulated, viz., CN (Control)-fed basal diet only; RNL2.5 (basal diet + 2.5 g/kg RNL); RNL5 (basal diet + 5 g/kg RNL); and RNL10 (basal diet + 10 g/kg RNL). The results revealed a significant (p < 0.05) increase in body weight gain and feed conversion ratio in dietary treatments compared to CN with best values in RNL10 followed by RNL5. The blood markers like glucose, total protein, creatinine, alanine transaminase (ALT) and aspartate transaminase (AST) showed no significance (p > 0.05) among all the treatments, however total cholesterol significantly (p < 0.05) decreased in RNL5 and RNL10 as against CN. Regarding immune parameters, immunoglobulin G (IgG) and immunoglobulin M (IgM) levels significantly (p < 0.05) enhanced in RNL5 and RNL10. Antioxidant enzyme status showed that superoxide dismutase (SOD) increased and malondialdehyde (MDA) decreased significantly (p < 0.05) in RNL10 compared to CN. Gut health in terms of cecal microbiology and histomorphology of duodenum and jejunum were altered by inclusion of RNL in the broiler diet. A significant decrease (p < 0.05) in coliform count was recorded by incorporation of dietary treatments with highest reduction in RNL10. Lactobacillus count and total viable count did not vary significantly (p > 0.05) among dietary treatments and CN. Duodenal and jejunal villus height and villus height/crypt depth ratio were significantly (p < 0.05) increased in RNL5 and RNL10 compared to RNL2.5 and CN. Thus, it could be concluded that inclusion of Rumex nepalensis leaf powder in the diet resulted in improved performance and better immuno-antioxidant status of broilers. Further, an improvement in the gut health was observed in terms of positive effects on cecal microbiota and intestinal histomorphology of broiler chickens.

siRNA-based strategies to combat drug resistance in gastric cancer.

Chemotherapy is a key treatment option for gastric cancer, but over 50% of patients develop either inherent or acquired resistance to these drugs, resulting in a 5-year survival rate of only about 20%. The primary treatment for advanced gastric cancer typically involves chemotherapy based on platinum or fluorouracil. Several factors can contribute to platinum resistance, including decreased drug uptake, increased drug efflux or metabolism, enhanced DNA repair, activation of pro-survival pathways, and inhibition of pro-apoptotic pathways. In recent years, there has been significant progress in biology aimed at finding innovative and more effective methods to overcome chemotherapy resistance. Small interfering RNAs (siRNAs) have emerged as a significant advancement in gene expression regulation, showing promise in enhancing the sensitivity of gastric cancer cells to chemotherapy drugs. However, siRNA therapies still face major challenges, particularly in terms of stability and efficient delivery in vivo. This article discusses the advances in siRNA therapy and its potential role in overcoming resistance to chemotherapeutic drugs such as cisplatin, 5-FU, doxorubicin, and paclitaxel in the treatment of gastric cancer.

Combinatorial biosynthesis of novel aminoglycoside antibiotics via pathway engineering.

With the current spread of clinically relevant multidrug-resistant (MDR) pathogens, insufficient unearthing of new anti-infectives, and the high cost required for approval of new antimicrobial agents, a strong need for getting these agents via more economic and other alternative routes has emerged. With the discovery of the biosynthetic pathways of various antibiotics pointing out the role of each gene/protein in their antibiotic-producing strains, it became apparent that the biosynthetic gene clusters can be manipulated to produce modified antibiotics. This new approach is known as the combinatorial biosynthesis of new antibiotics which can be employed for obtaining novel derivatives of these valuable antibiotics using genetically modified antibiotic-producing strains (pathway engineering). In this review and based on the available biosynthetic gene clusters of the major aminoglycoside antibiotics (AGAs), the possible alterations or modifications that could be done by co-expression of certain gene(s) previously known to be involved in unique biosynthetic steps have been discussed. In this review defined novel examples of modified AGA using this approach were described and the information provided will act as a platform of researchers to get and develop new antibiotics by the antibiotic-producing bacterial strains such as Streptomyces, Micromonospora,…etc. This way, novel antibiotics with new biological activities could be isolated and used in the treatment of infectious diseases conferring resistance to existing antibiotics.

Central composite design for optimizing istamycin production by Streptomyces tenjimariensis.

Istamycins (ISMs) are 2-deoxyfortamine-containing aminoglycoside antibiotics (AGAs) produced by Streptomyces tenjimariensis ATCC 31603 with broad-spectrum bactericidal activities against most of the clinically relevant pathogens. Therefore, this study aimed to statistically optimize the environmental conditions affecting ISMs production using the central composite design (CCD). Both the effect of culture media composition and incubation time and agitation rate were studied as one factor at the time (OFAT). The results showed that both the aminoglycoside production medium and the protoplast regeneration medium gave the highest specific productivity. Results also showed that 6 days incubation time and 200 rpm agitation were optimum for their production. A CCD quadratic model of 17 runs was employed to test three key variables: initial pH, incubation temperature, and concentration of calcium carbonate. A significant statistical model was obtained including, an initial pH of 6.38, incubation temperature of 30 ˚C, and 5.3% CaCO3 concentration. This model was verified experimentally in the lab and resulted in a 31-fold increase as compared to the unoptimized conditions and a threefold increase to that generated by using the optimized culture media. To our knowledge, this is the first report about studying environmental conditions affecting ISM production as OFAT and through CCD design of the response surface methodology (RSM) employed for statistical optimization. In conclusion, the CCD design is an effective tool for optimizing ISMs at the shake flask level. However, the optimized conditions generated using the CCD model in this study should be scaled up in a fermenter for industrial production of ISMs by S. tenjimariensis ATCC 31603 considering the studied environmental conditions that significantly influence the production proces.

AI-enabled sports-system peer-to-peer energy exchange network for remote areas in the digital economy.

In remote areas, particularly in developing countries, there is a growing interest in off-grid solar PV systems for their ability to provide clean and affordable electricity. However, these systems often face limitations in powering essential amenities, including sports facilities, due to restricted capabilities and inadequate battery storage. To address these challenges and promote energy independence, this paper proposes an AI-enabled sports-system peer-to-peer (P2P) energy exchange network within the digital economy. This innovative system leverages AI to optimize energy distribution specifically for sports-related infrastructures, ensuring efficient use of solar power and improved energy availability for both recreational and community needs. The proposed P2P network operates on a three-part Internet of Things (IoT) framework, facilitating automatic energy sharing among interconnected systems. This approach not only enhances the performance of existing solar power setups but also ensures that energy demands for sports facilities are met effectively. Feasibility studies of this system reveal promising outcomes, including a 13.67% increase in community energy independence and a 12.20% reduction in overall energy consumption. The AI-powered sports-system network demonstrates its potential to support sustainable development and improve the quality of life in remote areas by integrating sports and energy needs within the digital economy context.

Determinants Affecting the Awareness of Hypertension Complications within the General Population in Saudi Arabia.

BACKGROUND: Hypertension imposes a significant public health burden. An increased awareness of hypertension complications within a population can positively impact patient care and prevent complications. This study seeks to assess the awareness of hypertension complications among the population of Bisha in Saudi Arabia in 2020. METHODS: A cross-sectional study was conducted in 2020. A validated self-administered online-based questionnaire was sent to a sample of the adult population of Bisha to measure their awareness of hypertension complications. RESULTS: Almost three-quarters of the population (72.2%) were aware of hypertension complications. The awareness level was significantly higher among male participants (p < 0.001), those aged 31-40 years, those who were married, those working as police officers or in civilian jobs, those living in urban areas (p = 0.04), those with a university-level education (p = 0.03), those with a medium family income (SAR 5000-14,999) (p = 0.001), and those with a history of hospitalization because of causes other than hypertension (p = 0.05). Marital status was independently predictive of awareness (B = 0.851, Wald test = 12.179, p = 0.000) among the respondents. CONCLUSION: The study concludes that the awareness of hypertension complications among the Bisha population in Saudi Arabia was deemed acceptable. Factors such as marital status, age, gender, a family history of hypertension, the duration of hypertension, and medication adherence positively influenced this awareness and served as predictors of hypertensive awareness. The findings highlight the importance of health authorities in ensuring the widespread awareness of hypertension complications, particularly among hypertensive individuals.

Hematological, inflammatory and serological responses among COVID-19 patients admitted to intensive care unit.

Aim: To correlate hematological, inflammatory indicators and serological responses among COVID-19 patients to point out the significant biomarkers for disease management and prognosis.Materials & methods: Standard analytical and molecular methods were used to assess various inflammatory and serological Responses among COVID-19 patients (ICU- (n = 99) and non-ICU patients (n = 64) as compared with health control (n = 40).Results: Significant differences in the Hb, WBC, Lymphocyte count, CRP and serum ferritin (p < 0.05) were observed. Patients' IgM/IgG antibodies against SARS-CoV-2 were associated with increased CRP, LDH and serum ferritin levels.Conclusion: A significant association between serum IgG/IgM and ICU admission was observed. Although serum ferritin and LDH can offer information about the extent of inflammation, they are exclusive factors for ICU admission.

This study aimed to find the best biomarkers among COVID-19 patients to be used as indicators of patient eligibility for admission to the intensive care unit and for evaluating the disease complications and proper intervention before cases deteriorated. For the COVID-19 as compared with healthy individuals, results showed significant differences in many hematological indicators such as hemoglobin level, white blood cells and Lymphocyte count. Results also showed a strong correlation between certain serum antibody levels against COVID-19 and admission to intensive care unit.

The influence of dietary supplementation with fermented agro-industrial residue of faba bean on Japanese quail performance, immunity, gut microbiota, blood chemistry, and antioxidant status.

Antibiotic overuse in poultry feeds has disastrous implications; consequently, long-term alternatives must be developed. As a result, the current study aims to assess the impact of Aspergillus niger filtrate (ANF) high in organic acids grown on agro-industrial residue of faba bean (AIRFB) on quail diet, as well as their influence on bird productivity, digestion, carcass yield, blood chemistry, and intestinal microbiota. A total of 240 Japanese quails (aged 7 d) were used in this study, divided equally among 5 experimental groups with 48 quails each. Group 1 (G1) received a basal diet without any ANF, group 2 (G2) received a basal diet supplemented with 0.5 mL ANF/kg diet, group 3 (G3) received a basal diet supplemented with 1.0 mL ANF/kg diet, group 4 (G4) received a basal diet supplemented with 1.5 mL ANF/kg diet, and group 5 (G5) received a basal diet supplemented with 2 mL ANF/kg diet. The performance parameters were monitored at 1 to 3, 3 to 5, and 1 to 5 wk. Adding ANF increased body weight at 3 and 5 wk, as well as body weight gain at 1 to 3, 3 to 5, and 1 to 5 wk, compared to the control diet. The ANF fed quails had the highest feed conversion ratio compared to the control group. The addition of ANF to the quail diet had no effect on the weight of the carcass, gizzard, heart, liver, giblets, or dressing; however, it did lower triglycerides, low-density lipoprotein, and very low-density lipoprotein while increasing high-density lipoprotein levels. The quail groups that received ANF had enhanced immunological indices such as IgG, IgM, IgA, and lysozymes. It also increased the levels of superoxide dismutase and total antioxidant contents, as well as catalase, and digestive enzymes such as protease, amylase, and lipase. However, it lowered the blood MDA levels compared to control. It has been demonstrated that the total gut microbiota, Escherichia coli, total coliforms, and the population of Salmonella are all reduced in ANF-fed quails. Histological examination of ANF quails' liver and intestinal sections revealed normal hepatic parenchyma, typical leaf-like intestinal villi, and comparatively short and frequently free lumina. In conclusion, Japanese quail showed improvements in performance, digestive enzymes, antioxidant indices, immunity, and capacity to reduce intestinal pathogenic bacteria after consuming diet supplemented with ANF.

Machine learning investigation of tuberculosis with medicine immunity impact.

Tuberculosis (T.B.) remains a prominent global cause of health challenges and death, exacerbated by drug-resistant strains such as multidrug-resistant tuberculosis MDR-TB and extensively drug-resistant tuberculosis XDR-TB. For an effective disease management strategy, it is crucial to understand the dynamics of T.B. infection and the impacts of treatment. In the present article, we employ AI-based machine learning techniques to investigate the immunity impact of medications. SEIPR epidemiological model is incorporated with MDR-TB for compartments susceptible to disease, exposed to risk, infected ones, preventive or resistant to initial treatment, and recovered or healed population. These masses' natural trends, effects, and interactions are formulated and described in the present study. Computations and stability analysis are conducted upon endemic and disease-free equilibria in the present model for their global scenario. Both numerical and AI-based nonlinear autoregressive exogenous NARX analyses are presented with incorporating immediate treatment and delay in treatment. This study shows that the active patients and MDR-TB, both strains, exist because of the absence of permanent immunity to T.B. Furthermore, patients who have recovered from tuberculosis may become susceptible again by losing their immunity and contributing to transmission again. This article aims to identify patterns and predictors of treatment success. The findings from this research can contribute to developing more effective tuberculosis interventions.

Multi-epitope peptide vaccines targeting dengue virus serotype 2 created via immunoinformatic analysis.

The Middle East has witnessed a greater spread of infectious Dengue viruses, with serotype 2 (DENV-2) being the most prevalent form. Through this work, multi-epitope peptide vaccines against DENV-2 that target E and nonstructural (NS1) proteins were generated through an immunoinformatic approach. MHC class I and II and LBL epitopes among NS1 and envelope E proteins sequences were predicted and their antigenicity, toxicity, and allergenicity were investigated. Studies of the population coverage denoted the high prevalence of NS1 and envelope-E epitopes among different countries where DENV-2 endemic. Further, both the CTL and HTL epitopes retrieved from NS1 epitopes exhibited high conservancies' percentages with other DENV serotypes (1, 3, and 4). Three vaccine constructs were created and the expected immune responses for the constructs were estimated using C-IMMSIM and HADDOCK (against TLR 2,3,4,5, and 7). Molecular dynamics simulation for vaccine construct 2 with TLR4 denoted high binding affinity and stability of the construct with the receptor which might foretell favorable in vivo interaction and immune responses.

Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches.

Pulmonary toxicity is a serious side effect of some specific anticancer drugs. Bleomycin is a well-known anticancer drug that triggers severe reactions in the lungs. It is an approved drug that may be prescribed for the treatment of testicular cancers, Hodgkin's and non-Hodgkin's lymphomas, ovarian cancer, head and neck cancers, and cervical cancer. A large number of experimental studies and clinical findings show that bleomycin can concentrate in lung tissue, leading to massive oxidative stress, alveolar epithelial cell death, the proliferation of fibroblasts, and finally the infiltration of immune cells. Chronic release of pro-inflammatory and pro-fibrotic molecules by immune cells and fibroblasts leads to pneumonitis and fibrosis. Both fibrosis and pneumonitis are serious concerns for patients who receive bleomycin and may lead to death. Therefore, the management of lung toxicity following cancer therapy with bleomycin is a critical issue. This review explains the cellular and molecular mechanisms of pulmonary injury following treatment with bleomycin. Furthermore, we review therapeutic targets and possible promising strategies for ameliorating bleomycin-induced lung injury.

Effectiveness of Pre-Transplant Screening for High-Priority Multidrug-Resistant Pathogens on Pre-Engraftment Infections After Hematopoietic Stem Cell Transplantation.

Objective: Owing to the rising incidence of multidrug-resistant organisms (MDRO) and the high mortality rates associated with such bacterial infections post-hematopoietic stem cell transplantation (HSCT), we investigated the MDRO colonization rate prior to transplantation using an active surveillance approach and determined its impact on subsequent infection during the pre-engraftment period. Methods: A single-center observational study was conducted, and surveillance cultures from multiple body sites, including the rectum, nasal cavity, and groin, were performed at admission to determine MDRO colonization. Serological tests were used to detect certain viruses and toxoplasmosis before HSCT. Results: In the pre-transplant setting, 59 MDRO were recovered from the 40 HSCT recipients. Of the 59 isolates recovered from one or more body sites, 29 were positive for methicillin-resistant Staphylococcus aureus (MRSA), 7 for carbapenem-resistant Enterobacterales (CRE), and 23 were positive for extended-spectrum ß-lactamase (ESBLs). Serological assessment before HSCT revealed active or reactivation of latent infection with cytomegalovirus (7.5%), Epstein-Barr virus (EBV; 5%), and Toxoplasma gondii (2.5%) among HSCT patients. In terms of factors associated with pre-engraftment infections, the type of transplant (p=0.04) was statistically significant, whereas other factors, such as age, sex, and underlying conditions, were not. In post-transplant settings, bloodstream infections (BSIs) were documented in 2 allogeneic HSCT patients (5%), and the isolated microorganisms were ESBL-producing E. coli and non-MDR Acinetobacter baumannii. Conclusion: Active screening cultures are a helpful tool for identifying patients colonized by MDRO or relevant viruses before HSCT, and for predicting those at risk of developing subsequent pre-engraftment infections. Additionally, active screening may aid in predicting those who are likely to develop subsequent pre-engraftment infections Our findings highlight the importance of pre-transplant screening for high-priority multidrug-resistant pathogens and the application of infection control interventions after HSCT.

A comprehensive insight into the immunomodulatory role of MSCs-derived exosomes (MSC-Exos) through modulating pattern-recognition receptors (PRRs).

Mesenchymal stem cell-derived exosomes (MSC-Exos) are emerging as remarkable agents in the field of immunomodulation with vast potential for diagnosing and treating various diseases, including cancer and autoimmune disorders. These tiny vesicles are laden with a diverse cargo encompassing proteins, nucleic acids, lipids, and bioactive molecules, offering a wealth of biomarkers and therapeutic options. MSC-Exos exhibit their immunomodulatory prowess by skillfully regulating pattern-recognition receptors (PRRs). They conduct a symphony of immunological responses, modulating B-cell activities, polarizing macrophages toward anti-inflammatory phenotypes, and fine-tuning T-cell activity. These interactions have profound implications for precision medicine, cancer immunotherapy, autoimmune disease management, biomarker discovery, and regulatory approvals. MSC-Exos promises to usher in a new era of tailored therapies, personalized diagnostics, and more effective treatments for various medical conditions. As research advances, their transformative potential in healthcare becomes increasingly evident.

Evaluation of fortimicin antibiotic combinations against MDR Pseudomonas aeruginosa and resistome analysis of a whole genome sequenced pan-drug resistant isolate.

BACKGROUND: Multidrug-resistant (MDR) P. aeruginosa is a rising public health concern, challenging the treatment of such a ubiquitous pathogen with monotherapeutic anti-pseudomonal agents. Worryingly, its genome plasticity contributes to the emergence of P. aeruginosa expressing different resistant phenotypes and is now responsible for notable epidemics within hospital settings. Considering this, we aimed to evaluate the synergistic combination of fortimicin with other traditional anti-pseudomonal agents and to analyze the resistome of pan-drug resistant (PDR) isolate. METHODS: Standard methods were used for analyzing the antimicrobial susceptibility tests. The checkerboard technique was used for the in vitro assessment of fortimicin antibiotic combinations against 51 MDR P. aeruginosa and whole genome sequencing was used to determine the resistome of PDR isolate. RESULTS: Out of 51 MDR P. aeruginosa, the highest synergistic effect was recorded for a combination of fortimicin with ß-lactam group as meropenem, ceftazidime, and aztreonam at 71%, 59% and 43%, respectively. Of note, 56.8%, 39.2%, and 37.2% of the tested MDR isolates that had synergistic effects were also resistant to meropenem, ceftazidime, and aztreonam, respectively. The highest additive effects were recorded for combining fortimicin with amikacin (69%) and cefepime (44%) against MDR P. aeruginosa. Resistome analysis of the PDR isolate reflected its association with the antibiotic resistance phenotype. It ensured the presence of a wide variety of antibiotic-resistant genes (ß-lactamases, aminoglycosides modifying enzymes, and efflux pump), rendering the isolate resistant to all clinically relevant anti-pseudomonal agents. CONCLUSION: Fortimicin in combination with classical anti-pseudomonal agents had shown promising synergistic activity against MDR P. aeruginosa. Resistome profiling of PDR P. aeruginosa enhanced the rapid identification of antibiotic resistance genes that are likely linked to the appearance of this resistant phenotype and may pave the way to tackle antimicrobial resistance issues shortly.

Molecular Mechanisms of Tumorgenesis and Metastasis of Long Non-coding RNA (lncRNA) NEAT1 in Human Solid Tumors; An Update.

The expression of the nuclear paraspeckle assembly transcript 1 (NEAT1), as a well-known long non-coding RNA (lncRNA), is often upregulated in varied types of cancers and associated with poor survival outcomes in patients suffering from tumors. NEAT1 promotes the tumors growth by influencing the various genes' expression profile that regulate various aspects of tumor cell behavior, in particular tumor growth, metastasis and drug resistance. This suggests that NEAT1 are capable of serving as a new diagnostic biomarker and target for therapeutic intervention. Through interrelation with enhancer of zeste homolog 2 (EZH2), NEAT1 acts as a scaffold RNA molecule, and thus regulating the expression EZH2-associated genes. Additionally, by perform as miRNA sponge, it constrains suppressing the interactions between miRNAs-mediated degradation of target mRNAs. In light of this, NEAT1 inhibition by small interfering RNA (siRNA) hampers tumorgenesis. We summarize recent findings about the expression, biological functions, and regulatory process of NEAT1 in human tumors. It specifically emphasizes the clinical significance of NEAT1 as a novel diagnostic biomarker and a promising therapeutic mark for many types of cancers.

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii.

Multidrug-resistant (MDR) pathogens are a rising global health worry that imposes an urgent need for the discovery of novel antibiotics particularly those of natural origin. In this context, we aimed to use the metagenomic nanopore sequence analysis of soil microbiota coupled with the conventional phenotypic screening and genomic analysis for identifying the antimicrobial metabolites produced by promising soil isolate(s). In this study, whole metagenome analysis of the soil sample(s) was performed using MinION™ (Oxford Nanopore Technologies). Aligning and analysis of sequences for probable secondary metabolite gene clusters were extracted and analyzed using the antiSMASH version 2 and DeepBGC. Results of the metagenomic analysis showed the most abundant taxa were Bifidobacterium, Burkholderia, and Nocardiaceae (99.21%, followed by Sphingomonadaceae (82.03%) and B. haynesii (34%). Phenotypic screening of the respective soil samples has resulted in a promising Bacillus isolate that exhibited broad-spectrum antibacterial activities against various MDR pathogens. It was identified using microscopical, cultural, and molecular methods as Bacillus (B.) haynesii isolate MZ922052. The secondary metabolite gene analysis revealed the conservation of seven biosynthetic gene clusters of antibacterial metabolites namely, siderophore lichenicidin VK21-A1/A2 (95% identity), lichenysin (100%), fengycin (53%), terpenes (100%), bacteriocin (100%), Lasso peptide (95%) and bacillibactin (53%). In conclusion, metagenomic nanopore sequence analysis of soil samples coupled with conventional screening helped identify B. haynesii isolate MZ922052 harboring seven biosynthetic gene clusters of promising antimicrobial metabolites. This is the first report for identifying the bacteriocin, lichenysin, and fengycin biosynthetic gene clusters in B. haynesii MZ922052.

Consensus-Based Expert Recommendations on the Management of Hemophilia A in the Gulf Region.

BACKGROUND: Hemophilia A presents a significant health challenge in the Gulf region, where it has an especially high prevalence. There are several unmet needs associated with the management of hemophilia A in the region. The aim of this manuscript was to contextualize unmet management needs, provide recommendations to optimize care, and specify requirements for the establishment of gene therapy centers in the region. SUMMARY: An expert panel was assembled comprising ten clinical hematologists from Kuwait, Oman, Saudi Arabia, and the UAE. The Delphi methodology was used to obtain a consensus on statements relating to several aspects of hemophilia A. A consensus was reached for all statements by means of an online, anonymized voting system. The consensus statements pertain to screening and diagnosis, treatment approaches, and requirements for the implementation of gene therapy. KEY MESSAGES: There are significant challenges that hinder the optimal management of hemophilia A in the Gulf region. The consensus statements presented provide specific recommendations to improve diagnostic and treatment approaches, promote multidisciplinary care, and optimize regional data generation and reporting. These statements also delineate the requirements for the establishment of gene therapy centers for hemophilia A in the region.