New spiro-indeno[1,2-b]quinoxalines clubbed with benzimidazole scaffold as CDK2 inhibitors for halting non-small cell lung cancer; stereoselective synthesis, molecular dynamics and structural insights.

Despite the crucial role of CDK2 in tumorigenesis, few inhibitors reached clinical trials for managing lung cancer, the leading cause of cancer death. Herein, we report combinatorial stereoselective synthesis of rationally designed spiroindeno[1,2-b]quinoxaline-based CDK2 inhibitors for NSCLC therapy. The design relied on merging pharmacophoric motifs and biomimetic scaffold hopping into this privileged skeleton via cost-effective one-pot multicomponent [3 + 2] cycloaddition reaction. Absolute configuration was assigned by single crystal x-ray diffraction analysis and reaction mechanism was studied by Molecular Electron Density Theory. Initial MTT screening of the series against A549 cells and normal lung fibroblasts Wi-38 elected 6b as the study hit regarding potency (IC50 = 54 nM) and safety (SI = 6.64). In vitro CDK2 inhibition assay revealed that 6b (IC50 = 177 nM) was comparable to roscovitine (IC50 = 141 nM). Docking and molecular dynamic simulations suggested that 6b was stabilised into CDK2 cavity by hydrophobic interactions with key aminoacids.

Hepatoprotective and Antioxidant Effects of Nanopiperine against Cypermethrin via Mitigation of Oxidative Stress, Inflammations and Gene Expression Using qRT-PCR.

Cypermethrin (Cyp) is a pyrethroid that has been associated with the toxicity of various organs. The aim of our study was to evaluate the hepatoprotective and antioxidant activities of nano-piperine (NP) against Cyp toxicity. Cyp (50 mg/kg) was administered orally in all animals of groups III-VI for 15 days. Groups IV-VI each received three doses of NP (125, 250, and 500 µg/kg/day) for 10 days after receiving the Cyp dosage, which was given after 1 h. A rise in serum biomarkers (ALT, AST, ALP, total protein, and albumin), which are indicators of toxicity alongside anomalous oxidative stress indices (lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD) and catalase), was detected. After Cyp treatment, we observed upregulated cytokines, caspase expression, and histological analysis that the showed distortion of cell shape. However, the administration of NP dramatically reversed all of the Cyp-induced alterations, inducing reductions in serum marker levels, stress level, the production of cytokines, and caspase expression. Additionally, all of the histopathological alterations were minimized to values that were comparable to normal levels. The present findings suggested that NP exhibits potent antioxidant and anti-inflammatory activities that can protect rats' livers against Cyp-induced liver damage through hepatoprotective activities.

Amphetamine-Related Fatalities and Altered Brain Chemicals: A Preliminary Investigation Using the Comparative Toxicogenomic Database.

Amphetamine is a psychostimulant drug with a high risk of toxicity and death when misused. Abuse of amphetamines is associated with an altered organic profile, which includes omega fatty acids. Low omega fatty acid levels are linked to mental disorders. Using the Comparative Toxicogenomic Database (CTD), we investigated the chemical profile of the brain in amphetamine-related fatalities and the possibility of neurotoxicity. We classified amphetamine cases as low (0-0.5 g/mL), medium (>0.5 to 1.5 g/mL), and high (>1.5 g/mL), based on amphetamine levels in brain samples. All three groups shared 1-octadecene, 1-tridecene, 2,4-di-tert-butylphenol, arachidonic acid (AA), docosahexaenoic acid (DHA), eicosane, and oleylamide. We identified chemical-disease associations using the CTD tools and predicted an association between DHA, AA and curated conditions like autistic disorder, disorders related to cocaine, Alzheimer's disease, and cognitive dysfunction. An amphetamine challenge may cause neurotoxicity in the human brain due to a decrease in omega-3 fatty acids and an increase in oxidative products. Therefore, in cases of amphetamine toxicity, a supplement therapy may be needed to prevent omega-3 fatty acid deficiency.

Synthesis and Characterization of New Spirooxindoles Including Triazole and Benzimidazole Pharmacophores via [3+2] Cycloaddition Reaction: An MEDT Study of the Mechanism and Selectivity.

A new series of spirooxindoles based on benzimidazole, triazole, and isatin moieties were synthesized via a [3+2] cycloaddition reaction protocol in one step. The single X-ray crystal structure of the intermediate triazole-benzimidazole 4 was solved. The new chemical structures of these spirooxindole molecules have been achieved for the first time. The final synthesized chemical architecture has differently characterized electronic effects. An MEDT study of the key 32CA reaction between in situ generated azomethine ylide (AY) and chalcones explained the low reaction rates and the total selectivities observed. The supernucleophilic character of AY and the strong electrophilicity of chalcones favor these reactions through a highly polar two-stage one-step mechanism in which bond formation at the ß-conjugated carbon of the chalcones is more advanced. The present combined experimental and theoretical study reports the synthesis of new spirooxindoles with potential biological activities and fully characterizes the molecular mechanisms for their formation through the key 32CA reaction step.

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats.

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.

Nephroprotective Effect of Diosmin against Cisplatin-Induced Kidney Damage by Modulating IL-1ß, IL-6, TNFα and Renal Oxidative Damage.

Cisplatin (CP) is a platinum compound of the alkylating agent class that is used for the treatment of various types of cancer. However, CP treatments in cancer patients are accountable for nephrotoxicity, as it is a major adverse effect. Hence, this research study was proposed to investigate the nephroprotective effect of diosmin, a flavonoid glycoside of hesperidin derivatives against cisplatin-induced kidney damage. Wistar rats received a single intraperitoneal (i.p) injection of CP (7.5 mg/kg, i.p) to induce nephrotoxicity. The administration of CP significantly (p < 0.001) increased the markers of kidney function test (creatinine, blood urea nitrogen, and uric acid) and demonstrated histopathological changes in the kidney of the CP-treated nephrotoxic group. In addition, the CP-treated nephrotoxic group demonstrated a significant (p < 0.001) increase in lipid peroxidation (LPO) levels and depleted activities of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT).However, diosmin (100 and 200 mg/kg) treatments significantly reduced the elevated levels of kidney function test parameters and restored structural changes in the kidney (p < 0.001). The administration of diosmin (100 and 200 mg/kg) significantly (p < 0.001) reduced LPO levels, increased GSH content and showed improvements in the activities of GPx, GR, SOD and CAT. The markers of inflammatory cytokines such as IL-1ß, IL-6 and TNFα significantly (p < 0.001) increased in the CP-treated nephrotoxic group, whereas diosmin (100 and 200 mg/kg) treatments significantly (p < 0.001) reduced the elevated levels of these cytokines. The findings of this research demonstrate the nephroprotective effect of diosmin against CP-induced kidney damage. Therefore, we conclude that diosmin may be used as a supplement in the management of nephrotoxicity associated with CP treatments in cancer patients.

Design, physicochemical characterisation, and in vitro cytotoxicity of cisplatin-loaded PEGylated chitosan injectable nano / sub-micron crystals.

The study aimed to develop cisplatin-loaded PEGylated chitosan nanoparticles. The optimal batch of cisplatin-loaded PEGylated chitosan nanoparticles had a + 49.9 mV zeta potential, PDI of 0.347, and % PDI of 58.9. Nanoparticle zeta size was 741.4 z. d.nm, the size in diameter was 866.7 ± 470.5 nm, and nanoparticle conductivity in colloidal solution was 0.739 mS/cm. Differential scanning calorimetry (DSC) revealed that cisplatin-loaded PEGylated chitosan nanoparticles had sharp endothermic peaks at temperatures at 168.6 °C. The thermogravimetric analysis (TGA) showed the weight loss of cisplatin-loaded PEGylated chitosan nanoparticles, which was observed as 95% at 262.76 °C. XRD investigation on cisplatin-loaded PEGylated chitosan nanoparticles exhibited distinct peaks at 2θ as 9.7°, 20.4°, 22.1°, 25.3°, 36.1°, 38.1°, 39.5°, 44.3°, and 64.5°, confirming crystalline structure. The 1H NMR analysis showed the fingerprint region of cisplatin-loaded PEGylated chitosan nanoparticles as 0.85, 1.73, and 1.00 ppm in the proton dimension and de-shielded proton peaks appeared at 3.57, 3.58, 3.58, 3.59, 3.65, 3.67, 3,67, 3,67, 3.70, 3.71, 3.77, 3.78 and 4.71 ppm. The 13C NMR spectrum showed specified peaks at 63.18, 69.20, and 70.77 ppm. The FT-IR spectra of cisplatin loaded PEGylated nanoparticles show the existence of many fingerprint regions at 3186.52, 2931.68, 1453.19, 1333.98, 1253.71, 1085.19, 1019.60, 969.98, 929.53, 888.80, 706.13, and 623.67 cm-1. The drug release kinetics of cisplatin loaded PEGylated chitosan nanoparticles showed zero order kinetics with 48% of drug release linearity fashion which has R2 value of 0.9778. Studies on the MCF-7 ATCC human breast cancer cell line in vitro revealed that the IC50 value 82.08 µg /mL. Injectable nanoparticles had good physicochemical and cytotoxic properties. This method is novel since the application of the PEGylation processes leads to an increased solubility of chitosan nanoparticles at near neutral pH.

Explicit mechanistic insights of Prosopis juliflora extract in streptozotocin-induced diabetic rats at the molecular level.

Background: The Ancient system of medicine showed the limelight on the use of herbal remedies and was found to possess minimal side effects and acceptable therapeutic outcomes. In this context, Prosopis juliflora gained importance in managing chronic diseases such as cancer, dermatological diseases, and chronic inflammatory disorders. Hence, P. juliflora was selected for further investigation associated with diabetes and inflammation. Aim: The present study aimed to evaluate the anti-diabetic activity in chemically induced experimental rats and explore the nature of phytocomponents that may produce this activity. Methods: Experimentally, diabetes was induced by a single administration of streptozotocin at 50 mg/kg intraperitoneally in Wistar rats. The animals were treated orally with P. juliflora at low and high doses (200 and 400 mg/kg) for 10 days. Blood collected from the retro-orbital plexus was analyzed for parameters like blood glucose levels, insulin, adiponectin, Keap1 and Nrf2. PPAR-γ, AMPK and GLUT 2 levels were analyzed in the pancreatic tissue. Besides, at the end of the experiment, animals were sacrificed, and the pancreatic tissue sections were subjected for histopathological, morphometrical and immune histochemical exploration. The phytochemical composition of the plant was investigated by GC-MS. Results: The administration of P. juliflora higher dose showed a significant decrease (**p< 0.001) in blood glucose levels with a rise in adiponectin, PPARγ, Keap1, Nrf2, Glut 2, and AMPK significantly (**p< 0.001). The inflammatory cytokine TNFα was also estimated and was found to be lowered significantly (**p< 0.001) in test drug-treated animals. Furthermore, in the pancreatic tissue, the number of Islets, the area, and the number of ß-cells were improved significantly with the sub-chronic treatment of P. juliflora extract. The structure and function of ß-cells were also revamped. Conclusion: The study results demonstrated a significant effect of P. juliflora on glycemic status, inflammatory condition, and the architecture of pancreatic tissue. In the identification and isolation process by GC MS, it was noticed that P. juliflora contained few phytochemical constituents from which it might be considered a promising drug for type 2 diabetes mellitus.

Knowledge, perceptions, and readiness of telepharmacy among community pharmacists.

Telepharmacy is a practical part of telemedicine that refers to providing pharmaceutical services within the scope of the pharmacist's obligations while maintaining a temporal and spatial distance between patients, users of health services, and healthcare professionals. The present study was a cross-sectional study conducted among community pharmacists in Saudi Arabia between March and May 2022 to assess their knowledge, perceptions, and readiness for telepharmacy. The survey was filled out by 404 respondents. The majority of respondents were male (59.90%) and the age of more than half of them was between 30 and 39 years old (54.46%). Most participants worked in urban areas (83.66%), and 42.57% had less than five years of experience in a pharmacy. Most participants agreed that telepharmacy is available in Saudi Arabia (82.67%). Approximately 70% of pharmacists felt that telepharmacy promotes patient medication adherence, and 77.72% agreed that telepharmacy increases patient access to pharmaceuticals in rural areas. More than 72% of pharmacists said they would work on telepharmacy initiatives in rural areas for free, and 74.26% said they would work outside of usual working hours if necessary. In the future, this research could aid in adopting full-fledged telepharmacy pharmaceutical care services in Saudi Arabia. It could also help academic initiatives by allowing telepharmacy practice models to be included as a topic course in the curriculum to prepare future pharmacists to deliver telepharmacy services.

Novel spirooxindole based benzimidazole scaffold: In vitro, nanoformulation and in vivo studies on anticancer and antimetastatic activity of breast adenocarcinoma.

The present work provided in vitro anticancer investigation of novel spirooxindole based benzimidazole scaffold SP1 and its nanoformulation with in vivo evaluation of anticancer and antimetastatic activity as potential drug for breast adenocarcinoma. The synthesized compound SP1 exhibited potent growth inhibitory efficacy against four types of human cancer (breast, prostate, colon and lung) cell lines with IC50 = 2.4, 3.4, 7.24 and 7.81 µM and selectivity index 5.79, 4.08, 1.93 and 1.78 respectively. Flow cytometric analysis illustrated that SP1 exhibited high apoptotic effect on all tested cancer cell lines (38.22-52.3 %). The mode of action of this promising compound was declared by its ability to upregulate the gene expression of p21 (2.29-3.91 folds) with suppressing cyclin D (1.9-8.93 folds) and NF-κB (1.26-1.44 fold) in the treated cancer cells. Also, it enhanced the protein expression of apoptotic marker p53 and moderate binding affinity for MDM2 (KD;7.94 µM). Notwithstanding these promising impressive findings, its selectivity against cancer cell lines and safety on normal cells were improved by nanoformulation. Therefore, SP1 was formulated as ultra-flexible niosomal nanovesicles (transethoniosomes). The ultra-deformability is attributable to the synergism between ethanol and edge activators in improving the flexibility of the nanovesicular membrane. F8 exhibited high deformability index (DI) of (23.48 ± 1.4). It was found that % SP1 released from the optimized transethoniosomal formula (F8) after 12 h (Q12h) was 84.17 ± 1.29 % and its entrapment efficiency (%EE) was 76.48 ± 1.44 %. Based upon the very encouraging and promising in vitro results, an in vivo study was carried out in female Balb/c mice weighing (15-25 g). SP1 did halt the proliferation of breast cancer cells as well as suppressed the metastasis in other organs like liver, lung and heart.

Role of cinnamon oil against acetaminophen overdose induced neurological aberrations through brain stress and cytokine upregulation in rat brain.

Acetaminophen (APAP) is a well-known antipyretic and analgesic medicine. It is safe at therapeutic suggested level while overdose initiates oxidative stress and inflammation mediated neurochemical alteration in the brain. The aim of this study was to investigate the role of cinnamon oil (CO), which possesses potent antioxidant and anti-inflammatory activities against an overdose of APAP that induced oxidative stress and inflammation in male albino rats. APAP treated rats showed significant elevation of thiobarbituric acid-reactive substances (TBARS) and decreased level of GSH in brain tissue, which is recognized as a biomarker of oxidative stress. Antioxidant enzymes GPx, GR, SOD, and CAT activity was depleted in APAP group along with neurotoxicity biomarkers such as Na+-K+-ATPase and increased activity of acetylcholinesterase (AchE), monoamine oxidase (MAO), and upregulated pro-inflammatory cytokine was observed. CO significantly protected the diminished activity of the antioxidant enzyme and suppressed the upregulated cytokines in brain tissue. CO also attenuated the activity of neurotoxicity biomarker enzyme, decreased TBARS content, and an increased level of GSH. The present findings perceptibly confirmed that the nutraceutical property of CO ameliorates APAP induced oxidative stress and inflammation. Therefore, our findings suggested that CO could be an alternative nutraceutical substitute in APAP overdose poisoning.

Tricyclodecan-9-yl-Xanthogenate (D609): Mechanism of Action and Pharmacological Applications.

Tricyclodecan-9-yl xanthogenate (D609) is a synthetic tricyclic compound possessing a xanthate group. This xanthogenate compound is known for its diverse pharmacological properties. Over the last three decades, many studies have reported the biological activities of D609, including antioxidant, antiapoptotic, anticholinergic, anti-tumor, anti-inflammatory, anti-viral, anti-proliferative, and neuroprotective activities. Its mechanism of action is extensively attributed to its ability to cause the competitive inhibition of phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) and sphingomyelin synthase (SMS). The inhibition of PCPLC or SMS affects secondary messengers with a lipidic nature, i.e., 1,2-diacylglycerol (DAG) and ceramide. Various in vitro/in vivo studies suggest that PCPLC and SMS inhibition regulate the cell cycle, block cellular proliferation, and induce differentiation. D609 acts as a pro-inflammatory cytokine antagonist and diminishes Aß-stimulated toxicity. PCPLC enzymatic activity essentially requires Zn2+, and D609 might act as a potential chelator of Zn2+, thereby blocking PCPLC enzymatic activity. D609 also demonstrates promising results in reducing atherosclerotic plaque formation, post-stroke cerebral infarction, and cancer progression. The present compilation provides a comprehensive mechanistic insight into D609, including its chemistry, mechanism of action, and regulation of various pharmacological activities.

The Protective Effects of Sesamin against Cyclophosphamide-Induced Nephrotoxicity through Modulation of Oxidative Stress, Inflammatory-Cytokines and Apoptosis in Rats.

Cyclophosphamide is an anticancer drug with a wide spectrum of clinical uses, but its typical side effects are multiple complications, including nephron toxicity. The possible molecular mechanism of the nephroprotective action of sesamin (SM) against cyclophosphamide (CP) induced renal toxicity was investigated in rats by understanding oxidative stress and inflammatory cytokines. In this study, rats were arbitrarily grouped into the following four groups: a normal control group (CNT); a CP-induced toxicity group; a treatment group with two doses of sesamin SM10 and SM20; a group with sesamin (SM20) alone. A single dose of CP (150 mg/kg body, i.p.) was administered on day 4 of the experiments, while treatment with SM was given orally for seven days from day 1. The group treated with SM showed a significant protective effect against CP-induced renal damage in rats. Treatment with SM significantly increased the antioxidant enzymes (GSH, CAT, and SOD) and reduced malondialdehyde (MDA) levels. Thus, SM significantly overcame the elevated kidney function markers (creatinine, blood urea nitrogen, and uric acid) by attenuating oxidative stress. The SM also significantly reduced the elevated cytokines (IL-1ß and TNFα) and caspase-3 in the treated group. Histopathological studies confirmed the protective effect of sesamin (SM) on CP-induced nephrotoxicity. In conclusion, the current findings support the nephroprotective effect of sesamin against CP-induced renal injury.

Zingerone Attenuates Carfilzomib-Induced Cardiotoxicity in Rats through Oxidative Stress and Inflammatory Cytokine Network.

Carfilzomib (CFZ) is an anticancer medication acting as a selective proteasome inhibitor. However, it can cause cardiovascular problems, increasing mortality and morbidity. This study aimed to investigate whether zingerone (ZRN) could help reduce carfilzomib-induced cardiotoxicity in Wistar albino rats. Rats were divided into five groups of six animals each. The first group received normal saline as a control (NC); the second group received multiple doses (six) of CFZ (4 mg/kg) intraperitoneally (IP); the third and fourth groups received zingerone (50 mg/kg and 100 mg/kg oral) along with six doses of CFZ for 16 days; and the fifth group received only 100 mg/kg zingerone orally. Hematological, biochemical, oxidative stress, and histopathological studies confirmed the findings of CFZ-induced cardiotoxicity. We found that ZRN significantly attenuated the effects of CFZ on oxidative stress by enhancing the antioxidant properties of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Additionally, ZRN reduces inflammatory cytokines and apoptotic markers, such as IL-1ß, IL-6, TNFα, and caspase-3. Overall, zingerone prevents carfilzomib-induced cardiotoxicity in rats, as evidenced by histopathological studies.

Ameliorative effect of chitosan nanoparticles against carbon tetrachloride-induced nephrotoxicity in Wistar rats.

CONTEXT: Chitosan is a biocompatible polysaccharide that has been widely exploited in biomedical and drug delivery applications. OBJECTIVE: This study explores the renoprotective effect of chitosan nanoparticles in vivo in rats. MATERIALS AND METHODS: Chitosan nanoparticles were prepared via ionotropic gelation method, and several in vitro characterizations were performed, including measurements of particle size, zeta potential, polydispersity index, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy (TEM) imaging. Wistar rats were divided randomly into four groups; negative control, CCl4-induced nephrotoxicity (untreated), and two groups receiving CCl4 + chitosan NPs (10 and 20 mg/kg) orally for 2 weeks. The renoprotective effect was assessed by measuring oxidative, apoptotic, and inflammatory biomarkers, and via histopathological and immunohistochemical examinations for the visualization of NF-κB and COX-2 in renal tissues. RESULTS: Monodisperse spherical nanosized (56 nm) particles were successfully prepared as evidenced by dynamic light scattering and TEM. Oral administration of chitosan nanoparticles (10 and 20 mg/kg) concurrently with CCl4 for 2 weeks resulted in 13.6% and 21.5% reduction in serum creatinine and increase in the level of depleted reduced glutathione (23.1% and 31.8%), respectively, when compared with the positive control group. Chitosan nanoparticles (20 mg/kg) revealed a significant (p ˂ 0.05) decrease in malondialdehyde levels (30.6%), tumour necrosis factor-α (33.6%), interleukin-1ß (31.1%), and caspase-3 (36.6%). CONCLUSIONS: Chitosan nanoparticles afforded significant protection and amelioration against CCl4-induced nephrotoxicity. Thus, chitosan nanoparticles could afford a potential nanotherapeutic system for the management of nephrotoxicity which allows for broadening their role in biomedical delivery applications.

The prevalence of hypercholesterolemia and associated risk factors in Al-Kharj population, Saudi Arabia: a cross-sectional survey.

BACKGROUND: Hypercholesterolemia (HC) is an important precursor to many cardiovascular, cerebrovascular, and peripheral vascular diseases. A report conducted by the American Heart Association showed the prevalence of HC to be 11.9%, with around 28.5 million adults age ≥ 20 years having high cholesterol levels. This study aimed to evaluate the prevalence of HC and its associated risk factors among the general population of Al-Kharj, Saudi Arabia. METHOD: A cross-sectional study was conducted on the general population of Al-Kharj, Saudi Arabia in 2016. The representative sample consisted of 1019 individuals, who all participated on a voluntary basis. The statistical analysis was performed using SPSS version 25. RESULTS: The results of this study showed the prevalence of HC in the sample to be 12.5%. There was a significant moderate positive association between increasing age and the prevalence of HC (r = 0.240, P < 0.0001). Males had a significantly higher prevalence of HC (56.7%) compared to their female counterparts (43.3%) (X2 = 23.093, P ≤ 0.0001). BMI was positively and significantly associated with high cholesterol status. Participants in the overweight category had a significantly higher risk of HC (OR = 1.727; 95% CI = 1.58-1.914; P = 0.046). The non-obese (< 25 kg/m2) participants had an inverse significant association with the risk of hypercholesterolemia. (OR = 0.411; 95% CI = 0.216-0.783; P = 0.007). CONCLUSION: In this population-based study, the predominant risk factors of HC in Al-Kharj region were being of a Saudi nationality, male, having obesity, being unemployed, and being a civilian worker. There is a clear need for future screening studies of HC, as most previous studies have reported contradictory prevalence data (because they were conducted in different regions of KSA). Furthermore, well-designed prospective cohort studies are needed in the future to assess how the association between lifestyle behavioural factors such as dietary intake patterns and levels of physical activity may affect the relative risk of HC status.

Characteristics and recurrence of pterygium in Saudi Arabia: a single center study with a long follow-up.

BACKGROUND: This study described the clinical features of patients with pterygium and analyzed the recurrence rate of conjunctival autografting alone, conjunctival autografting combined with intraoperative mitomycin C, and amniotic membrane grafting. METHODS: A retrospective cohort study of primary pterygium was conducted between January 2017 and February 2020. Factors associated with pterygium severity and recurrence were analyzed by univariate analysis and logistic regression models. RESULTS: The study included 292 patients with an average age of 53.3 ± 14.1 years, while the number of operated cases was 94. Pterygia involving the cornea were observed in 55 % of the cases. The overall rate of recurrence for the three procedures was 17 %. The average time of recurrence was 14.2 ± 11.9 months, with 37 % of the recurrences occurring after the first year. The only factor associated with a significant risk of recurrence was dry eye disease in both univariate (p = 0.021) and multivariate analysis (p = 0.026). The recurrence rates following conjunctival autografting with and without mitomycin C were 15.6 and 15.8 %, respectively. The recurrence rate following the amniotic membrane graft was  twofold (OR= 2.02)  (27 %) that following the conjunctival autograft (15.8 %). CONCLUSIONS: The only factor associated with the recurrence of pterygium was dry eye disease. More than one-third of recurrences developed after the first year, which stresses the importance of a long follow-up. The recurrence rate in our study following conjunctival graft was slightly higher compared to the literature mainly due to differences in study areas, populations, and follow-up periods.

Inflammation and Alzheimer's Disease: Mechanisms and Therapeutic Implications by Natural Products.

Alzheimer's disease (AD) is a neurodegenerative disorder with no clear causative event making the disease difficult to diagnose and treat. The pathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and widespread neuronal loss. Amyloid-beta has been extensively studied and targeted to develop an effective disease-modifying therapy, but the success rate in clinical practice is minimal. Recently, neuroinflammation has been focused on as the event in AD progression to be targeted for therapies. Various mechanistic pathways including cytokines and chemokines, complement system, oxidative stress, and cyclooxygenase pathways are linked to neuroinflammation in the AD brain. Many cells including microglia, astrocytes, and oligodendrocytes work together to protect the brain from injury. This review is focused to better understand the AD inflammatory and immunoregulatory processes to develop novel anti-inflammatory drugs to slow down the progression of AD.

The possible role of methylglyoxal metabolism in cancer.

Tumours reprogram their metabolism to acquire an evolutionary advantage over normal cells. However, not all such metabolic pathways support energy production. An example of these metabolic pathways is the Methylglyoxal (MG) one. This pathway helps maintain the redox state, and it might act as a phosphate sensor that monitors the intracellular phosphate levels. In this work, we discuss the biochemical step of the MG pathway and interrelate it with cancer.

Psychological predictors of chronic pain in Al Kharj region, Saudi Arabia.

BACKGROUND: Psychological distress is one of the major determinants for the experience progression, and recovery of chronic pain. However, it is unclear whether physical pain in specific body sites could be predictive of psychological illness. In this study, we aim to investigate the link between chronic pain in specific anatomical sites and psychological distress represented in the General Health Questionnaire-12 (GHQ-12 items). METHODS: A population-based cross-sectional study was conducted in Al Kharj region of Saudi Arabia. We included 1003 participants. Data were collected using the GHQ-12, and a subjective report on eight anatomical pain sites. Data analysis used statistical software SPSS version 26.0 for Windows statistical package. RESULTS: Chronic musculoskeletal pain in the neck and head regions was significantly associated with higher psychological distress. Other sites (back, lower limb, chest, abdominal and upper limb pain) were not associated with psychological distress. In multiple regression analysis, chronic 'general' pain was significantly associated with higher psychological distress (unstandardized Beta regression coefficient = 2.568; P < 0.0001). The patients with younger age were more likely to develop negative psychological disorders (unstandardized Beta = - 3.137; P = 0.038). Females were more likely to have higher psychological distress than males (unstandardized Beta = 2.464, P = 0.003). Single (not-married) people have a higher risk of psychological distress than married people (unstandardized Beta = 2.518, P = 0.025). Also, job type/status whether being unemployed (not working) or 'civilian' (civil servant/worker) was positively and significantly associated with an increased probability of psychological distress (unstandardized Beta = 1.436, P = 0.019). CONCLUSION: Chronic 'general' pain was significantly associated with negative psychological disorders. The government of Saudi Arabia needs to focus on patients with chronic 'general' pain, females, young and unmarried individuals as potentially 'high-risk' population subgroups for adverse psychological disorders, and subsequent long-term complications.