Search

The human microbiome is a complex ecosystem of bacteria residing in the body. It plays a crucial role in safeguarding the overall well-being of individuals while also making them more vulnerable to various diseases. The human microbiota, genetics, and health have a complex connection, which is significant for maintaining health and preventing infections. The microbiome has a role in several gastrointestinal, skin, dental, and systemic diseases, such as obesity, diabetes, and autoimmune disorders. Genetic variation and lifestyle and dietary choices modify the microbiome composition, thereby influencing the risk of developing severe infections. The microbiome impacts host gene expression and acts as a biomarker for several diseases. The gut microbiome and genes are linked in the pathogenesis of obesity and inflammatory bowel disease. Therefore, this review focuses on the relationship between the microbiome and genetics and elucidation of the complexity of this connection. Future research-based microbiome interventions to prevent diseases could lead to strategies for personalized medicine that enhance treatment efficacy and health outcomes.

Naegleria fowleri is a rare but deadly pathogen that has emerged as an important global public health concern. The pathogen induces primary amoebic meningoencephalitis (PAM), a rapidly progressive and almost always fatal life-threatening brain infection. The devastating impact of N. fowleri and the high mortality rate underscores a deeper understanding and the development of innovative strategies to tackle this issue. Despite various studies that have been conducted on N. fowleri, a comprehensive review that integrates recent findings and addresses critical gaps in understanding remains lacking. This review provides a detailed overview of N. fowleri epidemiology, transmission dynamics, phylogenetic diversity, state-of-the-art diagnostic techniques, therapeutic approaches, and preventive measures. We identified 488 PAM cases globally, reported since 1962, with the highest numbers in the US, Pakistan, and Australia. A phylogenetic analysis of 41 N. fowleri ITS-1, 5.8S, ITS-2 region-based sequences showed genotypic diversity, with genotypes II and III being the most prevalent in Asia, North America, and Europe. Effective approaches to preventing N. fowleri transmission include applying free chlorine to water in storage tanks, taking precautions while swimming, and performing ablution with sterilized water (e.g., boiled or distilled) while avoiding deep inhalation of water, especially in regions with high water contamination. This review highlights the global impact of N. fowleri, future surveillance strategies, prompt diagnosis, potential therapeutic options, and vaccine development to prevent PAM outbreaks. It highlights the importance of joint government and public health efforts to combat this deadly pathogen.

Cytokine storm (CS) refers to the spontaneous dysregulated and hyper-activated inflammatory reaction occurring in various clinical conditions, ranging from microbial infection to end-stage organ failure. Recently the novel coronavirus involved in COVID-19 (Coronavirus disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been associated with the pathological phenomenon of CS in critically ill patients. Furthermore, critically ill patients suffering from CS are likely to have a grave prognosis and a higher case fatality rate. Pathologically CS is manifested as hyper-immune activation and is clinically manifested as multiple organ failure. An in-depth understanding of the etiology of CS will enable the discovery of not just disease risk factors of CS but also therapeutic approaches to modulate the immune response and improve outcomes in patients with respiratory diseases having CS in the pathogenic pathway. Owing to the grave consequences of CS in various diseases, this phenomenon has attracted the attention of researchers and clinicians throughout the globe. So in the present manuscript, we have attempted to discuss CS and its ramifications in COVID-19 and other respiratory diseases, as well as prospective treatment approaches and biomarkers of the cytokine storm. Furthermore, we have attempted to provide in-depth insight into CS from both a prophylactic and therapeutic point of view. In addition, we have included recent findings of CS in respiratory diseases reported from different parts of the world, which are based on expert opinion, clinical case-control research, experimental research, and a case-controlled cohort approach.

AbstractA novel coronavirus strain called SARS-CoV-2 first appeared in China in December 2019. Natural products are significant sources of prospective and new antiviral medications, and new antiviral drug research has advanced significantly in recent years. The current study allows us to select specific components of olive oil that are thought to be anti-SARS-CoV-2 and assess their impact on SARS-CoV-2 in vitro. The 26 compounds of olive oil were obtained from the PubChem database and docked against the RdRP of SARS-CoV-2 (pdb id: 6XQB) by autodock vina 1 1 2 linux x86 software. Cytotoxicity and antiviral activity were measured by the MTT assay protocol (the crystal violet method). The findings revealed that the range of the olive oil compound’s molecular docking binding affinity score against the RdRP SARS-CoV-2 target was 5.9–18.2 kcal/mol. The best compound is apigenin since it has a low energy value of −18.2 kcal/mol, followed by taxifolin, which has an energy value of −14.2 kcal/mol. On the other hand, the molecule with the lowest energy is believed to be the good one. Additionally, Lipinski’s criteria and AD-MET analysis supported the created apigenin and taxifolin’s status as a secure pharmaceutical substance. Also, apigenin and taxifolin showed moderate antiviral effectiveness against SARS-CoV-2 in vitro, with SI values of 9.7 and 8.79, respectively, compared with olive oil’s crude SI value of 9.57. According to our results, we think that olive oil is an essential source of cutting-edge SARS-CoV-2 antiviral drugs, especially apigenin and taxifolin compounds.

Abstract Background Extensively drug-resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) poses a grave threat to public health due to increased mortality and morbidity caused by typhoid fever. Honey is a promising antibacterial agent, and we aimed to determine the antibacterial activity of honey against XDR S. Typhi. Methods We isolated 20 clinical isolates of XDR S. Typhi from pediatric septicemic patients and determined the minimum inhibitory concentrations (MICs) of different antibiotics against the pathogens using the VITEK 2 Compact system. Antimicrobial-resistant genes carried by the isolates were identified using PCR. The antibacterial efficacy of five Pakistani honeys was examined using agar well diffusion assay, and their MICs and minimum bactericidal concentrations (MBCs) were determined with the broth microdilution method. Results All 20 isolates were confirmed as S. Typhi. The antibiogram phenotype was confirmed as XDR S. Typhi with resistance to ampicillin (≥ 32 µg/mL), ciprofloxacin (≥ 4 µg/mL), and ceftriaxone (≥ 4 µg/mL) and sensitivity to azithromycin (≤ 16 µg/mL) and carbapenems (≤ 1 µg/mL). Molecular conformation revealed the presence of bla TM-1 , Sul1, qnrS, gyrA, gyrB, and bla CTX-M-15 genes in all isolates. Among the five honeys, beri honey had the highest zone of inhibition of 7–15 mm and neem honey had a zone of inhibition of 7–12 mm. The MIC and MBC of beri honey against 3/20 (15%) XDR S. Typhi isolates were 3.125 and 6.25%, respectively, while the MIC and MBC of neem were 3.125 and 6.25%, respectively, against 3/20 (15%) isolates and 6.25 and 12.5%, respectively, against 7/20 (35%) isolates. Conclusion Indigenous honeys have an effective role in combating XDR S. Typhi. They are potential candidates for clinical trials as alternative therapeutic options against XDR S. Typhi isolates.

As per a recent study conducted by the WHO, 15.4% of all cancers are caused by infectious agents of various categories, and more than 10% of them are attributed to viruses. The emergence of COVID-19 has once again diverted the scientific community’s attention toward viral diseases. Some researchers have postulated that SARS-CoV-2 will add its name to the growing list of oncogenic viruses in the long run. However, owing to the complexities in carcinogenesis of viral origin, researchers across the world are struggling to identify the common thread that runs across different oncogenic viruses. Classical pathways of viral oncogenesis have identified oncogenic mediators in oncogenic viruses, but these mediators have been reported to act on diverse cellular and multiple omics pathways. In addition to viral mediators of carcinogenesis, researchers have identified various host factors responsible for viral carcinogenesis. Henceforth owing to viral and host complexities in viral carcinogenesis, a singular mechanistic pathway remains yet to be established; hence there is an urgent need to integrate concepts from system biology, cancer microenvironment, evolutionary perspective, and thermodynamics to understand the role of viruses as drivers of cancer. In the present manuscript, we provide a holistic view of the pathogenic pathways involved in viral oncogenesis with special emphasis on alteration in the tumor microenvironment, genomic alteration, biological entropy, evolutionary selection, and host determinants involved in the pathogenesis of viral tumor genesis. These concepts can provide important insight into viral cancers, which can have an important implication for developing novel, effective, and personalized therapeutic options for treating viral cancers.

Soil contamination with cobalt (Co) negatively impacts plant growth and production. To combat Co toxicity, plant growth-promoting microorganisms for improving plant growth are effectively applied. To this end, unclassified haloarchaeal species strain NRS_31 (OL912833), belonging to Haloferax genus, was isolated, identified for the first time, and applied to mitigate the Co phytotoxic effects on maize plants. This study found that high Co levels in soil lead to Co accumulation in maize leaves. Co accumulation in the leaves inhibited maize growth and photosynthetic efficiency, inducing oxidative damage in the tissue. Interestingly, pre-inoculation with haloarchaeal species significantly reduced Co uptake and mitigated the Co toxicity. Induced photosynthesis improved sugar metabolism, allocating more carbon to defend against Co stress. Concomitantly, the biosynthetic key enzymes involved in sucrose (sucrose-P-synthase and invertases) and proline (pyrroline-5- carboxylate synthetase (P5CS), pyrroline-5-carboxylate reductase (P5CR)) biosynthesis significantly increased to maintain plant osmotic potential. In addition to their osmoregulation potential, soluble sugars and proline can contribute to maintaining ROS hemostasis. Maize leaves managed their oxidative homeostasis by increasing the production of antioxidant metabolites (such as phenolics and tocopherols) and increasing the activity of ROS-scavenging enzymes (such as POX, CAT, SOD, and enzymes involved in the AsA/GSH cycle). Inside the plant tissue, to overcome heavy Co toxicity, maize plants increased the synthesis of heavy metal-binding ligands (metallothionein, phytochelatins) and the metal detoxifying enzymes (glutathione S transferase). Overall, the improved ROS homeostasis, osmoregulation, and Co detoxification systems were the basis underlying Co oxidative stress, mitigating haloarchaeal treatment's impact.

Hypervirulent Klebsiella pneumoniae (hvKp) is a new emerging variant of K. pneumoniae that is increasingly reported worldwide. The variant hvKp is known to cause severe invasive community-acquired infections such as metastatic meningitis, pyogenic liver abscesses (PLA) and endophthalmitis, but its role in hospital-acquired infections (HAIs) is little known. The aim of this study was to evaluate the prevalence of hvKp among hospital-acquired (HA) K. pneumoniae infections in the intensive care unit (ICU) and to compare between hvKp and classical K. pneumoniae (cKP) regarding antimicrobial resistance pattern, virulence and molecular characteristics. The study was cross-sectional and included 120 ICU patients suffering from HA K. pneumoniae infections between January and September 2022. K. pneumoniae isolates were subjected to antimicrobial susceptibility testing and detection of extended-spectrum-β-lactamase (ESBL) production by the Phoenix 100 automated microbiology system, string test, biofilm formation, serum resistance assay, and detection of virulence-associated genes (rmpA, rmpA2, magA, iucA) and capsular serotype-specific genes (K1, K2, K5, K20, K57) by polymerase chain reaction (PCR). Of 120 K. pneumoniae isolates, 19 (15.8%) were hvKp. The hypermucoviscous phenotype was more significantly detected in the hvKp group than in the cKP group (100% vs. 7.9%, p ≤ 0.001). The rate of resistance to different antimicrobial agents was significantly higher in the cKP group than that in the hvKp group. Fifty-three strains were identified as ESBL-producing strains, which was more frequent in the cKP group than in the hvKp group (48/101 [47.5%] vs. 5/19 [26.3%], respectively, p ≤ 0.001). The hvKP isolates were highly associated with moderate and strong biofilm formation than cKP isolates (p = 0.018 and p = 0.043 respectively). Moreover, the hvKP isolates were highly associated with intermediate sensitivity and re sistance to serum in the serum resistance assay (p = 0.043 and p = 0.016 respectively). K1, K2, rmpA, rmpA2, magA and iucA genes were significantly associated with hvKp (p ≤ 0.001, 0.004, K5, K20 and K57 were not associated with hvKp. The hvKp strains have emerged as a new threat to ICU patients because of their ability to cause more severe and life-threatening infections than cKP. The string test alone as a laboratory test for screening of hvKp has become insufficient. Recently, hvKp was defined as hypermucoviscous- and aerobactin-positive. It is important to improve the awareness towards the diagnosis and management of hvKp infections.

Antibiotic-resistant bacteria causing foodborne serious illnesses can be found in contaminated food. Therefore, this study aimed to identify the pathogens, genes, and antimicrobial residues present in raw milk and meat. We collected 40 raw milk and 40 beef samples using the aseptic method from various parts of the Faisalabad metropolis, Pakistan. The samples were cultured on blood, MacConkey, and UTI chrome agar. The VITEK 2 compact system was used for microbial identification and determination of minimum inhibitory concentrations. Antimicrobial resistance genes for extended-spectrum β-lactamases, methicillin resistance in Staphylococcus aureus, and carbapenem resistance were identified using molecular techniques. ELISA was used to determine the tetracycline residue level in each sample. The beef samples showed polymicrobial contamination with 64 bacterial isolates, with Escherichia coli (29; 45.3%) and Klebsiella pneumoniae (11; 17.1%) predominating. The milk samples showed polymicrobial contamination with 73 bacterial isolates, with E. coli (22; 30%), K. pneumoniae (12; 16.4%), and S. aureus (10; 13.6%) forming the majority. Twenty-eight (43.7%) isolates from beef harbored tet genes, nineteen (29.6%) blaCTX-M, and fourteen (21.8%) blaNDM-1, and twenty-six (35.6%) isolates from milk harbored tet genes, nineteen (26%) blaTEM and blaCTX-M, and three (4%) blaNDM-1. Twenty-two (55%) each of the beef and milk samples exceeded the maximum residue limit for tetracycline. Polymicrobial contamination by bacteria possessing blaCTX-M, blaTEM, blaNDM-1, blaOXA, mecA, and tet genes was identified in food samples. The high tetracycline residue levels pose a serious health risk to consumers.

Coronavirus disease-2019 is currently causing a world pandemic. The Kingdom of Saudi Arabia (KSA) reported its first case on March 2, 2020. Due to its potential rapid dissemination within the public and a large probability of a countrywide outbreak, along with the country's experience in battling another similar coronavirus (the Middle East respiratory syndrome–coronavirus), the KSA was among the leading bodies in the world for its swift community action and hospital preparedness.

Background: The Kingdom of Saudi Arabia (KSA) reported 170,639 cases and 1430 deaths from COVID-19 since the first case emerged in the country on March 2 through June 25, 2020. The objective of this report is to describe the characteristics and outcome observed among 99 hospitalized COVID-19 patients in the largest academic hospital in KSA, and assess co-infection with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Methods: This single-center case series data included select epidemiological, clinical, radiological features and laboratory findings of all confirmed hospitalized cases of COVID-19 in King Saud University Medical City (KSUMC), Riyadh, KSA, from March 22 until May 31, 2020, followed through June 6, 2020. We conducted retrospective analysis of listed data from 99 hospitalized patients and present characteristics and factors associated with severity in percentages and univariate odds ratios. Cases were confirmed using nasopharyngeal or throat swab by real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and MERS-CoV by RT-PCR. Results: The 99 hospitalized COVID-19 patients included in this analysis constitute 16% of 632 positive SARS-CoV-2 among 6633 persons who were tested at the KSUMC (positivity rate, 9.4%). MERS-CoV PCR was negative in all 99 patients tested. The majority of these 99 hospitalized patients were males (66%), had a mean age of 44 years (range, 19–87), and a quarter (25.3%) were health care workers. Patients with comorbid conditions accounted for 52.5% of patients including the 8.1% who were asymptomatic; diabetes mellitus being the most frequent (31.3%), followed by hypertension (22.2%). The most common presenting symptoms were fever (67.7%), cough (60.6%), dyspnea (43.4%), upper respiratory symptoms (27.3%), fatigue (26.3%), diarrhea (19.2%) and loss of smell (9.1%). The clinical conditions among these 99 patients included upper respiratory tract infection (47.5%), abnormal chest X-ray, lymphopenia, high inflammatory markers a fifth (21%) of patients had moderate pneumonia, while 7% had severe pneumonia with 22.2% requiring admission to the intensive care unit and 12.1% died. Late presentation with severe disease, an abnormal chest X-ray, lymphopenia, high inflammatory markers (C-reactive protein, ferritin, and procalcitonin), and end organ damage (high creatinine or high aspartate aminotransferase) were predictors for admission to critical care unit or died. Conclusion: We observed no MERS-CoV co-infection in this early cohort of hospitalized COVID-19 patients who were relatively young, more than half had comorbid conditions, presented with fever and/or cough, an abnormal chest X-ray, lymphopenia, and high inflammatory markers. Given MERS-CoV endemicity in the country, co-monitoring of MERS-CoV and SARS-CoV-2 coinfection is critical.

A strain of Bacillus cereus was isolated from the Saudi Red Sea coast and identified based on culture features, biochemical characteristics, and phylogenetic analysis of 16S rRNA sequences. EPSR3 was a major fraction of exopolysaccharides (EPS) containing no sulfate and had uronic acid (28.7%). The monosaccharide composition of these fractions is composed of glucose, galacturonic acid, and arabinose with a molar ratio of 2.0: 0.8: 1.0, respectively. EPSR3 was subjected to antioxidant, antitumor, and anti-inflammatory activities. The results revealed that the whole antioxidant activity was 90.4 ± 1.6% at 1500 µg/mL after 120 min. So, the IC50 value against DPPH radical found about 500 µg/mL after 60 min. While using H2O2, the scavenging activity was 75.1 ± 1.9% at 1500 µg/mL after 60 min. The IC50 value against H2O2 radical found about 1500 µg/mL after 15 min. EPSR3 anticytotoxic effect on the proliferation of (Bladder carcinoma cell line) (T-24), (human breast carcinoma cell line) (MCF-7), and (human prostate carcinoma cell line) (PC-3) cells. The calculated IC50 for cell line T-24 was 121 ± 4.1 µg/mL, while the IC50 for cell line MCF-7 was 55.7 ± 2.3 µg/mL, and PC-3 was 61.4 ± 2.6 µg/mL. Anti-inflammatory activity was determined for EPSR3 using different methods as Lipoxygenase (LOX) inhibitory assay gave IC50 12.9 ± 1.3 µg/mL. While cyclooxygenase (COX-2) inhibitory test showed 29.6 ± 0.89 µg /mL. EPSR3 showed potent inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci. The exposure times of EPSR3 for the complete inhibition of cell viability of methicillin resistant S. aureus was found to be 5% at 60 min. Membrane stabilization inhibitory gave 35.4 ± 0.67 µg/mL. EPSR3 has antitumor activity with a reasonable margin of safety. The antitumor activity of EPSR3 may be attributed to its content from uronic acids with potential for cellular antioxidant and anticancer functional properties.

The HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus, Tat–TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat–TAR RNA interaction, we used a crystal structure of acetylpromazine bound to the bulge of TAR RNA, to dock compounds from the Enamine database containing over two million individual compounds. The docking procedure identified 173 compounds that were further analyzed for the inhibition of HIV-1 infection. The top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50 = 2.97 μM), T0516-4834 (IC50 = 0.2 μM) and T5628834 (IC50 = 3.46 μM), were further tested for HIV-1 transcription inhibition. Only the T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas the T6780107 compound inhibited equally basal and Tat-induced transcription and the T5628834 compound only inhibited basal HIV-1 transcription. The compounds were tested for the inhibition of translation and showed minimal (

The Kingdom of Saudi Arabia (KSA) is an Islamic monarchy and was established in 1932. Saudi women first entered the medical field in 1975 and the country has since seen a steady increase in women pursuing medicine. However, there is limited data on gender related issues for women doctors practicing in Saudi Arabia. Therefore, our study objective was to assess the perception amongst peers regarding gender equality and social issues faced by women doctors in Saudi Arabia. An online anonymous cross-sectional survey was administered in English to doctors at King Khalid Hospital, affiliated to King Saud University, in Riyadh, between April and May of 2016. Of 1015 doctors, 304 (30%) participated, of which 129 (42.4%) were females and 231 (76%) were Saudi nationals. The average age was 32.4 years (±SD: 8.7). The majority opined that there was no gender discrimination in salaries (73.7% p-value = 0.4), hospital benefits (62.2% p-value = 0.06) or entry into any field of Medicine/Pediatrics (68.4% p-value = 0.207). However, only a minority believed that there was no gender discrimination for entry into surgery (37.3% p-value = .091). A higher proportion of male doctors agreed that promotion opportunities are equal (66.3% vs 45.7%, p-value = 0.002). However, of 54 consultants, only 18 (33.3%) were women. Over half of the women (52.3%) reported that they never wear the face veil. Only a minority of male and female doctors (12.2%) believed women doctors should wear the veil since they examine male patients. Fewer respondents believed that female doctors face harassment from male doctors (14.5%) whereas 30.7% believed female doctors face harassment from male patients. More females, than males, agreed with the statement that female doctors are as committed to their careers as are males (92.2% vs 67.4%, p-value