Pomegranate peel extract is an effective agent against MDR bacteria.

Multidrug-resistant (MDR) bacteria are one of the major public health threats facing humanity. Infections with MDR strains are difficult or impossible to treat with standard antibiotics leading to severe illnesses and even deaths. The spread of MDR bacteria has necessitated the search for alternative approaches that tackle MDR pathogens. Natural plants can be utilized as alternative therapeutic agents against the rise of MDR bacteria. In this study, we aimed to assess the antimicrobial activity of pomegranate peel extracts (PPE) against MDR clinical isolates. A total of 9 clinical isolates (8 MDR and 1 non-MDR clinical isolates) were collected and examined for their susceptibility to PPE. Using the zone of inhibition assay, 4 isolates (S. aureus, three MRSA isolates, Vancomycin-resistant Enterococci (VRE), and Acinetobacter baumannii) were sensitive to PPE. In Broth assay, 4 mg/ml PPE significantly reduced the growth (S. aureus, three MRSA isolates, Vancomycin-resistant Enterococci (VRE), and Acinetobacter baumannii), while 40 mg/ml PPE either significantly reduced or completely inhibited the growth of the isolates. The minimum bactericidal concentration (MBC) of PPE against S. aureus and MRSA-88 was 10 mg/ml. This study showed the potential of PPE as an alternative compound for treating infections caused by PPE-sensitive MDR bacteria.

Detection of chikungunya virus in the Southern region, Saudi Arabia.

BACKGROUND AND AIM: Despite the fact that the chikungunya viral infection is a neglected disease, complications such as hemorrhagic fever, arthritis, and lymphopenia remain a health concern. The aim of this study was to determine the prevalence of the chikungunya virus in the Southern Region, Saudi Arabia. Enzyme immunoassay and polymerase chain reaction have been compared between samples. MATERIALS AND METHODS: Forty samples from two southern hospitals in Saudi Arabia were collected between December 2019 and February 2020 and screened for chikungunya virus IgG antibodies and for viral RNA. Selection criteria were based on hematological parameters and rheumatological profiles such as rheumatoid factor, c-reactive protein, anti-nuclear antibody, and anti-cyclic citrullinated peptide (anti-CCP) of out-patients. RESULTS: One confirmed case of chikungunya virus was detected using the ELISA test. However, no viral RNA was detected in any of the samples. This suggests that the virus is cleared rapidly in patients. CONCLUSION: Chikungunya is a neglected viral disease in Saudi Arabia. Future work should focus on detailed investigation of this viral infection and its vectors.

Physcion Induces Hemolysis and Premature Phosphatidylserine Externalization in Human Erythrocytes.

The prevalence of cancer-associated anemia (CIA) is high, and the mechanisms governing its development remain poorly understood. Eryptosis, the suicidal cell death of red blood cells (RBCs), may account for CIA as it is triggered by clinically approved chemotherapeutics including cisplatin and paclitaxel. Physcion (PSN), an anthraquinone extracted from rhubarb and other plants, has shown great promise as an anticancer agent. However, the potential toxicity of PSN to RBCs remains elusive. RBCs were isolated from heparinized blood, and incubated with 10-100 µM of PSN for 24 h at 37 °C. Hemolysis was photometrically calculated from hemoglobin concentration in the medium at 405 nm, while flow cytometry was employed to investigate cardinal markers of eryptosis. Phosphatidylserine (PS) exposure was detected by Annexin-V-fluorescein isothiocyanate (FITC), intracellular calcium by Fluo4/AM, cellular volume from forward scatter (FSC), and oxidative stress by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). PSN induced overt hemolysis at 50 and 100 µM which was not mediated through calcium influx, protein kinase C, casein kinase 1α, or receptor-interacting protein 1. Moreover, PSN caused significant increase in Annexin-V-FITC and Fluo4 fluorescence with no appreciable influence on FSC or DCF values. Accordingly, PSN stimulates premature eryptosis characterized by PS externalization and intracellular calcium overload without cell shrinkage or oxidative damage. In conclusion, this report shows, for the first time, that PSN is cytotoxic to RBCs by inducing hemolysis and programmed cell death which may limit its success as a chemotherapeutic agent.

The potential impact of digital economy on energy poverty in the context of Chinese provinces.

This study focused on exploring the impact of the digital economy (DE) on energy poverty (EP) across Chinese provinces from 2004 to 2018, motivated by the critical need to understand how technological advancements in the digital sector influence energy accessibility and sustainability. Conducted against the backdrop of global digital transformation, the research aimed to dissect the nuanced ways in which the DE contributes to mitigating EP, employing dynamic panel threshold and indirect effect models to capture both the direct and nuanced, and intermediate effects of digital progress on energy deprivation. Key findings revealed a significant reduction in EP attributed to the advancements in DE, with the most notable improvements observed in Eastern China where strategic energy policies and management practices enhanced the positive impacts of digitalization. The study highlighted the DE's role in improving energy access, efficiency, and environmental sustainability, although it also pointed out the potential for regressive effects in areas with lower levels of technological advancement. These findings are of substantial value as they offer empirical evidence of the DE's capacity to alleviate EP, underlining the importance of integrating digital strategies into energy policy planning. The research provides critical insights for policymakers, stakeholders in the energy sector, and scholars interested in the synergies between digital innovation and energy security, suggesting that leveraging digital technologies could accelerate efforts towards achieving sustainable energy access and combating energy poverty in China and potentially in other contexts facing similar challenges.

Genomic Insight of Leishmania Parasite: In-Depth Review of Drug Resistance Mechanisms and Genetic Mutations.

Leishmaniasis, which is caused by a parasitic protozoan of the genus Leishmania, is still a major threat to global health, impacting millions of individuals worldwide in endemic areas. Chemotherapy has been the principal method for managing leishmaniasis; nevertheless, the evolution of drug resistance offers a significant obstacle to therapeutic success. Drug-resistant behavior in these parasites is a complex phenomenon including both innate and acquired mechanisms. Resistance is frequently related to changes in drug transportation, drug target alterations, and enhanced efflux of the drug from the pathogen. This review has revealed specific genetic mutations in Leishmania parasites that are associated with resistance to commonly used antileishmanial drugs such as pentavalent antimonials, miltefosine, amphotericin B, and paromomycin, resulting in changes in gene expression along with the functioning of various proteins involved in drug uptake, metabolism, and efflux. Understanding the genetic changes linked to drug resistance in Leishmania parasites is essential for creating approaches for tackling and avoiding the spread of drug-resistant variants. Based on which specific treatments focus on mutations and pathways could potentially improve treatment efficacy and help long-term leishmaniasis control. More study is needed to uncover the complete range of genetic changes generating medication resistance and to develop new therapies based on available information.

Risk surveillance with spatial distribution of Organochlorine Pesticides (OCPs) from sedimentary samples of Chenab River.

A pioneering study employed a holistic geostatistical approach to predict the spatial variability of a non sampled area in the Chenab River, Pakistan, using kriging interpolation for organochlorine pesticide (OCP)-polluted risk zones. The Present research intended to investigate the carcinogenic and non-carcinogenic human health risks, contamination levels, and spatial variation of OCPs in the Chenab River, Pakistan. The residual OCP content in sediment samples (n = 120) ranged from 0.056 to 32.14 ng/g. DDE and α-HCH were prevalent among all the samples analyzed, with mean concentrations of 15.84 ± 8.02 and 12.45 ± 6.72 ng/g, respectively. The order of magnitude of OCPs in sediment samples was DDTs > α-HCH > chlorothalonil > heptachlor > endosulfan > aldrin > dieldrin. The findings of the single (SPI) and Nemerow (Nel) pollution index of α-HCH, heptachlor, and aldrin depicted the Chenab River as a serious pollution risk zone. The outcomes of the Pearson correlation coefficient analysis represent the positive correlation among all OCPs, revealing the common origin. Distribution trends showed substantially higher (p < 0.05) contents of analyzed OCPs along the downstream zone. With regards to USEPA human health hazard assessment model, the estimated non-carcinogenic (ΣHI) and non-carcinogenic (ΣTCR) risk ranged from 1.1 × 10-5 to 1.0 × 10-1, 4.0 × 10-8 to 3.2 × 10-4 respectively. TCR >10-4 illustrated a substantial cancer health risk posed by α-HCH, heptachlor, aldrin, and dieldrin in the downstream zone. We recommend the urgent cessation of the ongoing discharge of OCPs into the Chenab River, which needs to be highlighted owing to the significant cancer risk to public health to ensure the good health and wellbeings.

High-throughput computational screening and in vitro evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl) phenyl]-1H-isoindole-1,3(2H)-dione (C3), as a novel EGFR-HER2 dual inhibitor in gastric tumors.

Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation, adhesion, angiogenesis, and metastasis. Conventional therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic mutations. Hence, dual inhibition strategies are recommended to increase potency and reduce cytotoxicity. In this study, we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase activities. Diversity-based High-throughput Virtual Screening (D-HTVS) was used to screen the whole ChemBridge small molecular library against EGFR and HER2. The atomistic molecular dynamic simulation was conducted to understand the dynamics and stability of the protein-ligand complexes. EGFR/HER2 kinase enzymes, KATOIII, and Snu-5 cells were used for in vitro validations. The atomistic Molecular Dynamics simulations followed by solvent-based Gibbs binding free energy calculation of top molecules, identified compound C3 (5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl) phenyl]-1H-isoindole-1,3(2H)-dione) to have a good affinity for both EGFR and HER2. The predicted compound, C3, was promising with better binding energy, good binding pose, and optimum interactions with the EGFR and HER2 residues. C3 inhibited EGFR and HER2 kinases with IC50 values of 37.24 and 45.83 nM, respectively. The GI50 values of C3 to inhibit KATOIII and Snu-5 cells were 84.76 and 48.26 nM, respectively. Based on these findings, we conclude that the identified compound C3 showed a conceivable dual inhibitory activity on EGFR/HER2 kinase, and therefore can be considered as a plausible lead-like molecule for treating gastric cancers with minimal side effects, though testing in higher models with pharmacokinetic approach is required.

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications.

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound's structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 µg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets.

Distribution and epidemiological features of cutaneous leishmaniasis in Asir province, Saudi Arabia, from 2011 to 2020.

BACKGROUND: Cutaneous leishmaniasis (CL) places a major burden on the health authorities in Saudi Arabia. Information about the geographical reach and seasonality of CL in Asir province remains limited. Therefore, this study aimed to investigate the epidemiological features of CL in southwest Saudi Arabia. METHODS: Retrospective data from CL patients was collected from the regional vector control unit in Asir province over 9 years. Information analysis was performed using R statistic language (version 4.0.5) and the spatial distribution of cases was mapped using QGIS (version 3.20.0). RESULTS: A total of 1565 CL cases were recorded from 2011 to 2020. Saudi male citizens were at the highest risk of CL infection. However, children under the age of 13 years were most at risk of contracting CL. CL lesions were primarily located on the face and most cases were reported in the winter and autumn seasons. Spatially, the governates of Abha, Sarat-Abidah and Khamis-Mushait had the highest CL infection prevalence. Moreover, a geographical expansion of CL from Abha to Khamis-Mushait governate was noted during past ten years. CONCLUSIONS: This is the first large scale study to investigate the seasonality, spatial distribution and demographics of CL in Asir province. It describes how the geographical change of CL incidence differs in Asir province and reveals those people most at of CL infections. This study highlights the importance of incorporating improved living conditions, school education and public awareness in the development of CL control policies.

CB-RAF600E-1 exerts efficacy in vemurafenib-resistant and non-resistant-melanoma cells via dual inhibition of RAS/RAF/MEK/ERK and PI3K/Akt signaling pathways.

Background and Aim: Predicting novel dual inhibitors to combat adverse effects such as the development of resistance to vemurafenib in melanoma treatment due to the reactivation of MAPK and PI3K/AKT signaling pathways is studied to help in reversal of cancer symptoms.Reversal of cancer symptoms in melanoma associated with vemurafenib resistance is driven by reactivation of MAPK and PI3K/Akt signaling pathways. Novel dual inhibitors targeting these proteins would be beneficial to combat resistance. Methods: High-throughput virtual screening of the ChemBridge library against B-RAFV600E and Akt was performed using an automated protocol with the AutoDock VINA program. Luminescence and time-resolved fluorescence kits were used to measure enzyme activities. The MTT assay was used to determine proliferation in normal and vemurafenib-resistant A375 cells. Flow cytometry was used to examine apoptosis, cell cycle, and phosphorylation of ERK/Akt signaling pathway. Results: High-throughput screening from the ChemBridge library identified 15 compounds with high binding energy towards B-RAFV600E; among these, CB-RAF600E-1 had the highest ΔGbinding score -11.9 kcal/mol. The compound also had a high affinity towards Akt, with a ΔGbinding score of -11.5 kcal/mol. CB-RAF600E-1 dose-dependently inhibited both B-RAFV600E and Akt with IC50 values of 635 nM and 154.3 nM, respectively. The compound effectively controlled the proliferations of normal and vemurafenib-resistant A375 cells, with GI50 values of 222.3 nM and 230.5 nM, respectively. A dose-dependent increase in the sub G0/G1 phase of the cell cycle and total apoptosis was observed following compound treatment in both normal and vemurafenib-resistant melanoma cells. Treatment with CB-RAF600E-1 decreased the pERK/pAkt dual-positive populations in normal and vemurafenib-resistant A375 cells. Conclusion: CB-RAF600E-1, identified as a novel dual inhibitor effective against normal and vemurafenib-resistant melanoma cells, requires further attention for development as an effective chemotherapeutic agent for melanoma management.

Antibacterial and anti-biofilm activity of plumbagin against multi-drug resistant clinical bacterial isolates.

OBJECTIVES: To evaluate the antibacterial activity of plumbagin (PGN) against multidrug resistance (MDR) clinical isolates. METHODS: This study was carried out at the Department of Clinical Lab Sciences, King Khalid University from October 6, 2021 to December 14, 2021. We investigated the antibacterial and anti-virulence activity of PGN against MDR Gram-negative (Escherichia coli, Klebsiella pneumoniae, Salmonella Typhi, and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus [S. aureus], Staphylococcus saprophyticus [S. saprophyticus], Streptococcus pyogenes, and Enterococcus faecalis) clinical bacterial isolates. Agar well diffusion, microdilution assay, colony count method, biofilm formation, and time-kill kinetics were employed to probe the MIC, MBC, and anti-virulence activity of PGN. RESULTS: Plumbagin inhibited the growth of all tested isolates, with S. saprophyticus exhibiting the highest sensitivity. MIC values ranged from 0.029 to 0.117 µg/mL whereas MBC ranged from 0.235 to 0.94 µg/mL, with 79% to 99% growth inhibition. Moreover, all tested isolates showed a marked decrease in biofilm formation, with S. saprophyticus and S. aureus being the most sensitive. CONCLUSION: Plumbagin is a stand-alone, broad spectrum antibacterial with promising potential against the rising threat of antimicrobial resistance.

Application of piecewise fractional differential equation to COVID-19 infection dynamics.

We proposed a new mathematical model to study the COVID-19 infection in piecewise fractional differential equations. The model was initially designed using the classical differential equations and later we extend it to the fractional case. We consider the infected cases generated at health care and formulate the model first in integer order. We extend the model into Caputo fractional differential equation and study its background mathematical results. We show that the fractional model is locally asymptotically stable when R 0 < 1 at the disease-free case. For R 0 ≤ 1 , we show the global asymptotical stability of the model. We consider the infected cases in Saudi Arabia and determine the parameters of the model. We show that for the real cases, the basic reproduction is R 0 ≈ 1 . 7372 . We further extend the Caputo model into piecewise stochastic fractional differential equations and discuss the procedure for its numerical simulation. Numerical simulations for the Caputo case and piecewise models are shown in detail.

Encapsulation of Lactic Acid Bacteria by Lyophilisation with Its Effects on Viability and Adhesion Properties.

Lactobacillus (LAB) genera are considered important functional food but are found to have a short shelf life. In this study, two LAB, Lactobacillus plantarum (Lp) and Lactobacillus rhamnosus (Lr), were isolated from sheep's milk, and whole-genome sequencing was carried out by using 16s rRNA Illumina Nextseq, the Netherlands. The LAB were encapsulated by the lyophilisation technique using different lyoprotective pharmaceutical excipients. This process was carried out using a freeze dryer (U-TECH, Star Scientific Instruments, India). Shelf-life determination was carried out by a 12-month study using the viability survival factor (Vsf). The in vitro cell adhesion technique was carried out by using the red snapper fish along with autoaggregation and cell surface hydrophobicity as vital probiotic properties. It was observed that Lp has a significantly higher (P < 0.001) Vsf of 7.2, while Lr has a Vsf of 7 (P < 0.05) when both are encapsulated with 10% maltodextrin + 5% sucrose kept at 4°C for 12 months. The result demonstrated that Lp had significantly high (P < 0.05) cell adhesion, 96% ± 1.2 autoaggregation, and 6% cell surface hydrophobicity as compared to Lr. Moreover, this study demonstrated that lyophilised LAB with lyoprotective excipients enhances shelf life without any changes in probiotic properties when kept at 4°C exhibiting all its probiotic properties.

Synergistic Role of Plant Extracts and Essential Oils against Multidrug Resistance and Gram-Negative Bacterial Strains Producing Extended-Spectrum ß-Lactamases.

Plants, being the significant and natural source of medication for humankind against several ailments with characteristic substances hidden on them, have been recognized for many centuries. Accessibility of various methodologies for the revelation of therapeutically characteristic items has opened new avenues to redefine plants as the best reservoirs of new structural types. The role of plant metabolites to hinder the development and movement of pathogenic microbes is cherished. Production of extended-spectrum ß-lactamases is an amazing tolerance mechanism that hinders the antibacterial treatment of infections caused by Gram-negative bacteria and is a serious problem for the current antimicrobial compounds. The exploration of the invention from sources of plant metabolites gives sustenance against the concern of the development of resistant pathogens. Essential oils are volatile, natural, complex compounds described by a solid odor and are framed by aromatic plants as secondary metabolites. The bioactive properties of essential oils are commonly controlled by the characteristic compounds present in them. They have been commonly utilized for bactericidal, virucidal, fungicidal, antiparasitic, insecticidal, medicinal, and antioxidant applications. Alkaloids are plant secondary metabolites that have appeared to have strong pharmacological properties. The impact of alkaloids from Callistemon citrinus and Vernonia adoensis leaves on bacterial development and efflux pump activity was assessed on Pseudomonas aeruginosa. Plant-derived chemicals may have direct antibacterial activity and/or indirect antibacterial activity as antibiotic resistance modifying agents, increasing the efficiency of antibiotics when used in combination. The thorough screening of plant-derived bioactive chemicals as resistance-modifying agents, including those that can act synergistically with antibiotics, is a viable method to overcome bacterial resistance. The synergistic assessment studies with the plant extract/essential oil and the antibiotic compounds is essential with a target for achieving a redesigned model with sustainable effects which are appreciably noticeable in specific sites of the plants compared to the entirety of their individual parts.

Nanoparticles: Synthesis and Their Role as Potential Drug Candidates for the Treatment of Parasitic Diseases.

Protozoa, helminths and ectoparasites are the major groups of parasites distributed worldwide. Currently, these parasites are treated with chemotherapeutic antiprotozoal drugs, anti-helminthic and anti-ectoparasitic agents, but, with the passage of time, resistance to these drugs has developed due to overuse. In this scenario, nanoparticles are proving to be a major breakthrough in the treatment and control of parasitic diseases. In the last decade, there has been enormous development in the field of nanomedicine for parasitic control. Gold and silver nanoparticles have shown promising results in the treatments of various types of parasitic infections. These nanoparticles are synthesized through the use of various conventional and molecular technologies and have shown great efficacy. They work in different ways, that include damaging the parasite membrane, DNA (Deoxyribonucleic acid) disruption, protein synthesis inhibition and free-radical formation. These agents are effective against intracellular parasites as well. Other nanoparticles, such as iron, nickel, zinc and platinum, have also shown good results in the treatment and control of parasitic infections. It is hoped that this research subject will become the future of modern drug development. This review summarizes the methods that are used to synthesize nanoparticles and their possible mechanisms of action against parasites.

Haematological Traits in Symptomatic and Asymptomatic COVID-19 Positive Patients for Predicting Severity and Hospitalization.

Objective: The present investigation aims on the clinical attributes and haematological parameters between symptomatic (COVID-19 ICU) and asymptomatic (COVID-19 homes isolation) patients as predisposing sign for COVID-19 related mortality. Materials and Methods: A retrospective cohort research was conducted of admitted patients to ICU, who were suffering from severe COVID-19 in Aseer Central Hospital, Abha, Kingdom of Saudi Arabia (KSA) from July 2020 until September 2020. The study included individuals with COVID -19 and ICU admission as symptomatic group and others who are COVID-19 positives with quarantine as asymptomatic group. Epidemiological, clinical and haematological laboratory data were retrospectively collected, analysed with control subjects. Results: Of the 38 ICU patients studied, the most common symptoms were fever and respiratory distress (100%), cough (86.8%). Majority were of Saudi origin (78.9%). Eighteen (47.4%) COVID-19 ICU patients showed leukocytosis, 6 (15.8%) had severe thrombocytopenia (with most having thrombocytopenia), 18 (47.4%) were anaemic. A significant correlation was observed between the WBC, RBC, Hb, platelets, neutrophil and lymphocyte count between ICU inmates compared with quarantine (p < 0.001) and RBC, Hb, neutrophil and lymphocyte count with control groups (p < 0.001). Conclusion: From the observations it is evident that, the blood tests have potential clinical value in predicting COVID-19 progression. Further, patient characteristics including age, leukocyte count, RBC, platelets and differential leukocyte counts may be significant predictors for monitoring the progression of the critical illness observed in SARS-COV-2 patients. Also, treatment procedures can be re-defined further to reduce COVID-19 mortalities in more critically ill COVID-19 individuals.

Molecular Characterization of Leishmania Species among Patients with Cutaneous Leishmaniasis in Asir Province, Saudi Arabia.

Anthroponotic cutaneous leishmaniais (ACL) and zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania tropica and Leishmania major, respectively, are endemic vector-borne diseases in southern Saudi Arabia. In 2021, an outbreak of cutaneous leishmaniasis occurred in the province of Asir. The main objective of our investigation was to analyze the epidemiological features of CL in southern Saudi Arabia. The ministry of health recorded 194 CL patients between January and December 2021 from the Asir province. Our findings showed that the majority of CL patients (87.1%) originated from the governorates of Khamis-Mushait and Abha. Most of the patients were males (62.3%). While CL affected all age groups, those under 13 years old were the most affected (38.1%). For both genders, CL patients were mostly Saudi citizens (90.7%) compared to non-Saudi expatriates. The majority of CL patients (75.2%) suffered from a single lesion, and the majority of lesions (61.3%) were located on the face. The seasonal prevalence of CL showed two peaks, a small one in July-August and a larger one in March. Of a total of 194 Giemsa slides samples, 188 showed positive amplification of Leishmania ITS1 gene. Based on PCR-RFLP and PCR-HMR, 183 patients showed positive amplification of L. tropica and five patients showed positive amplification of L. major. Phylogenetic analysis revealed a clear distinct separation between L. major and L. tropica sequences. Our results provided strong evidence of the pre-domination of L. tropica, the main etiological agent of ACL in Asir province. We reported for the first time the presence of L. major, an etiological agent of ZCL in the study areas. The co-circulation of ACL and ZCL highlighted the complexity of the epidemiology of CL in southern Saudi Arabia, and subsequently, further studies to identify competent vectors and reservoir hosts for the establishment of control strategies are needed.

Seroprevalence and Risk Factors Associated with Canine Leishmaniasis in Egypt.

BACKGROUND: Canine leishmaniasis (CanL) is caused by Leishmania infantum (L. infantum) that is transmitted by sand fly vectors with dogs acting as the main reservoir. METHODS: The present study aimed to determine the seroprevalence of CanL in dogs from Egypt and assessed the associated risk factors. The study was conducted from 2019 to 2020 in five governorates situated in Northern Egypt. Serum samples from 450 asymptomatic dogs were serologically examined by use of enzyme-linked immunosorbent assay (ELISA). RESULTS: Overall, the seroprevalence rate of CanL was 21.3% and the highest rates were observed in Cairo and Giza governorates. The univariable analysis revealed that the seropositivity of CanL was strongly related to the dogs' ages, length of hair, absence of veterinary care or application of insecticides, and the type of floor of their shelters. The risk factors that were found to be associated with CanL in exposed dogs were: age group 2-4 years old (OR = 12, 95% CI: 1.6-92.3); short hair (OR = 2.07, 95% CI: 1.2-3.6); absence of veterinary care (OR = 2.7, 95% CI: 1.3-5.8); no application of insecticides (OR = 3.09, 95% CI: 1.5-6.5) and their residence in a shelter with an earthen floor (OR = 1.42, 95% CI: 0.7-2.9). CONCLUSIONS: Based on the present results, CanL is present in Egyptian dogs and this increases the possibility of transmission by sand fly to humans with whom they have contact. Consequently, an efficient monitoring programme and effective control measures are important to reduce the risk of infection.

Prevalence of primary anti-tuberculosis drug resistance at the tertiary center in Saudi Arabia and associated risk factors.

OBJECTIVES: To estimate the prevalence mono-resistant tuberculosis (MR-TB) and multidrug resistant TB (MDR-TB), and evaluate the risk factors associated with the drug-resistant tuberculosis (DR-TB). METHODS: A descriptive, retrospective study was applied, utilizing the TB patients' medical records at King Fahd Armed Forces Hospital (KFAFH), Jeddah, Saudi Arabia. The records of patients notified between 2000 and 2018 were reviewed and culture positive cases for Mycobacterium tuberculosis species were included. Moreover, the risk factors included were age, gender, smoking history, renal disease, liver disease, hyperbilirubinemia, diabetes mellitus, and human immunodeficiency virus (HIV). RESULTS: Nine hundred and one cases in entirety were involved in the research, out of which 193 had drug-resistant tuberculosis (DR-TB) (21.4%). Out of the 21.4% DR-TB, 91.7% were MR-TB and 8.3% were MDR-TB. The highest MR prevalence was for pyrazinamide at 33.4%, while the lowest resistance was for ethambutol at 7.1%. For the risk factors of drug-resistant TB, only age depicted a statistically significant (p<0.01) but weak negative (r= -0.145) correlation with anti-TB drug resistance. CONCLUSION: Rates of DR-TB reported in the study are considered higher compared to the recently reported national and international rates. According to the results, only younger people are at risk of developing DR-TB. Moreover, genetic mutation may play a role in drug resistance among our cases specifically for pyrazinamide monoresistance.

Anticancer efficacy of 3-(4-isopropyl) benzylidene-8-ethoxy, 6-methyl, chroman-4-one (SBL-060), a novel, dual, estrogen receptor-Akt kinase inhibitor in acute myeloid leukemia cells.

Estrogen receptor (ER) α is expressed in a subset of patient-derived acute myeloid leukemia (AML) cells, whereas Akt is predominantly expressed in most types of AML. Targeting AML with dual inhibitors is a novel approach to combat the disease. Herein, we examined a novel small molecule, 3-(4-isopropyl) benzylidene-8-ethoxy,6-methyl, chroman-4-one (SBL-060), capable of targeting AML cells by inhibiting ERα and Akt kinase. The chemical properties of SBL-060 were identified by proton nuclear magnetic resonance (1H-NMR), 13C-NMR, and mass spectroscopy. In silico docking was performed using an automated protocol with AutoDock-VINA. THP-1 and HL-60 cell lines were differentiated using phorbol 12-myristate 13-acetate. ERα inhibition was assessed using ELISA. The MTT assay assessed cell viability. Flow cytometry was performed for cell cycle, apoptosis, and p-Akt analyses. Chemical analysis identified the compound as 3-(4-isopropyl) benzylidene-8-ethoxy,6-methyl, chroman-4-one, which showed high binding efficacy toward ER, with a ΔGbinding score of -7.4 kcal/mol. SBL-060 inhibited ERα, exhibiting IC50 values of 448 and 374.3 nM in THP-1 and HL-60 cells, respectively. Regarding inhibited cell proliferation, GI50 values of SBL-060 were 244.1 and 189.9 nM for THP-1 and HL-60 cells, respectively. In addition, a dose-dependent increase in sub G0/G1 phase cell cycle arrest and total apoptosis was observed after treatment with SBL-060 in both cell types. SBL-060 also dose-dependently increased the p-Akt-positive populations in both THP-1 and HL-60 cells. Our results indicate that SBL-060 has excellent efficacy against differentiated AML cell types by inhibiting ER and Akt kinase, warranting further preclinical evaluations.