Mechanistic insights into Retama raetam's anti-proliferative and pro-apoptotic effects in A549 lung cancer cells: targeting PI3K/Akt pathway and ROS production.

Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths worldwide. This study investigates the molecular mechanisms behind the anti-cancer effects of the tropical desert plant Retama raetam (R. raetam) on the A549 NSCLC cell line. The research examined R. raetam's anti-proliferative effects, cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and cell morphology in NSCLC A549 and L-132 cells. In addition, the influence of R. raetam on DNA fragmentation, apoptotic signaling, and PI3K/Akt pathways for its anti-cancer mechanism was examined. Our results indicated that R. raetam's effects were dose- and time-dependent to exhibit anti-proliferative effects on A549 cells. R. raetam treatment promoted apoptotic cell death cycle arrest, increased apoptotic cells, depolarized the mitochondrial membrane, and induced morphological alterations in cells and nuclei. It also inhibited A549 cell migration (P < 0.05), colonization, and invasiveness. Moreover, the study demonstrated that R. raetam treatment resulted in the upregulation of Bax expression, downregulation of Bcl-2 expression, and apoptotic fragmented DNA in A549 cells. The top five bioactive compounds derived from R. raetam exhibited molecular interactions that inhibit PIK3CA and AKT1. This inhibition leads to an increased frequency of apoptosis and subsequent death of cancer cells. Additionally, R. raetam extract induced an increase in ROS formation and cytochrome c levels, indicating that its toxic effects on A549 cells involve both ROS-dependent cytotoxicity through the disruption of mitochondrial transmembrane potential ΔΨm and ROS-independent cell cycle arrest through downregulation BCL-2, PARP, E-Cadherin, PI3K, and Akt expressions pathways.

Comorbidities, medications, depression, and physical performance measures associated with severe cognitive impairments in community-dwelling adults.

Cognitive impairment negatively impacts health, psychological, social, and economic domains. Cognitive impairment commonly affects physical functions in older adults, whereas these are deteriorated. However, the prevalence and associated factors of cognitive impairment among community-dwelling adults in Saudi Arabia have not been investigated yet. This study aimed to examine the prevalence of severe cognitive impairment and its associated factors in community-dwelling older adults in Saudi Arabia. This cross-sectional study involved adults aged ≥50 years. Demographic data and clinical data, including number of medications and body mass index (BMI), were collected. Cognitive impairment and depressive symptoms were measured using Arabic versions of the Montreal Cognitive Assessment (MoCA) and Patient Health Questionnaire-9 (PHQ-9), respectively. The participants were divided into severe cognitive impairment and mild cognitive impairment or normal cognitive function groups based on a score of <20 or ≥20, respectively, using the MoCA. Physical measures included dynamic gait index (DGI) scores, timed up-and-go (TUG), 5 times sit-to-stand (5XSST), functional reach test, and 6-minute walk test. A total of 206 participants (female: n = 96) were included. The prevalence of severe cognitive impairment in the community-dwelling older adults was 12.6%. The number of chronic conditions (odds ratio [OR]: 2.31, p<0.001), number of medications (OR: 1.36, p = 0.003), and depressive symptoms using PHQ-9 (OR: 1.11, p = 0.009) were significantly associated with severe cognitive impairment after adjustment for other covariates, including age, sex, and BMI. Based on the physical function measures, only the scores for DGI (OR: 0.86, p = 0.003), TUG (OR: 1.16, p = 0.035) and 5XSST (OR: 1.25, p <0.001) were significantly associated with severe cognitive impairment. This study revealed a high prevalence of severe cognitive impairment among community-dwelling adults in Saudi Arabia. Its major risk factors include depressive symptoms, number of chronic conditions and medications, and physical measures, including DGI, TUG, and 5XSST.

Morpholine-tethered Novel Hydrazones as Promising Non-peptidic Prolyl Oligopeptidase (POP) Inhibitors: Synthesis In Vitro and In Silico Studies.

INTRODUCTION: Prolyl oligopeptidase (POP) is a pivotal druggable target implicated in diverse biological processes and linked to the development of various ailments, including neurodegenerative disorders. While conventional peptide-based inhibitors have been a centerpiece, their limitations, such as restricted bioavailability, necessitate exploration of non-peptidic inhibitors for their therapeutic potential. METHOD: This study focuses on designing, synthesizing, and assessing morpholine-based hydrazones targeting the catalytic serine residue of POP. The hydrazones (5a-o), reported as moderately potent analogs compared to the renowned Z-Pro-Prolinal, demonstrated in vitro POP inhibition with IC50 values ranging from 13.60 ± 2.51 to 36.51 ± 1.82 µM. The derivative 5h, with an IC50 of 13.60 ± 2.51 µM, emerged as the most potent inhibitor. RESULTS: Moreover, the in vitro kinetic study of compound 5h indicated that it exhibited concentration-dependent type of inhibition. in silico docking studies of 5h revealed robust interactions in the POP enzyme's active site, yielding a docking score of -6.30 Kcal/- mol, consistent with experimental results. CONCLUSION: All findings underscored the potential of synthesized derivatives for drug development.

In silico study of some plant compounds as potential anticancer agents targeting MALT1 allosteric domain.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is the only human paracaspase, that serves as an adaptor protein and controls substantial genes expressed in the activation, proliferation of lymphocyte, and immune reactions by triggering the IKK/NF-kB signaling pathway. However, unusual MALT1-mediated NF-kB signaling pathway has been identified in multiple diseases like cancer, therefore making MALT1 a promising therapeutic target. There are scanty numbers of MALT1 inhibitors, thus the need to discover more compounds with less or no toxicity issue, that are cheap and pharmacologically efficient is of pertinence. Hence, our present study was to identify phyto-small molecules that could bind the allosteric interface of MALT1 using in silico methods. Total of 34 plant molecules were selected and screened for druglikeness, after which they were docked via Maestro 11.1 against the allosteric site of MALT1. The molecule with a binding score (kcal/mol) better than the control drug was subjected to molecular dynamics (MD) simulations of 100 ns via Desmond, free energy perturbations, principal component and Pearson correlation analyses. Our findings from this computational study presents cyanidin (-8.822 kcal/mol) as better binder to the allosteric site of MALT1 based on the molecular docking and pharmacokinetic profiling than thioridazine. Similarly, cyanidin-MALT1 complex showed significant stability and exhibiting contacts with critical amino acid residues in the site of interest than thioridazine-MALT1 complex. Hence, cyanidin is a potential allosteric inhibitor of MALT1. However, an urgent need for in vitro and in vivo validations is required to ascertain the efficacy of cyanidin in the fight against cancer and other MALT1-related diseases.

Impact of biological therapies on laboratory outcomes and FEV1 in patients with severe eosinophilic asthma with chronic rhinosinusitis: a real-life study from Saudi Arabia.

                                                                 Abstract Background: Few studies have addressed the effects of biological therapies on laboratory outcomes and changes in FEV1 in patients with severe asthma (SA) and chronic rhinosinusitis (CRS). We aimed to study the effect of three biological therapies on laboratory outcomes and FEV1 in Saudi Arabian patients with SA and CRS. METHODS: From March to September 2022, a retrospective observational cohort study was undertaken at the severe asthma clinics of the Armed Forces Hospital-Southern Region (AFHSR) and King Khalid University Hospital, Abha, Saudi Arabia, to delineate the effects of 3 biological therapies (benralizumab, dupilumab, and omalizumab) in adults with SA and concomitant CRS in terms of FEV1 and laboratory parameters (serum IgE and eosinophilic counts). RESULTS: Eighty patients were enrolled, with a mean age of 46.68. There were 45 (56%) females and 35 (44%) males. There were significant improvements in FEV1 and laboratory parameters (serum IgE and eosinophilic counts) after 6 &12 months of biological therapies compared to pre-biological therapies (p<0.001, each). The response was different among different biological therapies. The improvements in FEV1, serum IgE, and eosinophilic counts were manifest with benralizumab and dupilumab but not with omalizumab. CONCLUSIONS: Results from the first study from two large Saudi Arabian tertiary centers for patients with severe asthma and chronic rhinosinusitis agree with and support those of worldwide real-life ones. One-year follow-up of patients with SA and CRS showed the effectiveness of benralizumab and dupilumab, but not omalizumab, regarding FEV1, serum IgE, and eosinophilic counts. Further prospective multicenter studies are warranted.

Modulation of Cd carriers by innovative nanocomposite (Ca+Mg) and Cd-resistance microbes (Bacillus pumilus): a mechanistic approach to enhance growth and yield of rice (Oryza sativa L.).

Cadmium (Cd) is a well-known pollutant in agricultural soil, affecting human health through the food chain. To combat this issue, Ca + Mg (25 mg L-1) nanocomposite and Bacillus pumilus, either alone or combined, were applied to rice plants under Cd (5 mg kg-1, 10 mg kg-1) contamination. In our study, growth and yield traits demonstrated the beneficial influence of Ca + Mg and B. pumilus application in improving rice defense mechanism by reducing Cd stress. Combined Ca + Mg and B. pumilus application increased SPAD (15), total chlorophyll (18), chlorophyll a (11), chlorophyll b (22), and carotenoids (21%) with Cd (10 mg kg-1), compared to the application alone. Combined Ca + Mg and B. pumilus application significantly regulated MDA (15), H2O2 (13), EL (10), and O2 •- (24%) in shoots under Cd (10 mg kg-1), compared to the application alone. Cd (10 mg kg-1) increased the POD (22), SOD (21), APX (12), and CAT (13%) in shoots with combined Ca + Mg and B. pumilus application, compared to the application alone. Combined Ca + Mg and B. pumilus application significantly reduced Cd accumulation in roots (22), shoots (13), and grains (20%) under Cd (10 mg kg-1), compared to the application alone. Consequently, the combined application of Ca + Mg and B. pumilus is a sustainable solution to enhance crop production under Cd stress.

Suppression of glomerular damage, inflammation, apoptosis, and oxidative stress of acute kidney injury induced by cyclophosphamide toxicity using resveratrol in rat models.

Cyclophosphamide (CP) is a chemotherapy drug that can be used to treat different types of cancers, but its nephrotoxicity effects restrict its usage in clinical settings. Currently, we examined whether the polyphenolic antioxidant and anti-inflammatory compound, resveratrol (RES), can protect against CP-induced nephrotoxicity. Twenty male mature Sprague-Dawley rats were divided into 4 groups of equal size: control group, RES group which received RES (20 mg/kg) for 15 consecutive days, CP group which received CP as a single dose (150 mg/kg) on day 16, and CP+RES group which was similar of the RES and CP groups. Tissue samples were obtained for the stereological, immunohistochemical, biochemical, and molecular evaluations. Findings showed that the numerical density of glomerulus, total volumes and interstitial tissue volumes of kidney, antioxidative biomarkers concentrations (CAT, GSH, SOD), and expression levels of OCT2 gene were notably greater in the CP+RES group than the CP group (P<0.05). During treatment, there was a significant decrease in the serum levels of the urea and creatinine, the densities of apoptotic and inflammatory cells, as well as levels of MDA and proinflammatory cytokines (IL-1ß, TNF-α, and PFN1) in the CP+RES group than the CP group (P<0.05). We deduce that giving RES can suppress of glomerular damage, inflammation, apoptosis, and oxidative stress of acute kidney injury induced by CP toxicity.

Assessing variability and hydrochemical characteristics of groundwater fluoride contamination and its associated health risks in East Singhbhum district of Jharkhand, India.

Groundwater pollution caused by fluoride is a significant concern for the global population owing to its toxicity, which has negative health consequences. Industrial discharges, agricultural practices, and improper waste disposal are primary concerns in evaluating the degree of fluoride contamination in the selected districts of Eastern India. In a targeted area sampling approach, exactly 196 samples were collected during pre- and post-monsoon, and precise fluoride detection was performed using Ion-Selective Electrodes. Fluoride levels in pre-monsoon water were observed within a range of 0.02 to 2.7 mg/L, with an average abundance of 0.4 ± 0.50. In post-monsoon, the concentration ranged from 0.02 to 4.7 mg/L (mean 0.53 ± 0.60). The study found that 97 % of groundwater samples had acceptable fluoride levels within the 1.5 mg/L limit during pre and post-monsoon. Moreover, approximately 87 % of the samples exhibit fluoride content below the 1 mg/L limit. The hazard quotient was observed to be 0.17 to 0.58 in adults, 0.23 to 0.79 in children and 0.36 to 1.26 in infants during pre-monsoon, whereas 0.05 to 0.55 in adults, 0.12 to 0.74 in children and 0.11to 1.19 in infants during post monsoon. The above data indicates that infants had the highest risk of fluoride exposure, with a significant negative correlation between fluoride and calcium ions. Fluoride had minimal to no link with other ions, a modest positive correlation with sulfate, and a weak negative relationship with overall hardness and alkalinity across both seasons. The present study contributes towards the identification of fluoride levels in various areas, making society aware of water contamination and its health impacts.

Genetic diversity of tick-borne zoonotic pathogens in ixodid ticks collected from small ruminants in Northern Pakistan.

Mapping tick distribution and pathogens in unexplored areas sheds light on their importance in zoonotic and veterinary contexts. In this study, we performed a comprehensive investigation of the genetic diversity of tick and tick-borne pathogens (TBPs) detection infesting/infecting small ruminants across northern Pakistan. We collected 1587 ixodid ticks from 600 goats and sheep, an overall tick infestation rate of 50.2 %. Notably, gender-based infestation rates were higher in female goats and sheep compared to their male counterparts. Age-wise analysis showed that the tick infestation rate was higher in older animals. This study identified 11 ixodid tick species within three genera: Hyalomma, Haemaphysalis, and Rhipicephalus, which were taxonomically classified using 16S rRNA and cytochrome oxidase I (cox1) molecular markers. Sequence analysis indicated that reported ticks are similar to ixodid species found across various Asian and African countries. Tick-borne pathogens were detected by amplifying 16S rRNA and citrate synthase (gltA) for bacterial pathogens and 18S rRNA for apicomplexan parasites. The present study reported a diverse array of TBPs in ticks from the study area, with Rickettsia massiliae (24.5 %) and Theleria ovis (16.4 %) as the most prevalent bacterial and apicomplexan pathogens. Phylogenetically, detected TBPs shared evolutionary relatedness with identical TBPs from old and new world countries. These findings highlight the presence of zoonotic TBPs in ixodid ticks from Pakistan. In addition, it also provides a foundation for future epidemiological research on ticks and TBPs, emphasizing their relevance in both zoonotic and veterinary contexts.

Vinpocetine and Lactobacillus improve fatty liver in rats: role of adiponectin and gut microbiome.

Therapeutics that interfere with the damage/pathogen-associated molecular patterns (DAMPs/PAMPs) have evolved as promising candidates for hepatic inflammation like that occurring in non-alcoholic fatty liver disease (NAFLD). In the current study, we examined the therapeutic impact of the phosphodiesterase-1 inhibitor vinpocetine (Vinpo), alone or when combined with Lactobacillus, on hepatic abnormalities caused by a 13-week high-fat diet (HFD) and diabetes in rats. The results show that Vinpo (10 and 20 mg/kg/day) dose-dependently curbed HFD-induced elevation of liver injury parameters in serum (ALT, AST) and tissue histopathology. These effects were concordant with Vinpo's potential to ameliorate HFD-induced fibrosis (Histological fibrosis score, hydroxyproline, TGF-ß1) and oxidative stress (MDA, NOx) alongside restoring the antioxidant-related parameters (GSH, SOD, Nrf-2, HO-1) in the liver. Mechanistically, Vinpo attenuated the hepatocellular release of DAMPs like high mobility group box (HMGB)1 alongside lowering the overactivation of the pattern recognition receptors including, toll-like receptor (TLR)4 and receptor for advanced glycation end-products (RAGE). Consequently, there was less activation of the transcription factor nuclear factor-kappa B that lowered production of the proinflammatory cytokines TNF-α and IL-6 in Vinpo-treated HFD/diabetes rats. Compared to Vinpo treatment alone, Lactobacillus probiotics as adjunctive therapy with Vinpo significantly improved the disease-associated inflammation and oxidative stress injury, as well as the insulin resistance and lipid profile abnormalities via enhancing the restoration of the symbiotic microbiota. In conclusion, combining Vinpo and Lactobacillus probiotics may be a successful approach for limiting NAFLD in humans.

Clinical management of eye diseases: carotenoids and their nanoformulations as choice of therapeutics.

Eye diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), impose a substantial health cost on a worldwide scale. Carotenoids have emerged as intriguing candidates for pharmacological treatment of various disorders. Their therapeutic effectiveness, however, is hindered by poor solubility and vulnerability to degradation. Nanocarriers, such as nanoparticles, liposomes, and micelles, provide a transformational way to overcome these limits. This review explores the pharmacological potential of carotenoids, namely lutein, zeaxanthin, and astaxanthin, to treat several ocular disorders. The main emphasis is on their anti-inflammatory and antioxidant actions, which help to counteract inflammation and oxidative stress, crucial factors in the development of AMD and DR. The review evaluates the significant benefits of nano-formulated carotenoids, such as improved bioavailability, higher cellular absorption, precise administration to particular ocular tissues, and greater biostability, which make them superior to conventional carotenoids. Some clinical studies on the beneficial properties of carotenoids in eye diseases are discussed. Furthermore, safety and regulatory concerns are also taken into account. Ultimately, carotenoids, especially when created in their nano form, have significant potential for safeguarding eyesight and enhancing the overall well-being of several individuals afflicted with vision-endangering eye diseases.

Knowledge and willingness to donate kidney for transplantation among general population in Saudi Arabia.

INTRODUCTION: Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), offering a superior quality of life and extended survival compared to other renal replacement therapies. As the number of ESRD patients grows, so does the demand for organ transplants. The prevalence of ESRD is anticipated to escalate further due to the rising rates of diabetes mellitus (DM), hypertension (HTN), and obesity. Organ donation, particularly from living donors, remains the main source of transplants in the region, despite the notable underutilization of potential deceased donors' organs. The objective of this research is to assess the level of knowledge, attitudes, and willingness to donate kidneys among the general population, a pivotal step in addressing the organ shortage crisis. METHODS: This cross-sectional study was conducted in the Aseer region of Saudi Arabia using a previously validated questionnaire. The questionnaire collected demographic data and insights into general attitudes, knowledge, and beliefs about organ donation. Logistic regression was used to identify predictors of knowledge and willingness to donate. RESULTS: The study involved 705 participants, predominantly young adults with a high level of education. Awareness of kidney donation was high, and knowledge about donation was broad, especially regarding religious permissibility and awareness of the donor registry. However, only 25% expressed willingness to donate their kidneys, and a 4% were already registered as donors. Furthermore, higher educational level was not associated with higher odds of knowledge or willingness to donate. CONCLUSION: Despite the considerable awareness, actual donor registration rates were low, highlighting the necessity for targeted educational interventions and a deeper understanding of the cultural and socioeconomic barriers that exist.

Leveraging machine learning to enhance postoperative risk assessment in coronary artery bypass grafting patients with unprotected left main disease - A retrospective cohort study.

BACKGROUND: Risk stratification for patients undergoing coronary artery bypass surgery (CABG) for left main coronary artery (LMCA) disease is essential for informed decision-making. This study explored the potential of machine learning (ML) methods to identify key risk factors associated with mortality in this patient group. METHODS: This retrospective cohort study was conducted on 866 patients from the Gulf Left Main Registry who presented between 2015 and 2019. The study outcome was hospital all-cause mortality. Various machine learning models [logistic regression, random forest (RF), k-nearest neighbor, support vector machine, naïve Bayes, multilayer perception, boosting] were used to predict mortality, and their performance was measured using accuracy, precision, recall, F1 score, and area under the receiver operator characteristic curve (AUC). RESULTS: Nonsurvivors had significantly greater EuroSCORE II values (1.84 (10.08-3.67) vs. 4.75 (2.54-9.53) %, P<0.001 for survivors and nonsurvivors, respectively). The EuroSCORE II score significantly predicted hospital mortality (OR: 1.13 (95% confidence interval: 1.09-1.18), P<0.001), with an AUC of 0.736. RF achieved the best ML performance (accuracy=98, precision=100, recall=97 and F1 score=98). Explainable artificial intelligence using SHAP demonstrated the most important features as follows: preoperative lactate level, emergency surgery, chronic kidney disease (CKD), NSTEMI, nonsmoking status, and sex. QLattice identified lactate and CKD as the most important factors for predicting hospital mortality this patient group. CONCLUSION: This study demonstrates the potential of ML, particularly the Random Forest, to accurately predict hospital mortality in patients undergoing CABG for LMCA disease and its superiority over traditional methods. The key risk factors identified, including preoperative lactate levels, emergency surgery, chronic kidney disease, NSTEMI, nonsmoking status, and sex, provide valuable insights for risk stratification and informed decision-making in this high-risk patient population. Additionally, incorporating newly identified risk factors into future risk scoring systems can further improve mortality prediction accuracy.

Prevalence of Forward head posture among car and bike drivers and its relation with neck and cardiopulmonary health parameters- a cross-sectional study.

OBJECTIVES: This study aimed to evaluate and compare the prevalence of Forward Head Posture (FHP) in car and bike drivers, and its potential correlation with neck and cardiopulmonary parameters. METHODS: This cross-sectional study involved 400 participants from urban and suburban areas around Lucknow, Uttar Pradesh, India, including 200 car drivers and 200 bike drivers aged 18-65 years with a minimum five-year driving history. Neck health was assessed using measurements such as cervical range of motion and Neck Disability Index (NDI), cardiopulmonary parameters were evaluated through resting heart rate, blood pressure, and pulmonary function tests using the spirometry test, and FHP was assessed using Surgimap application. Statistical analysis was performed using IBM SPSS Statistics software (version 26.0) and included descriptive statistics, hypothesis testing, Chi-square or Fisher's exact test for binary data, and correlation analyses. RESULTS: The result show that difference in the mean FHP between car and bike drivers was statistically significant (p = 0.0001), indicating a higher prevalence of FHP among car drivers than among bike drivers. Correlation analyses revealed significant associations between FHP and neck health metrics, especially cervical flexion (r = 0.71, p<0.05), (r = 0.78, p<0.05) and left-side rotation (r = 0.56, p<0.05), (r = 0.61, p<0.05) in car and bike drivers. Among the cardiopulmonary parameters, significant correlations with FHP were observed in resting heart rate (r = 0.33, p<0.05), (r = 0.42, p<0.05), spirometry results FVC (r = 0.29, p<0.05), FEV1 (r = 0.22, p<0.05), and FVC (r = 0.31, p<0.05) for car and bike drivers. CONCLUSION: We observed a higher incidence of FHP in car drivers, indicating that a prolonged static posture may lead to greater postural deviation than dynamic movement during biking. This association suggests that FHP could have wide-reaching implications for systemic health, beyond musculoskeletal issues. These findings have the potential to influence preventative strategies and interventions aimed at improving the overall health outcomes for drivers.

Clinical outcomes of patients with cardiogenic shock complicating acute myocardial infarction: The Gulf-Cardiogenic Shock (G-CS) Registry.

BACKGROUND: There is a paucity of data regarding acute myocardial infarction (MI) complicated by cardiogenic shock (AMI-CS) in the Gulf region. This study addressed this knowledge gap by examining patients experiencing AMI-CS in the Gulf region and analyzing hospital and short-term follow-up mortality. METHODS: The Gulf-CS registry included 1,513 patients with AMI-CS diagnosed between January 2020 and December 2022. RESULTS: The incidence of AMI-CS was 4.1% (1513/37379). The median age was 60 years. The most common presentation was ST-elevation MI (73.83%). In-hospital mortality was 45.5%. Majority of patients were in SCAI stage D and E (68.94%). Factors associated with hospital mortality were previous coronary artery bypass graft (OR:2.49; 95%CI: 1.321-4.693), cerebrovascular accident (OR:1.621, 95%CI: 1.032-2.547), chronic kidney disease (OR:1.572; 95%CI1.158-2.136), non-ST-elevation MI (OR:1.744; 95%CI: 1.058-2.873), cardiac arrest (OR:5.702; 95%CI: 3.640-8.933), SCAI stage D and E (OR:19.146; 95CI%: 9.902-37.017), prolonged QRS (OR:10.012; 95%CI: 1.006-1.019), right ventricular dysfunction (OR:1.679; 95%CI: 1.267-2.226) and ventricular septal rupture (OR:6.008; 95%CI: 2.256-15.998). Forty percent had invasive hemodynamic monitoring, 90.02% underwent revascularization, and 45.80% received mechanical circulatory support (41.31% had Intra-Aortic Balloon Pump and 14.21% had Extracorporeal Membrane Oxygenation/Impella devices). Survival at 12 months was 51.49% (95% CI: 46.44- 56.29%). CONCLUSIONS: The study highlighted the significant burden of AMI-CS in this region, with high in-hospital mortality. The study identified several key risk factors associated with increased hospital mortality. Despite the utilization of invasive hemodynamic monitoring, revascularization, and mechanical circulatory support in a substantial proportion of patients, the 12-month survival rate remained relatively low.

Mitigating Acetaminophen-Induced Kidney Injury: The Protective Role of Grape Seed and Peanut Skin Extracts through the iNOS/CYP2E1 Pathway.

The rising number of acute kidney injury cases worldwide due to acetaminophen (APAP) emphasizes the critical need for effective prevention strategies to counteract APAP's detrimental effects. This study examined the kidney-protective capabilities of ethanolic extracts from grape seeds and peanut skins (GSEE and PSEE, respectively) in comparison with silymarin in rats that experienced an APAP overdose. The phenolic compounds in these extracts were measured by using high-performance liquid chromatography (HPLC). In the experiment, Sixty adult male albino rats were divided into five groups of 12. The Control group received 0.5 mL of saline via a gastric tube. Group II received acetaminophen (APAP, 640 mg/kg per day via a gastric tube) to induce renal injury, following Ucar et al. and Islam et al. Groups III, IV, and V received silymarin (50 mg/kg), grape seed extract (200 mg/kg), and peanut skin extract (200 mg/kg), respectively, along with 640 mg of APAP/kg per day for 21 days. Post APAP treatment, significant increases in serum urea and creatinine levels were noted, along with notable decreases in the percentage of body weight gain. Furthermore, there were increases in oxidative stress and inflammatory markers in the kidney tissues, including heightened mRNA expressions of renal iNOS and CYP2E1, which were confirmed through histological studies. The administration of GSEE, PSEE, and silymarin mitigated these adverse effects, likely due to their high phenolic content, which is recognized for its antioxidant and anti-inflammatory effects. GSEE, in particular, showed efficacy comparable to that of silymarin. Molecular docking studies revealed that APAP impeded critical enzymes essential for cellular antioxidant defense, whereas the bioactive compounds in the grape seed and peanut skin extracts effectively inhibited key enzymes and receptors involved in inflammation and oxidative stress. These findings suggest that GSEE and PSEE could serve as viable alternative treatments for kidney damage induced by APAP. Further research to isolate and identify these effective compounds is recommended.

Ceftriaxone and MC-100093 mitigate fentanyl-induced cardiac injury in mice: Preclinical investigation of its underlying molecular mechanisms.

Drug addiction is considered a worldwide concern and one of the most prevailing causes of death globally. Opioids are highly addictive drugs, and one of the most common opioids that is frequently used clinically is fentanyl. The potential harmful effects of chronic exposure to opioids on the heart are still to be elucidated. Although ß-lactam antibiotics are well recognized for their ability to fight bacteria, its protective effect in the brain and liver has been reported. In this study, we hypothesize that ß-lactam antibiotic, ceftriaxone, and the novel synthetic non-antibiotic ß-lactam, MC-100093, are cardioprotective against fentanyl induced-cardiac injury by upregulating xCT expression. Mice were exposed to repeated low dose (0.05 mg/kg, i.p.) of fentanyl for one week and then challenged on day 9 with higher dose of fentanyl (1 mg/kg, i.p.). This study investigated cardiac histopathology and target genes and proteins in serum and cardiac tissues in mice exposed to fentanyl overdose and ß-lactams. We revealed that fentanyl treatment induced cardiac damage as evidenced by elevated cardiac enzymes (troponin I). Furthermore, fentanyl treatment caused large aggregations of inflammatory cells and elevation in the areas and volumes of myocardial fibers, indicating hypertrophy and severe cardiac damage. Ceftriaxone and MC-100093 treatment, However, induced cardioprotective effects as evidenced by marked reduction in cardiac enzymes (troponin I) and changes in histopathology. Furthermore, ceftriaxone and MC-100093 treatment decreased the levels of hypertrophic genes (α-MHC & ß-MHC), apoptotic (caspase-3), and inflammatory markers (IL-6 & NF-κB). This study reports for the first time the cardioprotective effect of ß-lactams against fentanyl-induced cardiac injury. Further studies are greatly encouraged to completely identify the cardioprotective properties of ceftriaxone and MC-100093.

Exploring Ventilator-Associated Pneumonia: Microbial Clues and Biomarker Insights from a Retrospective Study.

Background and Objectives: Ventilator-associated pneumonia (VAP) is a common complication in critically ill patients receiving mechanical ventilation. The incidence rates of VAP vary, and it poses significant challenges due to microbial resistance and the potential for adverse outcomes. This study aims to explore the microbial profile of VAP and evaluate the utility of biomarkers and illness severity scores in predicting survival. Materials and Methods: A retrospective cohort study was conducted involving 130 patients diagnosed with VAP. Microbial analysis of bronchoalveolar lavage (BAL) fluid, as well as measurements of C-reactive protein (CRP) and procalcitonin (PCT) levels, were performed. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated to assess illness severity. Statistical analyses were conducted to determine correlations and associations. Results: The study revealed that Klebsiella pneumoniae (K. pneumoniae) (50.7%) and Pseudomonas aeruginosa (P. aeruginosa) (27.69%) were the most identified microorganisms in VAP cases. SOFA (p-value < 0.0001) and APACHE II (p-value < 0.0001) scores were effective in assessing the severity of illness and predicting mortality in VAP patients. Additionally, our investigation highlighted the prognostic potential of CRP levels (odds ratio [OR]: 0.980, 95% confidence interval [CI] 0.968 to 0.992, p = 0.001). Elevated levels of CRP were associated with reduced survival probabilities in VAP patients. Conclusion: This study highlights the microbial profile of VAP and the importance of biomarkers and illness severity scores in predicting survival. Conclusions: The findings emphasize the need for appropriate management strategies to combat microbial resistance and improve outcomes in VAP patients.

Oryza glumaepatula and calcium oxide nanoparticles enhanced Cr stress tolerance by maintaining antioxidant defense, chlorophyll and gene expression levels in rice.

Chromium (Cr), a potent heavy metal, threatens rice cultivation due to its escalating presence in soil from human activities. Wild rice contains useful genes for phytoremediation; however, it is difficult to use directly for metal mitigation. Here, a single segment substitution line (SSSL), SG001, was developed by crossing O. glumaepatula and Huajingxian74 (HJX) to evaluate the survival ability of plants against Cr. Further, we explored the potential effect of calcium oxide nanoparticles (CaO-NPs) (50 µM) to minimize the toxic effect of Cr (100 µM) in rice cultivars, SG001 and HJX. The findings of this study indicated that Cr toxicity led to increased oxidative stress. This was shown by higher levels of hydrogen peroxide (H2O2), which was increased by 104% in SG001 and 177% in HJX, and malondialdehyde (MDA) increased by 79% in SG001 and 135% in HJX. Furthermore, it also depicted that Cr toxicity considerably declined shoot and root length, shoot and root fresh weight by 30%, 27%, 25%, and 20% in SG001 and 44%, 51%, 42%, and 45% in HJX, respectively. This mitigation was evidenced by decreased Cr contents, increased calcium (Ca) levels in SG001, and the maintenance of chlorophyll, antioxidant defense, and gene expression levels. Moreover, there was a notable reduction in MDA and H2O2, while the defense mechanisms of key antioxidants, including ascorbate peroxidase, superoxide dismutase, glutathione, catalase, and peroxidase were upregulated, along with an increase in soluble protein contents in both rice cultivars after applying CaO-NPs. CaO-NPs effectively restored cellular and subcellular structural integrity and growth in both lines, which had been seriously disrupted by Cr toxicity. Overall, our findings suggest that SG001, in combination with CaO-NPs, could serve as an effective strategy to mitigate Cr toxicity in plants.

Monoterpenoid synergy: a new frontier in biological applications.

Monoterpenoids, compounds found in various organisms, have diverse applications in various industries. Their effectiveness is influenced by the oil's chemical composition, which in turn is influenced by plant genotype, environmental conditions, cultivation practices, and plant development stage. They are used in various industries due to their distinctive odor and taste, serving as ingredients, additives, insecticides, and repellents. These compounds have synergistic properties, resulting in superior combined effects over discrete ones, potentially beneficial for various health purposes. Many experimental studies have investigated their interactions with other ingredients and their antibacterial, insecticidal, antifungal, anticancer, anti-inflammatory, and antioxidant properties. This review discusses potential synergistic interactions between monoterpenoids and other compounds, their sources, and biological functions. It also emphasizes the urgent need for more research on their bioavailability and toxicity, underlining the importance and relevance of this comprehensive study in the current scientific landscape.