The effect of mephedrone on human neuroblastoma and astrocytoma cells.

Mephedrone is an illegal drug that is used recreationally. Few studies have been conducted to investigate the mechanisms by which mephedrone is harming cells. In this research, we investigated the effect of mephedrone using toxicology coupled with LC-MS/MS based metabolomics in the two CNS derived cell lines. Methods of assessment such as neutral red (NR) assay, dimethylthiazolyl diphenyltetrazolium bromide (MTT), lactose dehydrogenase (LDH) measurement, and morphology were performed to identify the effect on cell viability and to identify the best concentration to be used in a metabolomics study. A concentration of 100 µM of mephedrone was used in the metabolomic experiment because at this concentration mephedrone had induced several intracellular changes. Although there no clear indicators of cellular damage caused by mephedrone. In astrocytes there was a clear indication that cell membrane function might be impaired by depletion of ether lipids.

Therapeutic strategy of biological macromolecules based natural bioactive compounds of diabetes mellitus and future perspectives: A systematic review.

High blood glucose levels are a hallmark of the metabolic syndrome known as diabetes mellitus. More than 600 million people will have diabetes by 2045 as the global prevalence of the disease continues to rise. Contemporary antidiabetic drugs reduce hyperglycemia and its consequences. However, these drugs come with undesirable side effects, so it's encouraging that research into plant extracts and bioactive substances with antidiabetic characteristics is on the rise. Natural remedies are preferable to conventional anti-diabetic drugs since they are safer for the body, more affordable and have fewer potential adverse effects. Biological macromolecules such as liposomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles, nanoemulsions and metallic nanoparticles are explored in this review. Current drug restrictions have been addressed, and the effectiveness of plant-based antidiabetic therapies has enhanced the merits of these methods. Plant extracts' loading capacity and the carriers' stability are the primary obstacles in developing plant-based nanocarriers. Hydrophilic, hydrophobic, and amphiphilic drugs are covered, and a brief overview of the amphipathic features of liposomes, phospholipids, and lipid nanocarriers is provided. Metallic nanoparticles' benefits and attendant risks are highlighted to emphasize their efficiency in treating hyperglycemia. Researchers interested in the potential of nanoparticles loaded with plant extracts as antidiabetic therapeutics may find the current helpful review.

Synthesis and Characterization of Graphene Oxide/Polyethylene Glycol/Folic Acid/Brucine Nanocomposites and Their Anticancer Activity on HepG2 Cells.

Background: Liver cancer is the sixth most prevalent form of cancer and the second major cause of cancer-associated mortalities worldwide. Cancer nanotechnology has the ability to fundamentally alter cancer treatment, diagnosis, and detection. Objective: In this study, we explained the development of graphene oxide/polyethylene glycol/folic acid/brucine nanocomposites (GO/PEG/Bru-FA NCs) and evaluated their antimicrobial and anticancer effect on the liver cancer HepG2 cells. Methodology: The GO/PEG/Bru-FA NCs were prepared using the co-precipitation technique and characterized using various techniques. The cytotoxicity of the GO/PEG/Bru-FA NCs was tested against both liver cancer HepG2 and non-malignant Vero cells using an MTT assay. The antimicrobial activity of the GO/PEG/Bru-FA NCs was tested against several pathogens using the well diffusion technique. The effects of GO/PEG/Bru-FA NCs on endogenous ROS accumulation, apoptosis, and MMP levels were examined using corresponding fluorescent staining assays, respectively. The apoptotic protein expressions, such as Bax, Bcl-2, and caspases, were studied using the corresponding kits. Results: The findings of various characterization assays revealed the development of GO/PEG/Bru-FA NCs with face-centered spherical morphology and an agglomerated appearance with an average size of 197.40 nm. The GO/PEG/Bru-FA NCs treatment remarkably inhibited the growth of the tested pathogens. The findings of the MTT assay evidenced that the GO/PEG/Bru-FA NCs effectively reduced the HepG2 cell growth while not showing toxicity to the Vero cells. The findings of the fluorescent assay proved that the GO/PEG/Bru-FA NCs increased ROS generation, reduced MMP levels, and promoted apoptosis in the HepG2 cells. The levels of Bax, caspase-9, and -3 were increased, and Bcl-2 was reduced in the GO/PEG/Bru-FA NCs-treated HepG2 cells. Conclusion: The results of this work demonstrate that GO/PEG/Bru-FA NCs suppress viability and induce apoptosis in HepG2 cells, indicating their potential as an anticancer candidate.

Beyond traditional medications: exploring novel and potential inhibitors of trypanothione reductase (LmTr) of Leishmania parasites.

The trypanothione reductase enzyme, which neutralizes the reactive oxygen species produced inside the macrophages to kill the parasites, is one of the evasion strategies Leishmania uses to survive inside the cells. The vitality of the parasite depends on Leishmania major trypanothione reductase (LmTr), a NADPH-dependent flavoprotein oxidoreductase essential for thiol metabolism. Since this enzyme is distinct and lacking in humans, we focused on it in our study to screen for new inhibitors to combat leishmaniasis. Using the I-TASSER server, a three-dimensional model of LmTr was generated. The Autodock vina program was used in high-throughput virtual screening of the ZINC database. The top seven molecules were ranked according to their binding affinity. The compounds with the highest binding affinities and the right number of hydrogen bonds were chosen. These compounds may be effective at inhibiting the target enzyme's (LmTr) activity, making them new leishmaniasis treatments. These compounds may serve as a useful starting point for a hit-to-lead approach in the quest for new anti-Leishmania drugs that are more efficient and less cytotoxic. The average node degree is 5.09, the average local clustering coefficient is 0.868, and the PPI enrichment p-value is 8.9e-06, indicating that it is sufficiently connected to regulate the network. TRYR (LmTr protein) also interacts physically with ten additional proteins in the pathogenesis network. The findings of the study indicated that successfully suppressing the LmTr protein in vitro and in vivo may finally result in regulating the L. major pathogenesis.Communicated by Ramaswamy H. Sarma.

Anise (Pimpinella anisum L.) attenuates azoxymethane-induced colorectal cancer by antioxidant, anti-inflammatory, and anti-apoptotic pathways in rats.

Herbal medicine is one of the most common fields explored for combating colon cancers, and Pimpinella anisum L. seeds (PAS) have been utilized widely as medicinal agents because of their increased essential oil (trans-anethole) contents. In this essence, our study investigates the toxic effect and chemoprotective potentials of PAS against azoxymethane (AOM)-induced colon cancer in rats. The toxicity trial for PAS conducted by clustering fifteen rats into three groups (five rats each): A, normal control had 10% Tween 20; B, ingested with 2 g/kg PAS; and C, supplemented with 4 g/kg PAS. The in vivo cancer trial was performed by using 30 rats (Sprague-Dawley) that were randomly adapted in five steel cages (six rats each): group A, normal controls received two subcutaneous injections of normal saline 0.09% and ingested orally 10% Tween 20; groups B-E, rats received two injections of 15 mg/kg of azoxymethane (AOM) subcutaneously in 2 weeks and treated orally with 10% Tween 20 (group B) or intraperitoneal injection of 5-fluorouracil (35 mg/kg) (group C), or orally given 200 mg/kg PAS (group D) and 400 mg/kg PAS (group E) for 8 weeks. After the scarification of rats, the colon tissues were dissected for gross and histopathological evaluations. The acute toxicity trial showed the absence of any toxic signs in rats even after 14 days of ingesting 4 g/kg of PAS. The chemoprotective experiment revealed significant inhibitory potentials (65.93%) of PAS (400 mg/kg) against aberrant crypto foci incidence that could be correlated with its positive modulation of the immunohistochemically proteins represented by a significant up-regulation of the Bax protein and a decrease of the Bcl-2 protein expressions in colon tissues. Furthermore, PAS-treated rats had notably lower oxidative stress in colon tissues evidenced by decreased MDA levels and increased antiradical defense enzymes (SOD, CAT, and GPx). The outcomes suggest 400 mg/kg PAS as a viable additive for the development of potential pharmaceuticals against colorectal cancer.

Chitosan biopolymer functionalized with graphene oxide and titanium dioxide with Escin metallic nanocomposites for anticancer potential against colon cancer.

Our study produced GO-TiO2-chitosan-escin nanocomposites (GTCEnc), characterized them using physical and biological methods, and evaluated their potential as cancer treatment candidates. Standard protocols were used to produce GTCEnc. Nanocomposites are created using XRD, FTIR, UV-Vis, and PL spectroscopy analysis. The morphology and ultrastructure of nanocomposites were investigated using SEM and TEM. Nanocomposites containing TiO2, GO, chitosan, and escin nanostructures were characterized using diffraction, microscopy, and spectroscopy; the antimicrobial activity of GTCEnc was investigated. Various methods were used to test the anticancer activity of GTCEnc against COLO 205 cell lines, including MTT, EtBr/AO, DAPI, JC-1, Annexin-V/FITC, cell cycle analysis, and activation of pro-apoptotic markers, such as caspase-3, -8, and -9. The nanocomposites were cytotoxic to COLO 205 cells, with an IC50 of 22.68 µg/mL, but not to 293T cells. In cells treated with nanomaterials, cytotoxicity, nuclear damage, apoptosis induction, and free radical production were significantly increased. Our finding suggests that GTCEnc has potent anticancer and antibacterial activity in vitro because of its unique nanocomposite properties and antibacterial and anticancer activity in vitro. Additional research is required to understand the clinical efficacy of these nanocomposites.

Computer-aided identification of dengue virus NS2B/NS3 protease inhibitors: an integrated molecular modelling approach for screening of phytochemicals.

Globally, dengue (DENV) fever has appeared as the most widespread vector-borne disease, affecting more than 100 million individuals annually. No approved anti-DENV therapy or preventive vaccine is available yet. DENV NS3 protein is associated with protease activity and is essential for viral replication process within the host cell. NS2B is linked with NS3 protein as a cofactor. Hence, NS3/NS2B is a potential druggable target for developing inhibitors against dengue virus. In the present study, a dataset of Beta vulgaris L.-based natural compounds was developed. Virtual ligand screening of 30 phytochemicals was carried out to find novel inhibitors against the NS2B/NS3 protein. Spatial affinity, drug-likeness, and binding behaviors of selected phytochemicals were analyzed. Post-simulation analysis, including Principal Component Analysis (PCA), MMGBSA, and Co-relation analysis, was also performed to provide deep insight for elucidating protein-ligand complexes. This computer-aided screening scrutinized four potent phytochemicals, including betavulgaroside II, vitexin xyloside, epicatechin, and isovitexin2-O-xyloside inhibitors exhibiting optimal binding with viral NS3/NS2B protein. Our study brings novel scaffolds against DENV NS2B/NS3 of serotype-2 to act as lead molecules for further biological optimization. In future, this study will prompt the exploration and development of adjuvant anti-DENV therapy based on natural compounds.Communicated by Ramaswamy H. Sarma.

An application of carbohydrate polymers-based surface-modified gold nanoparticles for improved target delivery to liver cancer therapy - A systemic review.

Gold nanoparticles have been broadly investigated as cancer diagnostic and therapeutic agents. Gold nanoparticles are a favorable drug delivery vehicle with their unique subcellular size and good biocompatibility. Chitosan, agarose, fucoidan, porphyran, carrageenan, ulvan and alginate are all examples of biologically active macromolecules. Since they are biocompatible, biodegradable, and irritant-free, they find extensive application in biomedical and macromolecules. The versatility of these compounds is enhanced because they are amenable to modification by functional groups like sulfation, acetylation, and carboxylation. In an eco-friendly preparation process, the biocompatibility and targeting of GNPs can be improved by functionalizing them with polysaccharides. This article provides an update on using carbohydrate-based GNPs in liver cancer treatment, imaging, and drug administration. Selective surface modification of several carbohydrate types and further biological uses of GNPs are focused on.

Carbohydrate polymers-based surface modified nano delivery systems for enhanced target delivery to colon cancer - A review.

Carbohydrate polymers-based surface-modified nano-delivery systems have gained significant attention in recent years for enhancing targeted delivery to colon cancer. These systems leverage carbohydrate polymers' unique properties, such as biocompatibility, biodegradability, and controlled release. These properties make them suitable candidates for drug delivery applications. Nano-delivery systems loaded with bioactive compounds are well-studied for targeted colorectal cancer delivery. However, those drugs' target reach is still limited in various nano-delivery systems. To overcome this limitation, surface modification of nanoparticles with carbohydrate polymers like chitosan, pectin, alginate, and guar gum showed enhanced target-reaching capacity along with enhanced anticancer efficacy. Recently, a chitosan-decorated PLGA nanoparticle was constructed with tannic acid and vitamin E and showed long-term release of specific targets along with higher anticancer efficacy. Similarly, Chitosan-conjugated glucuronic acid-coated silica nanoparticles loaded with capecitabine were studied against colon cancer and found to be the pH-responsive controlled release of capecitabine with higher anticancer efficacy. Surface-modified carbohydrate polymers have promising potential for improving colon cancer target delivery. By leveraging the unique properties of these polymers, such as surface modification, pH responsiveness, mucoadhesion, controlled drug release, and combination therapy, researchers are working toward developing more effective and targeted treatment strategies for colon cancer.

Case Reports Study on Methanol Poisoning in King Abdul Aziz Specialist Hospital, Taif, Saudi Arabia.

Methanol poisoning is a challenging issue due to its inducing acute multiple organ failures, and especially due to a lack of preparedness, available antidotes, and management protocols. The current study presents six cases of methanol poisoning that attended the emergency department of King Abdul Aziz Specialist Hospital, Taif, Saudi Arabia, between March and November 2022. All of the patients suffered from severe metabolic acidosis and visual impairment following the ingestion of homemade alcoholic beverages and colonia. Three patients were comatose, suffered from post-cardiac pulmonary arrest, and, finally, died, while the other three were non-comatose and discharged from the ICU after improvement. Management was based on clinical symptoms and other laboratory findings due to a shortage of methanol level measurement resources. The antidote, fomepizole, was not given to all of the cases due to its deficiency, and ethanol was given only to one patient due to difficulties in administering it without monitoring its concentration. Methanol poisoning and its outbreak provide insights into the dangers of hazardous homemade alcohol and other pharmaceutical preparations that might be adulterated with methanol, particularly to the shortage of suitable diagnostic testing and antidotes in addition to poor resources for management of intoxicated patients in some regions of Saudi Arabia.

COVID-19 and severity of liver diseases: Possible crosstalk and clinical implications.

COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.

Patterns of acute poisoning for children during outbreak of Corona virus in Makkah region Saudi Arabia.

Background: Poisoning occurs when a person is exposed to an external substance at a too high dose for them. It is possible for young children to be exposed to chemicals. Lungs, the heart, CNS, the digestive tract, and kidneys can be poisoned. In 2004, over 45,000 children and teenagers died from acute poisoning, representing 13% of all accidental poisoning deaths worldwide. Poisoning patterns vary by exposure type, age group, poison type, and dose. Aim: This study assessed the pattern of acute poisoning with drugs, chemicals, and natural toxins among children (<12 years old). The study was done in Makkah region and registered in the poison control center in Makkah, the forensic chemistry center in Haddah during 2020-2021. Methods: A retrospective cohort study was done on 122 children exposed to toxic substances in Makkah. The children were 12 years old and had good health for a maximum of one year. Stratified random sampling was used to divide cases into groups of similar poisons (pharmaceutical products, household products, plant envenomation, and animal envenomation). Then each group got a random samples. The data were analysed with SPSS software. Results: The mean age of children was 5.2 years, with 59% being boys. The mean temperature, pulse, systolic, diastolic, and respiratory rates were 36.77, 98.29, 109.1, 69.17, and 21.49. The most documented pharmaceutical products (200 mg) were carbamazepine (5 mg), methanol, risperidone (5 mg), propranolol (5 mg), and olanzapine (5 mg). The most common poison forms were tablets (42.6%), syrups (15.6%), capsules (13.9%), and solutions (13.1%). The most common poisoning routes were ingestion (82.8%), dermal (5.7%), injection (4.9%), and inhalation (6.6%). Accidental poisoning was 83%, with a 30-minute lag for 30.3% of children, and most (69.7%) occurred at home. Benzodiazepines were the most commonly used category class drug (18%), with normal pupils and an ECG of 85.2%. Sixty-seven percent had blood tests. Sickness was 9.48, and the positive result was 213.01. The most common presenting symptoms were GIT and neurological (23.8%). 31.1% had mild, moderate, or severe toxicity. Most cases (68%) were complex. 34.4% were intubated, 9.8% had repeated-dose-activated charcoal for enhanced elimination, and 27.8% were on IV fluids. Children with GIT, CVS, respiratory, dermal, and neurological symptoms had a higher percentage of severe toxicity (p < 0.05). Slight toxicity was associated with whole bowel irrigation, intubation for oxygen therapy, N-acetylcysteine or sedation, fluids, and phenytoin (P < 0.05). Complicated cases had a higher mean AST/IUL than non-complicated cases (75.5 vs. 20.08, p < 0.05). The level of toxicity did not correlate with the mean of all lab tests (p > 0.05). The age of the children correlated positively with their systolic BP (r = 0.22, p < 0.01). Conclusion: The results show how important it is to teach the public about poisoning and make rules for tracking and dealing with poisonings in Saudi Arabia.

SARS-CoV-2 Detection and COVID-19 Diagnosis: A Bird's Eye View.

The battle against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) associated coronavirus disease 2019 (COVID-19) is continued worldwide by administering firsttime emergency authorized novel mRNA-based and conventional vector-antigen-based anti- COVID-19 vaccines to prevent further transmission of the virus as well as to reduce the severe respiratory complications of the infection in infected individuals. However; the emergence of numerous SARS-CoV-2 variants is of concern, and the identification of certain breakthrough and reinfection cases in vaccinated individuals as well as new cases soaring in some low-to-middle income countries (LMICs) and even in some resource-replete nations have raised concerns that only vaccine jabs would not be sufficient to control and vanquishing the pandemic. Lack of screening for asymptomatic COVID-19-infected subjects and inefficient management of diagnosed COVID-19 infections also pose some concerns and the need to fill the gaps among policies and strategies to reduce the pandemic in hospitals, healthcare services, and the general community. For this purpose, the development and deployment of rapid screening and diagnostic procedures are prerequisites in premises with high infection rates as well as to screen mass unaffected COVID-19 populations. Novel methods of variant identification and genome surveillance studies would be an asset to minimize virus transmission and infection severity. The proposition of this pragmatic review explores current paradigms for the screening of SARS-CoV-2 variants, identification, and diagnosis of COVID-19 infection, and insights into the late-stage development of new methods to better understand virus super spread variants and genome surveillance studies to predict pandemic trajectories.

Canagliflozin alleviates valproic acid-induced autism in rat pups: Role of PTEN/PDK/PPAR-γ signaling pathways.

Autism is complex and multifactorial, and is one of the fastest growing neurodevelopmental disorders. Canagliflozin (Cana) is an antidiabetic drug that exhibits neuroprotective properties in various neurodegenerative syndromes. This study investigated the possible protective effect of Cana against the valproic acid (VPA)-induced model of autism. VPA was injected subcutaneously (SC) into rat pups at a dose of 300 mg/kg, twice daily on postnatal day-2 (PD-2) and PD-3, and once on PD-4 to induce an autism-like syndrome. Graded doses of Cana were administered (5 mg/kg, 7.5 mg/kg, and 10 mg/kg, P.O.) starting from the first day of VPA injections and continued for 21 days. At the end of the experiment, behavioral tests and histopathological alterations were assessed. In addition, the gene expression of peroxisome proliferator-activated receptor γ (PPAR γ), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase (PDK), cellular myeloctomatosis (c-Myc) with protein expression of glucose transporter-1 (GLUT-1), phosphatase and tensin homolog (PTEN), and level of acetylcholine (ACh) were determined. Treatment with Cana significantly counteracted histopathological changes in the cerebellum tissues of the brain induced by VPA. Cana (5 mg/kg, 7.5 mg/kg, and 10 mg/kg) improved sociability and social preference, enhanced stereotypic behaviors, and decreased hyperlocomotion activity, in addition to its significant effect on the canonical Wnt/ß-catenin pathway via the downregulation of gene expression of LDHA (22%, 64%, and 73% in cerebellum tissues with 51%, 60%, and 75% in cerebrum tissues), PDK (27%, 50%, and 67% in cerebellum tissues with 34%, 66%, and 77% in cerebrum tissues), c-Myc (35%, 44%, and 72% in cerebellum tissues with 19%, 58%, and 79% in cerebrum tissues), protein expression of GLUT-1 (32%, 48%, and 49% in cerebellum tissues with 30%, 50%, and 54% in cerebrum tissues), and elevating gene expression of PPAR-γ (2, 3, and 4 folds in cerebellum tissues with 1.5, 3, and 9 folds in cerebrum tissues), protein expression of PTEN (2, 5, and 6 folds in cerebellum tissues with 6, 6, and 10 folds in cerebrum tissues), and increasing the ACh levels (4, 5, and 7 folds) in brain tissues. The current study confirmed the ameliorating effect of Cana against neurochemical and behavioral alterations in the VPA-induced model of autism in rats.

Coumarin-Based Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Pre-ADME Analysis, Toxicity Profile, Computational Analysis, and In Vitro Enzyme Assay.

Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 µM in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 µM IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.

Chemopreventive Effects of Onosma mutabilis against Azoxymethane-Induced Colon Cancer in Rats via Amendment of Bax/Bcl-2 and NF-κB Signaling Pathways.

Onosma species (Boraginaceae) are well known as medicinal plants due to their wide range of pharmaceutical potential. The present study aims to investigate the anticancer (in vitro) and chemo-protective (in vivo) efficacies of Onosma mutabilis extract (OME) in the azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. The in vitro antiproliferative effects of OME were determined on two human tumor cell lines (Caco-2 and HT-29) via MTT assay. The in vivo chemoprotective effects of OME were investigated by performing various biochemical analyses in serum and tissue homogenates of albino rats, along with determining oxidative stress biomarkers. Inflammatory biomarkers of colon, colonic gross morphology (by methylene blue), ACF formation, and colonic histopathology (H & E stain) were determined. The immunohistochemistry of colonic tissues was also assessed by Bax and Bcl-2 protein expression. The results showed that the antitumor activity of OME against Caco-2 and HT-29 colorectal cancer cells ranged between 22.28-36.55 µg/mL. OME supplementation caused a significant drop in the ACF values and improved the immunohistochemistry of the rats shown by up-regulation of Bax and down-regulation of Bcl-2 protein expressions. These outcomes reveal that O. mutabilis may have chemoprotective efficiency against AOM-induced colon cancer represented by the attenuation of ACF formation possibly through inhibition of free radicals, inflammation, and stimulation of the colon antioxidant armory (SOD, CAT, and GPx) and positive regulation of the Nrf2-Keap1 pathway.

Liver Injury in Favipiravir-Treated COVID-19 Patients: Retrospective Single-Center Cohort Study.

(1) Background: Favipiravir (FVP) is a new antiviral drug used to treat COVID-19. It has been authorized to be used in the kingdom of Saudi Arabia in the treatment of COVID-19. The mechanism of action of FVP is working as a specific inhibitor for the RNA-dependent RNA polymerase of the RNA chain virus. FVP has the potential to be hepatotoxic because of the structure similarity with pyrazinamide. This retrospective study aimed to determine the prevalence of liver injury in FVP-treated COVID-19 patients in General East Jeddah Hospital, Saudi Arabia, during the COVID-19 pandemic. (2) Methods: A total of 6000 patients infected with COVID-19 and treated at the East Jeddah Hospital were included, with a sample size of 362 patients. The participants ranged from 18 to 70 years of age, both males and females, with normal hepatic and renal function and had a confirmed diagnosis of COVID-19 infection. Patients who had gouty arthritis, hepatic and renal dysfunction, dead patients, pregnant women, and breastfeeding mothers were all excluded from this study. A retrospective cohort study compared two groups of patients treated with and without FVP and who followed the Saudi Ministry of Health protocol to manage COVID-19 infection. (3) Results: An adverse effect of FVP on the liver was found that ranged from mild to severe. Stopping treatment with FVP was associated with an observed important increase in the levels of liver enzymes AST (p < 0.001), ALT (p < 0.001), alkaline phosphatase (p < 0.03), total bilirubin (p < 0.001), and direct bilirubin (p < 0.001) in the treated compared with the untreated group. (4) Conclusion: This study showed a significant difference between the treated and the untreated groups with FVP in liver injury. FVP influences the liver, increasing the blood levels of the liver function parameters.

The use of the nutritional supplements during the covid-19 outbreak in Saudi Arabia: A cross-sectional study.

BACKGROUND: COVID-19 causes moderate to severe illness and is spreading globally. During a pandemic, vitamins and minerals are vital to health. Therefore, the prevalence and epidemiology of supplement use in Saudi Arabia during the COVID-19 pandemic must be known. METHODS: This cross-sectional study was conducted in Saudi Arabia using an online survey. The study was conducted from June to March 2022 on both adults and children. The link to the survey was shared on social media platforms. The survey included questions on participants' demographics, vaccination status, supplements they used, and side effects of supplements. Participation in this study was optional, and there was no obligation to participate. There was a declaration about the aim of the study and different objectives before starting the survey. RESULTS: The present study reported that most of the participants reported that they used vitamin C (64.6 %), zinc (51.9 %), multivitamins (46.1 %), black seeds (26.7 %), garlic (Allium sativum) (15.4 %), omega-3 (22.1 %), vitamin D (22.2 %), echinacea (10.1 %), manuka honey (26.0 %), curcumin (13.6 %), ginger (22.5 %), royal jelly (12.9 %), and propolis (7.5 %) before and during the COVID-19 pandemic period. These supplements were used more frequently by subjects during the pandemic than before. DISCUSSION AND CONCLUSION: The respondents' risk of these supplements' use may partially reflect the public's behavioral response during a pandemic. Future studies can document the health beliefs and motivations of nutritional supplement users.

Potential Antioxidant Activity of Apigenin in the Obviating Stress-Mediated Depressive Symptoms of Experimental Mice.

This study aimed to examine the antidepressant properties of apigenin in an experimental mouse model of chronic mild stress (CMS). Three weeks following CMS, albino mice of either sex were tested for their antidepressant effects using the tail suspension test (TST) and the sucrose preference test. The percentage preference for sucrose solution and the amount of time spent immobile in the TST were calculated. The brain malondialdehyde (MDA) levels, catalase activity, and reduced glutathione levels were checked to determine the antioxidant potential of treatments. When compared to the control, animals treated with apigenin during the CMS periods showed significantly shorter TST immobility times. Apigenin administration raised the percentage preference for sucrose solution in a dose-dependent manner, which put it on par with the widely used antidepressant imipramine. Animals treated with apigenin displayed a significantly (p ˂ 0.05) greater spontaneous locomotor count (281) when compared to the vehicle-treated group (245). Apigenin was also highly effective in significantly (p ˂ 0.01) lowering plasma corticosterone levels (17 vs. 28 µg/mL) and nitrite (19 vs. 33 µg/mL) produced by CMS in comparison to the control group. During CMS, a high dose (50 mg/kg) of apigenin was given, which greatly increased the reduced glutathione level while significantly decreasing the brain's MDA and catalase activity when compared to the control group. As a result, we infer that high doses of apigenin may have potential antidepressant effects in animal models via various mechanisms.

Reported Cases of Alcohol Consumption and Poisoning for the Years 2015 to 2022 in Hail, Saudi Arabia.

This study aimed to determine the pattern of alcohol consumption and its poisoning among the Saudi population in the city of Hail, KSA. Data from a retrospective cohort were collected qualitatively at King Khalid Hospital (KKH) and Hail General Hospital (HGH), covering 550 participants from 2015 to 2022. Two groups were formed comprising patients admitted to the emergency room (ER) and community members; their ages ranged from 19 to 75 years. Group 1 contained 400 participants, of which 250 were patients (244 males, six females) who came to the (ER) with a suspected alcohol overdose or poisoning, and 150 were patients (128 males and 22 females) who were discharged from the (ER) with minimal complaints because of their drinking. Group 2 comprised 150 participants (128 males, 22 females) who were community members, who were surveyed using a questionnaire or interview. In Group 1, 30% of patients reported an altered state of consciousness as a major complaint, 28.8% of patients exhibited abnormal liver function tests (LFTs), 27% had abnormal renal function tests (RFT) with decreased glomerular filtration rates (GFR) and elevated levels of urea and creatinine or low levels of electrolytes or calcium, and 35.6% patients showed elevated levels of pancreatic enzymes. One death was reported due to high alcohol consumption. In Group 2, the community participants reported that they started drinking alcohol due to the influence of other people (29%), stress (11%), depression (10.8%), curiosity (4.4%), and boredom (4%). In addition, 77% of participants were frequent alcohol drinkers and 20% consumed it daily. Further, 68.7% claimed to drink alcohol for more than one hour at a time, while 83.3% experienced blackouts and 70% had problems related to their liver. Moreover, 72.7% of the participants ended up in the hospital and 34.6% suffered from multiple chronic diseases. It is concluded that social influences and stress contributed to the initiation of alcohol use. Despite data gaps, the findings of this study provide a practical understanding of alcohol consumption among the Saudi population and guidance for policymakers.