Valsartan: An Angiotensin Receptor Blocker Modulates BDNF Expression and Provides Neuroprotection Against Cerebral Ischemic Reperfusion Injury.

AT1 receptor blockers (ARBs) are commonly used drugs to treat cardiovascular disease and hypertension, but research on their impact on brain disorders is unattainable. Valsartan (VAL) is a drug that specifically blocks AT1 receptor. Despite the previous evidence for VAL to provide neuroprotection in case of ischemic reperfusion injury, evaluation of their potential in mitigating mitochondrial dysfunction that causes neuronal cell death and neurobehavioral impairment remains unknown. The aim of this study was to evaluate the therapeutic effect of repurposed drug VAL against ischemic reperfusion injury-induced neuronal alternation. tMCAO surgery was performed to induce focal cerebral ischemic reperfusion injury. Following ischemic reperfusion injury, we analyzed the therapeutic efficacy of VAL by measuring the infarct volume, brain water content, mitochondrial oxidative stress, mitochondrial membrane potential, histopathological architecture, and apoptotic marker protein. Our results showed that VAL administrations (5 and 10 mg/kg b.wt.) mitigated the brain damage, enhanced neurobehavioral outcomes, and alleviated mitochondrial-mediated oxidative damage. In addition to this, our findings demonstrated that VAL administration inhibits neuronal apoptosis by restoring the mitochondrial membrane potential. A follow-up investigation demonstrated that VAL induces BDNF expression and promoted ischemic tolerance via modulating the Akt/p-Creb signaling pathway. In summary, our results suggested that VAL administration provided neuroprotection, ameliorated mitochondrial dysfunction, preserved the integrity of neurons, and lead to functional improvement after ischemic reperfusion injury.

Exploring the artificial intelligence and machine learning models in the context of drug design difficulties and future potential for the pharmaceutical sectors.

Artificial intelligence (AI), particularly deep learning as a subcategory of AI, provides opportunities to accelerate and improve the process of discovering and developing new drugs. The use of AI in drug discovery is still in its early stages, but it has the potential to revolutionize the way new drugs are discovered and developed. As AI technology continues to evolve, it is likely that AI will play an even greater role in the future of drug discovery. AI is used to identify new drug targets, design new molecules, and predict the efficacy and safety of potential drugs. The inclusion of AI in drug discovery can screen millions of compounds in a matter of hours, identifying potential drug candidates that would have taken years to find using traditional methods. AI is highly utilized in the pharmaceutical industry by optimizing processes, reducing waste, and ensuring quality control. This review covers much-needed topics, including the different types of machine-learning techniques, their applications in drug discovery, and the challenges and limitations of using machine learning in this field. The state-of-the-art of AI-assisted pharmaceutical discovery is described, covering applications in structure and ligand-based virtual screening, de novo drug creation, prediction of physicochemical and pharmacokinetic properties, drug repurposing, and related topics. Finally, many obstacles and limits of present approaches are outlined, with an eye on potential future avenues for AI-assisted drug discovery and design.

Assessment of airborne endotoxin in sandstorm dust and indoor environments using a novel passive sampling device in Al Zulfi city, Saudi Arabia - Establishing threshold exposure levels.

The impact of sandstorm dust events affects local air quality and public health. These issues are becoming of greater concern in Saudi Arabia. There is a significant lack of research on airborne endotoxin exposure and analysis in the Middle East countries and no coherent body of research exists focusing on sandstorm dust in worldwide. In this study, we used a novel design of an aluminum foil plate (AFP) electrostatic dust cloth (EDC) for the passive air sampling of sandstorm dust. A total of 38 sandstorm dust samples were collected during sandstorm episodes occurring between January and April 2020 in both indoor (7 days, n = 20) and outdoor environments (24 h, n = 18). After exposure, and following an extraction procedure, bacterial endotoxin levels were measured using the Limulus Amoebocyte Lysate (LAL) gel clot method. The study highlights that the airborne endotoxin level observed was between 10 and 200 EU/m2 in both indoor and outdoor environments, during a sandstorm event. Agricultural activities and farmhouses observed higher airborne endotoxin levels. In general, increased endotoxin levels were related to the severity of the sandstorms. Given that the observed values were high as per existing guidelines for respiratory health, we recommend the setting an occupational airborne exposure limit for bacterial endotoxin. This is the first report and further studies across various sandstorm-hit regions will need to be undertaken, together with various sampling methods, in order to assess for seasonal and geographic trends.

Understanding the structural insights of enzymatic conformations for adenylosuccinate lyase receptor in malarial parasite Plasmodium falciparum.

The dreadful disease malaria is one among the infectious diseases that comes in third number after the tuberculosis and HIV. This disease is spread by female Anopheles mosquito and caused by the malarial parasite sp notably Plasmodium falciparum. In this, the organism has several enzymes for processing the infection and growth mechanism and among that, the adenylosuccinate lyase is an enzyme that plays a critical role in metabolism and cellular replication via its action in the de novo purine biosynthetic pathway. Adenylosuccinate has been studied for two reaction mechanisms, and in that, the adenylosuccinate to AMP and fumarate is core important. As of now, there have been several studies indicating the reaction mechanism of adenylosuccinate lyase, this study projects the conformations of the reactant and product changes through molecular docking and molecular dynamic simulations. Adenylosuccinate bound complex involves His role in the product than the reactant complex, and the complex shows high flexibility due to fumarate. Thus, identifying the core inhibitor that binds to His rings could be a standard adenylosuccinate lyase inhibitor, that can block the malarial diseases in humans. In addition to the competitive inhibition site, we also predicted the uncompetitive ligand binding site, which suggest the alternate region to be targeted. Thus, from this work, we suggest both competitive and uncompetitive binding regions for the purpose identifying the malarial inhibitors.

Epidemiological trends of malaria in the Western regions of Saudi Arabia: a cross sectional study.

INTRODUCTION: Saudi Arabia has successfully reduced malaria cases to be constrained largely in the western regions. This study aimed to determine the epidemiological trends of malaria infection in five western regions of Saudi Arabia. METHODOLOGY: A retrospective analysis was conducted to investigate the epidemiological trends of malaria infection in the western regions, based on the published registry of the Saudi Ministry of Health, during the period from 2014 to 2017 using the appropriate statistical tools. RESULTS: A total of 8925 confirmed cases of malaria were reported in the western regions during the period from 2014 to 2017 with the mean of 2231 malaria cases per year. The minimum (n = 1097) and maximum (n = 4075) number of cases were reported in 2014 and 2016 respectively. The highest (n = 5919, 66.3%) number of cases were reported from Jazan region, while lowest (n = 86, 1.0%) number of cases were reported from Al-Bahah region. Plasmodium falciparum was the most frequently reported species with 7485 (83.9%) cases, while Plasmodium vivax accounted 1386 (15.5%) cases. Plasmodium malariae and mixed infections were insignificant and accounted 0.5% (n = 48) and 0.1% (n = 6) cases respectively. In relation to malaria infection and age group, malaria was predominant in > 15 age group. The highest number of malaria cases in almost all years was observed from January until March and the lowest number was reported from May until July. CONCLUSIONS: Plasmodium falciparum was the most dominant species in this survey and Jazan was the most affected region.

Morphometric and molecular characterisation of Hepatozoon bashtari n. sp. in painted saw-scaled viper, Echis coloratus (Ophidia, Viperidae).

Hepatozoon species are the most widely known haemogregarines infecting a wide range of vertebrates, although predominately snakes. Herein, Hepatozoon bashtari n. sp., originally infecting the painted saw-scaled viper, Echis coloratus, in Saudi Arabia is described using both morphological features and molecular data from 18S rDNA sequences. The overall prevalence of infection was 60% (9/15) with parasitaemia ranging from 52 to 60%. Gamonts were entirely intraerythrocytic and were observed to cause considerable hypertrophy within the host cell. The mean size of mature gamonts was 15.4 × 3.3 µm. Merogonic stages were confined to the lung endothelial cells with monomorphic meronts. The average size of mature meronts was 32 × 12 µm and they were estimated to produce 13-16 merozoites each. The phylogenetic tree generated from SSU rDNA sequences revealed that Hepatozoon bashtari sp. n. clusters with the vast majority of other Hepatozoon species infecting snakes, lizards and geckos in various regions of the world, which would appear to support the hypothesis of prey-predator transmission of the genus Hepatozoon. Through a combination of morphological comparison with closely related Hepatozoon spp. and 18S rRNA gene sequence analysis, it is possible to confirm Hepatozoon bashtari sp. n. as a new species.

In vitro Scolicidal effects of Androctonus crassicauda (Olivier, 1807) venom against the protoscolices of Echinococcus granulosus.

Hydatidosis is a zoonotic disease that commonly occurs in several places around the world, especially in the Middle East, due to infection by the larval stage of Echinococcus granulosus. This disease impacts an immense effect on the economic and public health of both humans and animals. Despite their effectiveness, the unacceptable side effects and progressive resistance to scolicidal agents may limit their use. According to their biopharmaceutical activity and benefits, numerous studies have reported that scorpion venom and its derivatives represent important resources for therapeutic applications. Therefore, this study was designed to investigate the in vitro scolicidal consequences of the crude venom of Androctonus crassicauda on E. granulosus. For this purpose, protoscolices from infected organs of camel containing hydatid cysts were collected, separated, and washed. The scolicidal impacts of three different concentrations of the crude venom (20, 50, and 100 µg/mL) were tested at different times of exposure (30, 60, 120, and 240 min). Particularly, eosin exclusion test was used to examine the viability of the protoscolices. The study results showed that the crude venom at 100 µg/mL destroys all protoscolices after 240 min incubation. Also, the scolicidal activity of venom increased significantly according to the time of exposure. In conclusion, the crude venom of A. crassicauda demonstrated high scolicidal activity in vitro against protoscolices of hydatid cysts in low concentration and short exposure time. However, the efficacy of scorpion venom remains to be evaluated in vivo for the treatment of hydatidosis in both humans and domesticated animals.

Therapeutic potential of the methanolic extract of Lepidium sativum seeds on mice infected with Trypanosoma evansi.

The present study aimed to investigate the therapeutic potential of the methanolic extract of Lepidium sativum seeds in mice experimentally infected with Trypanosoma evansi. A total of thirty-two male Swiss albino mice were randomly divided into four groups: the first group was the normal control, while the second, third and fourth groups were infected intraperitoneally with 1 × 104 trypanosomes. The third and fourth groups were treated with 100 µl of Lepidium sativum seed extract (LSSE) at a dose of 200 mg/kg body weight intraperitoneally (infected + LSSEI) and orally (infected + LSSEO) respectively, once a day, for a period of four days. Parasitaemia was found to be significantly raised in the untreated infected group, reaching 2 × 107 at day 4 post-infection, but was significantly reduced by 65.5% and 88% in the mice treated orally and intraperitoneally with LSSE, respectively. The erythrocyte count, HCT, haemoglobin content, leucocyte count and the percentage of lymphocytes was significantly reduced in the untreated infected group, while the treatment with LSSE returned these parameters to their pre-infection values. In addition, our study proved that LSSE provided protection against liver tissue damage and decreased the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The present study also established that intraperitoneal injection of LSSE is more effective than oral administration in the treatment of trypanosome infection in mice. In conclusion, the infection caused haematological, biochemical and histological changes that were ameliorated following treatment with LSSE.

Prevalence of Intestinal Parasitic Infections among Patients of King Fahd Medical City in Riyadh Region, Saudi Arabia: A 5-Year Retrospective Study.

This study is a retrospective analysis of the recorded intestinal parasitic infections for in- and outpatients visiting King Fahd Medical City, Riyadh, Saudi Arabia, from 2013 to 2017. In this study, a total of 5987 in- and outpatient were examined for intestinal parasitic infection. 30 patients out of 5987 were infected with 6 species of intestinal parasites with prevalence rate 0.5%. These parasites were Entamoeba histolytica (P = 0.27%), Cryptosporidium sp. (P = 0.1%), Giardia lamblia (P = 0.07%), Trichuris trichiura (P = 0.03%), Hymenolepis nana (P = 0.02%), and Chilomastix mesnili (P = 0.02%). The prevalence of infection in both males and females was 0.38% and 0.58%, respectively. Also, the prevalence of infection in different years and age groups as well as different seasons was provided. Intestinal parasitic infections are still a public health problem in Riyadh region, Saudi Arabia. Updating the epidemiologic survey of these parasites at regular intervals using the appropriate statistical methods is necessary to develop effective prevention and control strategies.