Molecular detection of exosomal miRNAs of blood serum for prognosis of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer affecting people. The discovery of new, non-invasive, specific, and sensitive molecular biomarkers for CRC may assist in the diagnosis and support therapeutic decision making. Exosomal miRNAs have been demonstrated in carcinogenesis and CRC development, which makes these miRNAs strong biomarkers for CRC. Deep sequencing allows a robust high-throughput informatics investigation of the types and abundance of exosomal miRNAs. Thus, exosomal miRNAs can be efficiently examined as diagnostic biomarkers for disease screening. In the present study, a number of 660 mature miRNAs were detected in patients diagnosed with CRC at different stages. Of which, 29 miRNAs were differentially expressed in CRC patients compared with healthy controls. Twenty-nine miRNAs with high abundance levels were further selected for subsequent analysis. These miRNAs were either highly up-regulated (e.g., let-7a-5p, let-7c-5p, let-7f-5p, let-7d-3p, miR-423-5p, miR-3184-5p, and miR-584) or down-regulated (e.g., miR-30a-5p, miR-99-5p, miR-150-5p, miR-26-5p and miR-204-5p). These miRNAs influence critical genes in CRC, leading to either tumor growth or suppression. Most of the reported diagnostic exosomal miRNAs were shown to be circulating in blood serum. The latter is a novel miRNA that was found in exosomal profile of blood serum. Some of the predicted target genes of highly expressed miRNAs participate in several cancer pathways, including CRC pathway. These target genes include tumor suppressor genes, oncogenes and DNA repair genes. Main focus was given to multiple critical signaling cross-talking pathways including transforming growth factor ß (TGFß) signaling pathways that are directly linked to CRC. In conclusion, we recommend further analysis in order to experimentally confirm exact relationships between selected differentially expressed miRNAs and their predicted target genes and downstream functional consequences.

Exosomes in Vascular/Neurological Disorders and the Road Ahead.

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided.

Prevalence of Adverse Pregnancy Outcomes in Women With and Without Gestational Diabetes Mellitus in Al-Baha Region, Saudi Arabia.

BACKGROUND: Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance that develops during pregnancy. It is associated with adverse maternal and fetal outcomes and has long-term health implications for both the mother and the child. This study aimed to estimate the prevalence of adverse pregnancy outcomes in women with and without GDM in the Al-Baha region, Saudi Arabia. METHODS: A cross-sectional study was conducted in the Al-Baha region from April 2023 to November 2023. The study included mothers residing in the Al-Baha region who were willing to participate and had access to a social media account. A simple random sampling technique was used, and the estimated sample size was 422. A self-administered electronic questionnaire was used to collect data on socio-demographic and lifestyle factors, as well as the pregnancy outcomes of diabetic and non-diabetic mothers. Descriptive and inferential statistical analyses were performed using IBM SPSS Statistics for Windows, Version 28.0 (Released 2012; IBM Corp., Armonk, New York, United States). RESULTS: We included 422 women in the study with the majority of participants in the age group of 36-40 years(15.4%, n=74). Most participants (66.6%, n=321) had attained a university degree, and a significant proportion resided in Al-Baha City (52.3%, n=252). Maternal outcomes indicated a significant association between GDM and the development of eclampsia (OR = 8.296, 95%CI: 4.353-15.810, p < 0.001), as well as an increased risk of thyroid diseases (OR = 2.723, 95%CI: 1.428-5.193, p = 0.002). Fetal outcomes revealed a significant association between GDM and respiratory distress/lack of oxygen in newborns (OR = 2.032, 95%CI: 1.085-3.805, p = 0.024), and infants of GDM patients had a higher risk of hypoglycemia (OR = 8.099, 95%CI: 3.350-19.581, p < 0.001). CONCLUSION: We found that GDM increased the risk of complications such as eclampsia, thyroid problems, and postpartum hemorrhage. GDM was also associated with shorter pregnancy durations, higher cesarean section rates, and an increased risk of developing type 2 diabetes post pregnancy. The study emphasized the importance of comprehensive GDM therapy and monitoring.

Awareness of Hepatitis B Virus (HBV) Screening Before Marriage and Pregnancy Among Adults in the Al-Baha Region, Saudi Arabia.

Background Hepatitis B is a global public health concern. Understanding the awareness, testing practices, and vaccination status of individuals is crucial for effective prevention and control strategies. This study aims to assess these aspects among participants in the Al-Baha region, Saudi Arabia. Methodology A cross-sectional study was conducted among 440 participants. Demographic data, awareness of hepatitis B, knowledge of transmission modes, symptoms, and complications were collected through a structured questionnaire. Participants' testing and screening practices, sources of information, and vaccination status were also assessed. Data were analyzed using descriptive statistics and associations were explored using chi-square tests. Results The majority of participants were females (51.8%) and aged 18-25 years (55.2%). While most participants had heard of hepatitis B (85.7%), only a small percentage correctly identified sexual contact as a mode of transmission (38.6%). Knowledge regarding symptoms and complications was moderate, with 52.3% correctly identifying symptoms and 69.8% recognizing liver damage and cirrhosis as complications. Although awareness of screening was high (84.8%), the actual practice was low (35.0%). Education was the least reported source of information, while the internet (46.7%) and health care provider (27.6%) were commonly mentioned. Approximately half of the participants reported receiving the hepatitis B vaccine (48.9%), but a significant proportion had not completed all vaccine doses (55.0%). Conclusion The study revealed moderate awareness of hepatitis B among the participants, but knowledge gaps existed regarding transmission modes and complete symptom recognition. Testing and screening practices were suboptimal, with low rates of screening despite high awareness. Vaccination uptake was moderate, but incomplete vaccine schedules were prevalent. Targeted educational campaigns are needed to address knowledge gaps, promote testing and completion of vaccination schedules, and enhance the role of healthcare providers in disseminating accurate information. Improving knowledge and practices related to hepatitis B can strengthen public health efforts, enhance prevention, and control strategies.

Outcomes of Operative Versus Nonoperative Management for Hallux Rigidus: A Tertiary Care Center Experience.

Background This study aims to investigate and report the outcomes of various management modalities used for hallux rigidus, a common form of degenerative joint disease affecting the foot and ankle. The research focuses on understanding the pathophysiology, classification systems, and nonoperative approaches such as medical therapy, intra-articular injections, shoe modifications, and physical therapy. Surgical techniques, including joint-sparing and joint-sacrificing procedures, are explored, considering factors such as disease stage and patient preferences. Methods A retrospective cohort study was conducted at King Abdulaziz Medical City (KAMC), Riyadh. The study included all patients who were diagnosed with hallux rigidus from the period 2016 to 2022. Data were collected through the BESTCare system at KAMC. All the data were collected through Microsoft Excel (Microsoft Corporation, Redmond, Washington) and transferred for analysis. Statistical analysis was performed using the IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York). Frequencies and percentages were used to detail categorical variables, whereas continuous variables were examined by the mean and standard deviation. A p-value of <0.05 was considered to report the statistical significance. Results A total of 84 patients were included. The majority were women (60.7%). Diabetes and hypertension were prevalent comorbidities, affecting 21.4% and 35.7% of patients, respectively. Nonoperative management was the most common approach (66.7%). Complications were minimal (2.4% infections, 1.2% metatarsalgia), and 67.9% of patients reported no persistence of symptoms after treatment. Conclusion The low complication rates and the lack of significant associations between treatment modalities and outcomes suggest the generally safe and effective nature of the employed interventions. These findings can guide clinicians in making informed decisions regarding the management of hallux rigidus, while also highlighting areas for further research to improve treatment strategies and outcomes.

Outcomes of Hallux Valgus Corrective Osteotomy: A Tertiary Hospital Experience.

BACKGROUND: A common form of forefoot deformity, hallux valgus (HV) is characterized by a prominent first metatarsal head, lateral deviation of the hallux, and medial deviation of the first metatarsal bone. In the case of HV, corrective osteotomies are performed with good results and patient satisfaction. METHODS: A retrospective cohort study of patients who underwent corrective osteotomy for hallux valgus from 2016 to 2022 was conducted at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Data were collected by chart review using the BestCARE system. IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, New York, United States) was used for statistical analysis. RESULTS: Our study included 166 patients. The mean age of the patients was found to be 41.3 years old and about 152 (91.6%) of them were females. The most frequently reported comorbidity was hypertension (10.2%). The mean hallux valgus angle was found to be 36.1 ± 9.9 and the mean intermetatarsal angle was found to be 15 ± 4.4 degrees. Seventy-six (45.8%) patients underwent nonoperative management first. The mean age at diagnosis among males was found to be 28.5 ± 11.3 years and among females was 37.9 ± 14.4 years; a significant difference between means was noted (p-value = 0.019) with mean age at diagnosis in males being significantly lesser than in females. CONCLUSION: Significant improvement and reduction were seen in HV angle post surgery. Nearly half of the patients underwent nonoperative management first. Age at diagnosis is significantly younger in males compared to females.

Studying the Association Between Knowledge of Professionalism and Demographic Characteristics in King Saud University Medical Students.

Objectives To study the association between the level of knowledge regarding professionalism and demographic characteristics among medical students from years three to five at King Saud University, Riyadh, Saudi Arabia. Methods Data for this quantitative observational cross-sectional study were collected using stratified random sampling. The participants included male and female students from years three to five studying at the College of Medicine, King Saud University. Data were collected using a self-administered questionnaire and analyzed using the Student's t-test and a one-way ANOVA test. Results The study comprised 112 female (52%) and 103 male (48%) students who completed 215 questionnaires. The mean percentage values of correct answers by females and males were 59.99% and 59.31%, respectively. Statistical analysis revealed no significant difference between the mean percentage of correct answers given by males and females (p=0.684). The mean percentage of correct answers among the 3rd, 4th, and 5th-year medical students was 59.27%, 56.56%, and 62.72%, respectively. Statistical analysis revealed significant differences between the academic year groups (p<0.05), and the grade point average (GPA) groups showed significant differences (p<0.05). Conclusion A highly significant association was found between knowledge of professionalism and both academic level and performance among medical students. This suggests that professional perception evolves parallel to acquiring basic science and clinical knowledge.

Cefoperazone targets D-alanyl-D-alanine carboxypeptidase (DAC) to control Morganella morganii-mediated infection: a subtractive genomic and molecular dynamics approach.

Morganella morganii is a Gram-negative bacterial pathogen that causes bacteremia, urinary tract infections, intra-abdominal infections, chorioamnionitis, neonatal sepsis, and newborn meningitis. To control this bacterial pathogen a total of 3565 putative proteins targets in Morganella morganii were screened using comparative subtractive analysis of biochemical pathways annotated by the KEGG that did not share any similarities with human proteins. One of the targets, D-alanyl-D-alanine carboxypeptidase DacB [Morganella] was observed to be implicated in the majority of cell wall synthesis pathways, leading to its selection as a novel pharmacological target. The drug that interacted optimally with the identified target was observed to be Cefoperazone (DB01329) with the estimated free energy of binding -8.9 Kcal/mol. During molecular dynamics simulations; it was observed that DB01328-2exb and DB01329-2exb complexes showed similar values as the control FMX-2exb complex near 0.2 nm with better stability. Furthermore, MMPBSA total free energy calculation showed better binding energy than the control complex for DB01329-2exb interaction i.e. -31.50 (±0.93) kcal/mol. Our presented research suggested that D-alanyl-D-alanine carboxypeptidase DacB could be a therapeutic target and cefoperazone could be a promising ligand to inhibit the D-alanyl-D-alanine carboxypeptidase DacB protein of Morganella morganii. To identify prospective therapeutic and vaccine targets in Morganella morganii, this is the first computational and subtractive genomics investigation of various metabolic pathways exploring other therapeutic targets of Morganella morganii. In vitro/in vivo experimental validation of the identified target D-alanyl-D-alanine carboxypeptidase and the design of its inhibitors is suggested to figure out the best dose, the drug's effectiveness, and its toxicity.Communicated by Ramaswamy H. Sarma.

Knowledge and Awareness About Gastric Cancer Among the General Population in Al-Baha City, Saudi Arabia.

Background Gastric cancer is a significant health concern worldwide, and its incidence varies across different populations. This study aimed to assess the level of knowledge and awareness of gastric cancer among the general population in Al-Baha City, Saudi Arabia.  Methodology This is a cross-sectional study that was conducted among the residents of Al-Baha city older than 18 years. The study was conducted based on a questionnaire that has been developed by a previous study. Data were initially recorded in an Excel sheet before being exported to the SPSS program, version 25 for data analysis. Results The survey included 426 respondents from Al-Baha city, Saudi Arabia, with 56.8% being females and the majority being in the age groups (21-30 years). Alcohol consumption (mean=4.5, SD= 0.77), smoking cigarettes or Shisha (mean= 4.38, SD=0.852), family history of gastric cancer (mean= 4, SD=1.008), a past medical history of gastric cancer (mean= 3.99, SD=0.911), stomach ulcer (mean=3.76, SD=0.898), and consumption of smoked food (mean= 3.69, SD=0.956) are the most widely recognized risk factors. The most highly recognized symptoms are gastrointestinal bleeding (mean= 4.03, SD=0.875), abdominal lump (mean= 3.94, SD=0.926), weight loss (mean= 3.93, SD=0.963), recurrent nausea and vomiting (mean=3.76, SD=0.956), and abdominal pain (mean= 3.57, SD=0.995). The study also identified several subgroups of the population that may benefit from targeted educational programs, including individuals in the age group of 41-50 years and those in non-medical occupations. Conclusion The study found that participants had a moderate level of knowledge about the risk factors and symptoms of gastric cancer, with significant variability among different subgroups of the population. Further research is needed to investigate the prevalence and risk factors of gastric cancer in Saudi Arabia and other similar populations, to develop effective prevention and management strategies for this disease.

Plant-Derived Extracellular Vesicles and Their Exciting Potential as the Future of Next-Generation Drug Delivery.

Plant cells release tiny membranous vesicles called extracellular vesicles (EVs), which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. These plant-derived EVs (PDEVs) are safe and easily extractable and have been shown to have therapeutic effects against inflammation, cancer, bacteria, and aging. They have shown promise in preventing or treating colitis, cancer, alcoholic liver disease, and even COVID-19. PDEVs can also be used as natural carriers for small-molecule drugs and nucleic acids through various administration routes such as oral, transdermal, or injection. The unique advantages of PDEVs make them highly competitive in clinical applications and preventive healthcare products in the future. This review covers the latest methods for isolating and characterizing PDEVs, their applications in disease prevention and treatment, and their potential as a new drug carrier, with special attention to their commercial viability and toxicological profile, as the future of nanomedicine therapeutics. This review champions the formation of a new task force specializing in PDEVs to address a global need for rigor and standardization in PDEV research.

Clinical outcomes of percutaneous screw fixation of acetabular fracture: A minimally invasive procedure.

Objective: Open reduction with internal fixation is the surgical intervention of choice for acetabular fractures (AFs). Percutaneous screw fixation for AFs is a new procedure that is desirable because of the complex anatomy of the pelvis. In this study, we aimed to assess the functional outcomes, mobility, healing, and distal neurovascular abnormalities in patients who underwent percutaneous retrograde screw fixation. Methods: Our study included 36 patients with AFs treated with percutaneous screw fixation between January 2016 and June 2021. There were 18 cases with anterior column AF, 7 cases with transverse AF, and 11 cases with associated AF, 6 of which had a T-shaped AF. Frequencies and percentages were used to describe characteristics and clinical outcomes. Mean and standard deviation were used for continuous variables. SPSS version 23 (IBM Corporation, Armonk, NY, USA) was used for statistical analysis. Results: The average time to regain full mobility with full weight bearing was 12.9 ± 5.4 weeks, and approximately 11.1 ± 2.8 weeks was required for patients to be pain-free with satisfactory fracture healing. Only a minority (8.3%) of patients had abnormalities affecting the distal neurovascular system, and 11.1% experienced sexual dysfunction. Pain severity was assessed with a visual analogue scale. The average pain severity on the first and third post-operative days was 4 ± 2.4 and 3.8 ± 2.6, respectively. However, the average pain intensity before discharge was 1.7 ± 2.6. Conclusion: Percutaneous screw fixation is the most efficient surgical choice for most pelvic/AFs.

Recognition of Differentially Expressed Molecular Signatures and Pathways Associated with COVID-19 Poor Prognosis in Glioblastoma Patients.

Glioblastoma (GBM) is a type of brain cancer that is typically very aggressive and difficult to treat. Glioblastoma cases have been reported to have increased during COVID-19. The mechanisms underlying this comorbidity, including genomic interactions, tumor differentiation, immune responses, and host defense, are not completely explained. Therefore, we intended to investigate the differentially expressed shared genes and therapeutic agents which are significant for these conditions by using in silico approaches. Gene expression datasets of GSE68848, GSE169158, and GSE4290 studies were collected and analyzed to identify the DEGs between the diseased and the control samples. Then, the ontology of the genes and the metabolic pathway enrichment analysis were carried out for the classified samples based on expression values. Protein-protein interactions (PPI) map were performed by STRING and fine-tuned by Cytoscape to screen the enriched gene module. In addition, the connectivity map was used for the prediction of potential drugs. As a result, 154 overexpressed and 234 under-expressed genes were identified as common DEGs. These genes were found to be significantly enriched in the pathways involved in viral diseases, NOD-like receptor signaling pathway, the cGMP-PKG signaling pathway, growth hormone synthesis, secretion, and action, the immune system, interferon signaling, and the neuronal system. STAT1, CXCL10, and SAMDL were screened out as the top 03 out of the top 10 most critical genes among the DEGs from the PPI network. AZD-8055, methotrexate, and ruxolitinib were predicted to be the possible agents for the treatment. The current study identified significant key genes, common metabolic signaling networks, and therapeutic agents to improve our perception of the common mechanisms of GBM-COVID-19.

25 (S)-Hydroxycholesterol acts as a possible dual enzymatic inhibitor of SARS-CoV-2 Mpro and RdRp-: an insight from molecular docking and dynamics simulation approaches.

The coronavirus disease (COVID-19) pandemic has rapidly extended globally and killed approximately 5.83 million people all over the world. But, to date, no effective therapeutic against the disease has been developed. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enters the host cell through the spike glycoprotein (S protein) of the virus. Subsequently, RNA-dependent RNA polymerase (RdRp) and main protease (Mpro) of the virus mediate viral transcription and replication. Mechanistically inhibition of these proteins can hinder the transcription as well as replication of the virus. Recently oxysterols and its derivative, such as 25 (S)-hydroxycholesterol (25-HC) has shown antiviral activity against SARS-CoV-2. But the exact mechanisms and their impact on RdRp and Mpro have not been explored yet. Therefore, the study aimed to identify the inhibitory activity of 25-HC against the viral enzymes RdRp and Mpro simultaneously. Initially, a molecular docking simulation was carried out to evaluate the binding activity of the compound against the two proteins. The pharmacokinetics (PK) and toxicity parameters were analyzed to observe the 'drug-likeness' properties of the compound. Additionally, molecular dynamics (MD) simulation was performed to confirm the binding stability of the compound to the targeted protein. Furthermore, molecular mechanics generalized Born surface area (MM-GBSA) was used to predict the binding free energies of the compound to the targeted protein. Molecular docking simulation identified low glide energy -51.0 kcal/mol and -35.0 kcal/mol score against the RdRp and Mpro, respectively, where MD simulation found good binding stability of the compound to the targeted proteins. In addition, the MM/GBSA approach identified a good value of binding free energies (ΔG bind) of the compound to the targeted proteins. Therefore, the study concludes that the compound 25-HC could be developed as a treatment and/or prevention option for SARS-CoV-2 disease-related complications. Although, experimental validation is suggested for further evaluation of the work.Communicated by Ramaswamy H. Sarma.

Computational Molecular Docking and Simulation-Based Assessment of Anti-Inflammatory Properties of Nyctanthes arbor-tristis Linn Phytochemicals.

The leaves, flowers, seeds, and bark of the Nyctanthes arbor-tristis Linn plant have been pharmacologically evaluated to signify the medicinal importance traditionally described for various ailments. We evaluated the anti-inflammatory potentials of 26 natural compounds using AutoDock 4.2 and Molecular Dynamics (MDS) performed with the GROMACS tool. SwissADME evaluated ADME (adsorption, distribution, metabolism, and excretion) parameters. Arb_E and Beta-sito, natural compounds of the plant, showed significant levels of binding affinity against COX-1, COX-2, PDE4, PDE7, IL-17A, IL-17D, TNF-α, IL-1ß, prostaglandin E2, and prostaglandin F synthase. The control drug celecoxib exhibited a binding energy of -9.29 kcal/mol, and among the tested compounds, Arb_E was the most significant (docking energy: -10.26 kcal/mol). Beta_sito was also observed with high and considerable docking energy of -8.86 kcal/mol with the COX-2 receptor. COX-2 simulation in the presence of Arb_E and control drug celecoxib, RMSD ranged from 0.15 to 0.25 nm, showing stability until the end of the simulation. Also, MM-PBSA analysis showed that Arb_E bound to COX-2 exhibited the lowest binding energy of -277.602 kJ/mol. Arb_E and Beta_sito showed interesting ADME physico-chemical and drug-like characteristics with significant drug-like effects. Therefore, the studied natural compounds could be potential anti-inflammatory molecules and need further in vitro/in vivo experimentation to develop novel anti-inflammatory drugs.

Identification and Characterization of Novel Mutations in Chronic Kidney Disease (CKD) and Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Saudi Subjects by Whole-Exome Sequencing.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population. Materials and Methods: In this study, 11 patients with chronic kidney disease were enrolled. The diagnosis of ADPKD was based on history and diagnostic images: CT images include enlargement of renal outlines, renal echogenicity, and presence of multiple renal cysts with dilated collecting ducts, loss of corticomedullary differentiation, and changes in GFR and serum creatinine levels. Next-generation whole-exome sequencing was conducted using the Ion Torrent PGM platform. Results: Of the 11 Saudi patients diagnosed with chronic kidney disease (CKD) and ADPKD, the most common heterozygote nonsynonymous variant in the PKD1 gene was exon15: (c.4264G > A). Two missense mutations were identified with a PKD1 (c.1758A > C and c.9774T > G), and one patient had a PKD2 mutation (c.1445T > G). Three detected variants were novel, identified at PKD1 (c.1758A > C), PKD2L2 (c.1364A > T), and TSC2 (deletion of a'a at the 3'UTR, R1680C) genes. Other variants in PKD1L1 (c.3813_381 4delinsTG) and PKD1L2 (c.404C > T) were also detected. The median age of end-stage renal disease for ADPK patients in Saudi Arabia was 30 years. Conclusion: This study reported a common variant in the PKD1 gene in Saudi patients with typical ADPKD. We also reported (to our knowledge) for the first time two novel missense variants in PKD1 and PKD2L2 genes and one indel mutation at the 3'UTR of the TSC2 gene. This study establishes that the reported mutations in the affected genes resulted in ADPKD development in the Saudi population by a median age of 30. Nevertheless, future protein−protein interaction studies to investigate the influence of these mutations on PKD1 and PKD2 functions are required. Furthermore, large-scale population-based studies to verify these findings are recommended.

Co-Occurrence of ß-Lactam and Aminoglycoside Resistance Determinants among Clinical and Environmental Isolates of Klebsiella pneumoniae and Escherichia coli: A Genomic Approach.

The presence of antimicrobial-resistance genes (ARGs) in mobile genetic elements (MGEs) facilitates the rapid development and dissemination of multidrug-resistant bacteria, which represents a serious problem for human health. This is a One Health study which aims to investigate the co-occurrence of antimicrobial resistance determinants among clinical and environmental isolates of K. pneumoniae and E. coli. Various bioinformatics tools were used to elucidate the bacterial strains' ID, resistome, virulome, MGEs, and phylogeny for 42 isolates obtained from hospitalized patients (n = 20) and environmental sites (including fresh vegetables, fruits, and drinking water) (n = 22). The multilocus sequence typing (MLST) showed that K. pneumoniae belonged to ten sequence types (STs) while the E. coli belonged to seventeen STs. Multidrug-resistant isolates harbored ß-lactam, aminoglycoside resistance determinants, and MGE were detected circulating in the environment (drinking water, fresh vegetables, and fruits) and in patients hospitalized with postoperative infections, neonatal sepsis, and urinary tract infection. Four K. pneumoniae environmental isolates (7E, 16EE, 1KE, and 19KE) were multidrug-resistant and were positive for different beta-lactam and aminoglycoside resistance determinants. blaCTX-M-15 in brackets of ISEc 9 and Tn 3 transposases was detected in isolates circulating in the pediatrics unit of Soba hospital and the environment. This study documented the presence of bacterial isolates harboring a similar pattern of antimicrobial resistance determinants circulating in hospitals and environments. A rapid response is needed from stakeholders to initiate a program for infection prevention and control measures to detect such clones disseminated in the communities and hospitals.

Whole-Genome Sequence of Multidrug-Resistant Methicillin-Resistant Staphylococcusepidermidis Carrying Biofilm-Associated Genes and a Unique Composite of SCCmec.

Staphylococcus epidermidis is part of the normal human flora that has recently become an important opportunistic pathogen causing nosocomial infections and tends to be multidrug-resistant. In this investigation, we aimed to study the genomic characteristics of methicillin-resistant S. epidermidis isolated from clinical specimens. Three isolates were identified using biochemical tests and evaluated for drug susceptibility. Genomic DNA sequences were obtained using Illumina, and were processed for analysis using various bioinformatics tools. The isolates showed multidrug resistance to most of the antibiotics tested in this study, and were identified with three types (III(3A), IV(2B&5), and VI(4B)) of the mobile genetic element SCCmec that carries the methicillin resistance gene (mecA) and its regulators (mecI and mecR1). A total of 11 antimicrobial resistance genes (ARGs) was identified as chromosomally mediated or in plasmids; these genes encode for proteins causing decreased susceptibility to methicillin (mecA), penicillin (blaZ), fusidic acid (fusB), fosfomycin (fosB), tetracycline (tet(K)), aminoglycosides (aadD, aac(6')-aph(2'')), fluoroquinolone (MFS antibiotic efflux pump), trimethoprim (dfrG), macrolide (msr(A)), and chlorhexidine (qacA)). Additionally, the 9SE strain belongs to the globally disseminated ST2, and harbors biofilm-formation genes (icaA, icaB, icaC, icaD, and IS256) with phenotypic biofilm production capability. It also harbors the fusidic acid resistance gene (fusB), which could increase the risk of device-associated healthcare infections, and 9SE has been identified as having a unique extra SCC gene (ccrB4); this new composite element of the ccr type needs more focus to better understand its role in the drug resistance mechanism.

The Therapeutic Potential of Milk Extracellular Vesicles on Colorectal Cancer.

Colorectal cancer remains one of the leading prevalent cancers in the world and is the fourth most common cause of death from cancer. Unfortunately, the currently utilized chemotherapies fail in selectively targeting cancer cells and cause harm to healthy cells, which results in profound side effects. Researchers are focused on developing anti-cancer targeted medications, which is essential to making them safer, more effective, and more selective and to maximizing their therapeutic benefits. Milk-derived extracellular vesicles (EVs) from camels and cows have attracted much attention as a natural substitute product that effectively suppresses a wide range of tumor cells. This review sheds light on the biogenesis, methods of isolation, characterization, and molecular composition of milk EVs as well as the therapeutic potentials of milk EVs on colorectal cancer.

Study of oral microbiota diversity among groups of families originally from different countries.

The diversity of oral microbiota is affected by diets habits, gender, age, ethnic group, and environment. The acquisition of oral microbiota and the role of family on oral microbiota development is poorly understood. This study aims to characterize and compare the oral bacterial microbiota among families using 16S rRNA gene sequencing. This work was conducted in Jeddah city from 2020 to 2021, in which four families composed of 20 members of different ethnicity and lifestyle were recruited. After the collection of saliva samples, the DNA was extracted and processed for 16S rRNA gene metagenomics sequencing. Among 378 OUTs generated, 39 (10.3%) were unique in group A, 13 (3.4%) unique in group B, and 11 (2.9%) were unique in groups C and D. We observed a significant variation at the level of top abundance phylum (14), families (23), genera (24), and species (22) of bacteria among family members. Within family groups, different bacterial species were reported to be more dominant among certain family members than the other; Prevotella melaninogenica, Prevotella histicola and Haemophilus parainfluenzae, Veillonella atypica, Porphyromonas pasteri and Haemophilus pittmaniae were more dominant in parents of some families than the other family member. In summary, this study highlights the precise and perceptible association of oral microbial between family members. Our findings documented the clustering of certain bacterial species in family groups, supporting the role of community in the development of oral microbiota.

Genomic Analysis of Multidrug-Resistant Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae Strain Lacking the Hypermucoviscous Regulators (rmpA/rmpA2).

Hypervirulent K. pneumoniae (hvKP) strains possess distinct characteristics such as hypermucoviscosity, unique serotypes, and virulence factors associated with high pathogenicity. To better understand the genomic characteristics and virulence profile of the isolated hvKP strain, genomic data were compared to the genomes of the hypervirulent and typical K. pneumoniae strains. The K. pneumoniae strain was isolated from a patient with a recurrent urinary tract infection, and then the string test was used for the detection of the hypermucoviscosity phenotype. Whole-genome sequencing was conducted using Illumina, and bioinformatics analysis was performed for the prediction of the isolate resistome, virulome, and phylogenetic analysis. The isolate was identified as hypermucoviscous, type 2 (K2) capsular polysaccharide, ST14, and multidrug-resistant (MDR), showing resistance to ciprofloxacin, ceftazidime, cefotaxime, trimethoprim-sulfamethoxazole, cephalexin, and nitrofurantoin. The isolate possessed four antimicrobial resistance plasmids (pKPN3-307_type B, pECW602, pMDR, and p3K157) that carried antimicrobial resistance genes (ARGs) (blaOXA-1,blaCTX-M-15, sul2, APH(3″)-Ib, APH(6)-Id, and AAC(6')-Ib-cr6). Moreover, two chromosomally mediated ARGs (fosA6 and SHV-28) were identified. Virulome prediction revealed the presence of 19 fimbrial proteins, one aerobactin (iutA) and two salmochelin (iroE and iroN). Four secretion systems (T6SS-I (13), T6SS-II (9), T6SS-III (12), and Sci-I T6SS (1)) were identified. Interestingly, the isolate lacked the known hypermucoviscous regulators (rmpA/rmpA2) but showed the presence of other RcsAB capsule regulators (rcsA and rcsB). This study documented the presence of a rare MDR hvKP with hypermucoviscous regulators and lacking the common capsule regulators, which needs more focus to highlight their epidemiological role.