Characterization of Demographic, Clinical, and Laboratory Risk Factors for Stroke in a Tertiary Hospital in Riyadh, Saudi Arabia.

Background Stroke is a major cause of death and long-term disability worldwide, with varying incidence and risk factors across different populations. This study aims to analyze demographic, clinical, and laboratory risk factors for stroke among the Saudi Arabian population to enhance the understanding of its behavior and associated mortality. Methods In this retrospective cohort study, we analyzed data from 3586 patients diagnosed with hemorrhagic or non-hemorrhagic stroke at King Fahad Medical City from January 1, 2020, to November 11, 2022. We collected data on demographic variables, past medical history, social history, nationality, and laboratory components. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 27.0. (Armonk, NY: IBM Corp.), with significance set at p<0.05. Results The study population was predominantly male (57.86%) and within the age group of 51 to 80 years (58.8%). A significant portion of patients were Saudi nationals (99.6%), with hypertension (50.2%) and diabetes (40.4%) being the most common comorbidities. Laboratory abnormalities related to sodium and potassium levels were strongly linked to mortality rates. Notably, ischemic stroke was the most common type across all age groups, except for patients under age 16, where hemorrhagic stroke was more prevalent. Conclusions Our findings reveal significant associations between stroke risk factors and mortality within the Saudi Arabian population, highlighting the impact of hypertension, diabetes, and electrolyte imbalances. The study underscores the need for targeted stroke prevention and management strategies in Saudi Arabia, aligning with global trends to mitigate the burden of this disease.

Healthcare Providers' knowledge, attitudes and practice in relation to drug hypersensitivity reactions at King Abdulaziz Medical City in Riyadh.

Background: Drug hypersensitivity reactions (DHRs) are immune-mediated responses triggered by exposure to a drug. DHRs are responsible for serious adverse drug reactions (ADRs) and are considered the fifth leading cause of death. This study aims to assess and evaluate the knowledge, practice, and attitudes of healthcare providers (HCPs) towards DHRs. Methods: A cross-sectional survey was conducted at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. Healthcare providers, including pharmacists, physicians, and nurses, were recruited using a convenience sampling method to complete the survey. The survey comprised three domains: knowledge (14 items), attitudes (5 items), and practices (6 items), utilizing a standardized self-administered questionnaire. Results: The survey was completed by 373 healthcare providers. The respondents were predominantly female (72.1 %) with a mean age of 33.8 ± 7.8 years. Of the respondents, 64 % were nurses, 25 % pharmacists, and 11.3 % physicians. Educational levels varied, with 53 % holding a bachelor's degree, 22 % an associate degree, and 25 % a master's degree or higher. The median knowledge score was 48. Female healthcare providers, those with advanced levels of education, and physicians had higher knowledge scores compared to male and nurse participants (p < 0.05). One-third of the respondents (33 %) were satisfied with their knowledge of DHRs, and 42 % believed HCPs should receive more advanced training in DHR management. Less than a quarter of HCPs reported inquiring about patients' histories of hypersensitivity reactions. Conclusions: The study revealed that healthcare workers had a relatively low level of knowledge about drug hypersensitivity reactions and lacked a consensus on DHR management. While displaying a positive attitude towards DHRs, they often did not translate this attitude into consistent clinical practice.

Exploring the Enigmatic Link: Unraveling the Relationship Between Obesity and Cigarette Smoking Among Diverse College Students at Imam Mohammed Ibn Saud Islamic University in Riyadh, Saudi Arabia.

BACKGROUND: Obesity is defined as an excess of body fat. This medical condition frequently results in a high BMI and an increased risk of a variety of health problems, including diabetes, cardiovascular disease, and certain types of cancer. Cigarette smoking includes inhaling smoke created by the combustion of tobacco. It is linked to a variety of health issues, including lung cancer, heart disease, and respiratory ailments, and is a primary cause of preventable disease and premature death worldwide. The association between obesity and cigarette smoking is complex and incompletely understood. This study aims to investigate the intriguing association between obesity and cigarette smoking among diverse college students at Imam Mohammed Ibn Saud Islamic University in Riyadh, Saudi Arabia. METHODOLOGY: The study was conducted as an observational study, specifically an analytical cross-sectional study, to measure the prevalence of cigarette smoking and obesity and their association. This type of study is chosen because of its advantages including targeting a large sample in a short time and inexpensive way, with no loss to follow-up, unlike some other study designs. RESULTS: In this study, we were able to collect data from 603 participants, of which 57.4% were male and 67.8% of them aged between 20 and 24 years old. Moreover, we found that 39.6% had normal weight; however, the prevalence of obesity, overweight, and underweight were 24%, 28.1%, and 8.3%, respectively. Considering the prevalence of smoking, we found that 22.6% of the participants reported being current smokers, while 5.3% were former smokers. There is a significant difference between participants with different BMIs (P=0.001). The prevalence of smoking was significantly higher in obese and overweighted participants (35.1% and 31.3%, respectively) compared with 28.4% in normal-weighted participants. CONCLUSION: The prevalence of smoking and obesity in this study was significantly higher than reported in different studies. Moreover, we found a significant relationship between smoking and obesity; however, further investigation should be conducted to determine the cause of this relationship.

Genetic variants associated with dengue hemorrhagic fever. A systematic review and meta-analysis.

Dengue hemorrhagic fever (DHF) is a severe condition resulting from the dengue virus, with four serotypes known as DEN-1, DEN-2, DEN-3, and DEN-4. Genetic variations play a crucial role in influencing susceptibility to DHF. Therefore, this investigation conducted a meta-analysis to uncover genetic changes that might have remained undetected in individual studies due to small sample sizes or methodological differences. Among 2212 initially identified studies, 23 were deemed suitable for analysis based on PRISMA guidelines. Toll-like receptors (TLR) and CD209 showed significant association with DHF (odds ratios: TLR=0.56, CD209 =0.55), indicating protective effects. However, tumor necrosis factor (TNF) and human leukocyte antigen (HLA) did not exhibit a statistically significant relationship with DHF. This study emphasizes the relevance of TLR and CD209 in DHF susceptibility and resistance across diverse geographical locations.

The effect of inhibiting hindbrain A2 noradrenergic neurons by 6-Hydroxydopamine on lipopolysaccharide-treated male rats autistic animal model.

Autism spectrum disorder (ASD) is a complex neurodevelopmental illness that often emerges in early childhood. The incidence of ASD has shown a notable rise in recent years. ASD is defined by deficits in social communication, and presence of rigid and repetitive behaviors and interests. The underlying mechanisms of ASD remain elusive. Multiple studies have documented the presence of neuroinflammation and increased levels of inflammatory cytokines, specifically, IL-6, TNF, and NF-κB, in various brain regions, including the prefrontal cortex (PFC) and hippocampus in individuals with ASD. Noradrenergic neurons play a crucial role in brain development and the regulation of motor, behavioral, and memory functions. This study sought to examine the impact of intracerebroventricular (icv.) injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), in the caudal dorsal vagal complex A2 neurons on various neuroinflammatory pathways at the hippocampus and PFC in valproic acid (VPA) autistic animal model. This was done in conjunction with an intraperitoneal (i.p.) injection of Lipopolysaccharides (LPS) in animal models with VPA-induced autism. We specifically examined the impact of the caudal fourth ventricle 6-OHDA icv. injection and LPS (i.p.) injection on self-grooming behavior. We measured the mRNA expression of IL-6, TNF-a, and NF-κB using qRT-PCR, and the protein expression of COX-2, GPX-1, p-AMPK, and AMPK using western blot analysis. The self-grooming activity was considerably higher in the combined treatment group (6-OHDA icv. + LPS i.p.) compared to the control group. A substantial increase observed in the expression of IL-6, TNF-α, and NF-κB genes in the PFC of the treatment group that received icv. Administration of 6-OHDA, compared to the control group. The VPA-autism rats that received the combo treatment exhibited a slight increase in the expression level of NF-κB gene in the hippocampus, compared to the control group. At the PFC, we noticed a substantial drop in the expression of the antioxidant protein GPX-1 in the group that received the combo treatment compared to the control group. Our data investigates a novel aspect that the 6-OHDA-induced inhibition of hindbrain A2 neurons could be influencing the neuroinflammatory pathways in the PFC and hippocampus of autistic animal models.

Cobalt-modulated dual emission carbon dots for ratiometric fluorescent vancomycin detection.

This work presents a simple yet selective fluorometric protocol for the quantification of vancomycin, an important antibiotic for treating infections caused by Gram-positive bacteria. A novel ratiometric fluorometric method for the determination of vancomycin is developed based on dual emissive carbon dots (DECDs) with emission at 382 nm and 570 nm in combination with Co2+ ions. Upon addition of Co2+ions, the fluorescence at 382 nm of DECDs is enhanced while emission at 570 nm remains constant. In the presence of vancomycin, it complexes with Co2+ leading to quenching of the 382 nm fluorescence due to strong binding with Co2+ in the Co@DECDs system. The DECDs are fully characterized by TEM and different spectroscopic techniques. The proposed ratiometric method is based on measuring fluorescence ratio (F570/F382) against vancomycin concentration and the method exhibits a good linearity range from 0.0 to 120.0 ng mL-1 with a low limit of detection (S/N = 3) of 0.31 ng mL-1. The method shows good selectivity with minimal interference from potential interfering species. This ratiometric fluorometric approach provides a promising tool for sensitive and specific vancomycin detection in clinical applications.

Selective fluorescence turn-on detection of combination cisplatin-etoposide chemotherapy based on N-CDs/GSH-CuNCs nanoprobe.

Cisplatin (CIS) and etoposide (ETP) combination therapy is highly effective for treating various cancers. However, the potential for pharmacokinetic interactions between these drugs necessitates selective sensing methods to quantitate both CIS and ETP levels in patient's plasma. This work develops a dual fluorescence probe strategy using glutathione-capped copper nanoclusters (GSH-CuNCs) and nitrogen-doped carbon dots (N-CDs) for the simultaneous analysis of CIS and ETP. The fluorescence signal of GSH-CuNCs at 615 nm increased linearly with CIS concentration while the N-CD emission at 480 nm remained unaffected. Conversely, the N-CD fluorescence was selectively enhanced by ETP with no interference with the CuNC fluorescence. Extensive materials characterization including UV-vis, fluorescence spectroscopy, XRD, and TEM confirmed the synthesis of the nanoprobes. The sensor showed high sensitivity with limits of detection of 6.95 ng mL-1 for CIS and 7.63 ng mL-1 for ETP along with excellent selectivity against potential interferences in rabbit plasma. Method feasibility was demonstrated with application to real rabbit plasma samples. The method was further applied to estimate the pharmacokinetic parameters of CIS before and after ETP coadministration. The dual nanoprobe sensing strategy enables rapid and selective quantitation of CIS and ETP levels to facilitate therapeutic drug monitoring and optimization of combination chemotherapy regimens.

Worsening of imiquimod-induced psoriasiform inflammation in mice by environmental pollutant, di-(2-ethylhexyl) phthalate through dysregulation in IL-17A and Nrf2/iNOS signaling in peripheral myeloid and CD4 + T cells.

Psoriasis is a devastating autoimmune illness resulting from excessive keratinocyte growth and leukocyte infiltration into the dermis/epidermis. In the pathogenesis of psoriasis, different immune cells such as myeloid cells and CD4 + T cells play a key role. Th17/Th1 immune responses and oxidant-antioxidant responses are critical in regulation of psoriatic inflammation. Di-2-ethylhexyl phthalate (DEHP) is one of the well-known plasticizers and has widespread use worldwide. DEHP exposure through ingestion may produce harmful effects on the skin through systemic inflammation and oxidative stress, which may modify psoriatic inflammation. However, the effect of oral DEHP exposure on inflammatory cytokines and Nrf2/iNOS signaling in myeloid cells and CD4 + T cells in the context of psoriatic inflammation has not been investigated earlier. Therefore, this study explored the effect of DEHP on systemic inflammation in myeloid cells (IL-6, IL-17A, IL-23), Th17 (p-STAT3, IL-17A, IL-23R, TNF-α), Th1 (IFN-γ), Treg (Foxp3, IL-10), and Nrf2/iNOS signaling in imiquimod (IMQ)-induced mouse model of psoriasis-like inflammation. Our study showed increased Th17 signaling in imiquimod model which was further aggravated by DEHP exposure. Further, Nrf2 and iNOS signaling were also elevated in IMQ model where DEHP exposure further increased iNOS expression but did not modify the Nrf2 expression. Most importantly, IL-17A levels were also elevated in myeloid cells along with IL-6 which were further elevated by DEHP exposure. Overall, this study shows that IL-17A signaling is upregulated, whereas there is deficiency of Nrf2/HO-1 signaling by DEHP exposure in mice with psoriasiform inflammation. These observations suggest that DEHP aggravates IL-17A-mediated signaling both in CD4 + T cells as well as myeloid cells which is linked to exacerbation of IMQ-induced psoriatic inflammation in mice. Strategies that counteract the effect of DEHP exposure in the context of psoriatic inflammation through downregulation of IL-17A may be fruitful.

The Cross Talk Between Psoriasis, Obesity, and Dyslipidemia: A Meta-Analysis.

Although psoriasis is a multi-organ disease, it is usually managed as a skin disease, ignoring its associated serious comorbidities. This meta-analysis aimed to investigate the relationship between psoriasis, dyslipidemia, and obesity. Two authors independently searched three databases (PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), The Cochrane Library, and Google Scholar). The search was set for articles published in the English language during the period from January 2013 to August 2023. The keywords "psoriasis", "hypercholesterolemia", "dyslipidemia", "low-density lipoproteins", "high body mass index", and "obesity", were used. Out of the 145 full texts reviewed, only seven studies fulfilled the inclusion and exclusion criteria (773,761 participants and 196,593 events). Psoriasis was associated with dyslipidemia and obesity (odds ratio (OR)=1.63, 95% CI: 1.42-1.88 and OR=1.70, 95% CI: 1.43-2.02), respectively, with significant heterogeneity (98% and 97%, respectively). Dyslipidemia and obesity were significant psoriasis comorbidities; a broader approach, viewing psoriasis as a multi-organ disease, is recommended for optimal treatment and outcomes.

The Association of Psoriasis, Diabetes Mellitus, and Hypertension: A Meta-Analysis.

Psoriasis is a systemic disease affecting various organs; however, it is usually thought of as a skin disease. A multidisciplinary approach is needed for better outcomes. The current meta-analysis assessed the association between diabetes mellitus, high blood pressure, and psoriasis. We searched four databases, including Cochrane Library, PubMed, MEDLINE, and Google Scholar, for relevant articles using the following keywords: psoriasis, hypertension, high blood pressure, cardiovascular risk factors, and diabetes mellitus. The author's name, year, and country of publication, diabetes, and hypertension among patients with psoriasis and control subjects were collected and entered into a Microsoft Excel sheet. Out of 1209 articles retrieved, 903 articles remained after duplication removal. From the 82 full texts screened, only seven studies fulfilled the inclusion and exclusion criteria. Psoriasis was associated with diabetes and hypertension: odds ratio 1.38, 95% CI 1.17-1.64; P-value 0.0002, chi-square 224.93, and odds ratio 1.60, 95% CI 1.41-1.81, P-value 0.00001, chi-square 226.59, respectively. Substantial heterogeneity was observed (I2 for heterogeneity, 97%, P < 0.001). A broad approach is needed to address the associated comorbidities and select the appropriate therapeutic approach. Randomized controlled trials investigating the best drugs for the treatment of psoriasis and its associated cardiovascular risk factors are needed.

Examining the Effects of Dasatinib, Sorafenib, and Nilotinib on Vascular Smooth Muscle Cells: Insights into Proliferation, Migration, and Gene Expression Dynamics.

BACKGROUND: Dasatinib, nilotinib, and sorafenib are clinically proven tyrosine kinase inhibitors (TKIs) used for the treatment of leukemia and hepatocellular carcinoma. However, there is a growing concern regarding cardiotoxicity associated with their use. The impact of these TKIs on vascular smooth muscle cells (VSMCs) remains unexplored. This study aims to investigate the effects of TKIs on VSMC proliferation and migration, as well as to elucidate the underlying mechanisms involving inflammatory and apoptotic pathways. METHODS: VSMCs were extracted from albino rats and cultured in vitro. The cells were divided into four experimental groups: control, dasatinib, sorafenib, and nilotinib. The MTT assay was employed to assess the cytotoxic effects of TKIs on VSMCs. A scratch assay was conducted to evaluate the inhibitory potential of TKIs on VSMC migration. Flow cytometry analysis was used to detect apoptotic cells. Real-Time PCR expression was utilized to determine the differential gene expression of apoptotic and inflammatory markers. RESULTS: Dasatinib, nilotinib, and sorafenib demonstrated significant inhibitory effects on VSMC viability and migration at low concentrations (<1 µmol/L, p < 0.05). Furthermore, gene expression analysis revealed up-regulation of inflammatory biomarkers (TNF-α, IL-6, and IL-1ß) and apoptotic markers (P53, BAX), along with down-regulation of the anti-apoptotic biomarker BCL-2 in response to all TKIs. CONCLUSIONS: This study demonstrates that dasatinib, nilotinib, and sorafenib inhibit VSMC proliferation and migration, suggesting their potential to induce vascular injury and remodeling by activating inflammation and apoptosis pathways. These findings highlight the need for further investigation into the cardiotoxic effects of these TKIs and the development of strategies to mitigate their adverse vascular effects.

A novel microextraction technique aided by air agitation using a natural hydrophobic deep eutectic solvent for the extraction of fluvastatin and empagliflozin from plasma samples: application to pharmacokinetic and drug-drug interaction study.

This study focuses on the interaction between the antihyperlipidemic drug fluvastatin (FLV) and the antidiabetic drug empagliflozin (EMP), which are commonly co-administered medications. EMP's impact on FLV levels is attributed to its inhibition of organic anion transporting polypeptide 1B1 (OATP1B1), responsible for FLV liver uptake, consequently elevating FLV concentrations in blood. Traditional extraction methods for FLV faced difficulties due to its high hydrophobicity. In this study, a hydrophobic natural deep eutectic solvent (NDES) using air assisted dispersive liquid-liquid microextraction (AA-DLLME) was utilized as an excellent choice for achieving the highest extraction recovery, reaching 96% for FLV and 92% for EMP. The NDES was created through the combination of menthol and hippuric acid in a 4 : 1 ratio, making it a green and cost-effective pathway. Liquid phase microextraction followed by spectrofluorometric measurements of FLV at λem = 395 nm and EMP at λem = 303 nm, with excitation at a single wavelength of 275 nm was carried out. Response surface methodology (RSM) relying on central composite design (CCD) was used to optimize the variables affecting the AA-NDES-DLLME. The optimized conditions for extraction are: NDES volume of 200 µL, centrifugation time of 15 minutes, air-agitation cycle of 6 cycles, and sample pH of 4.0. Under these optimized conditions, the developed method exhibited good linearity and precision. The method showed good recoveries from rabbit plasma samples spiked at varying concentrations of the analyzed compounds. To assess the applicability and effectiveness of the hydrophobic DES, the validated method was applied to extract the studied drugs from rabbit plasma samples after oral administration of FLV alone and in combination with EMP. The pharmacokinetic parameters of FLV were calculated in both cases to investigate any changes and determine the need for dose adjustment.

A selective dual quenching sensor (EY/BG@CDs) for simultaneous monitoring of gentamicin and ketorolac levels in plasma: a highly efficient platform that caters to the needs of therapeutic drug monitoring.

This research work introduces a novel sensor that utilizes two fluorophores to enable simultaneous monitoring of gentamicin sulphate (GNT) and ketorolac tromethamine (KET). The innovative sensor is composed of carbon dots (CDs) derived from black grapes (BG) and eosin Y (EY) dye. The interaction between the studied drugs and EY/BG@CDs sensor components allows for their simultaneous detection where GNT quenches the fluorescence of EY at 535 nm without affecting the fluorescence of CDs, while KET quenches the fluorescence of BG@CDs at 385 nm without impacting EY fluorescence. The BG@CDs probe was successfully characterized using various techniques such as absorption spectrophotometry, spectrofluorimetry, TEM imaging, infrared spectroscopic analysis, and XRD analysis. The suggested methodology was observed to be highly sensitive for the simultaneous determination of GNT and KET in their spiked rabbit plasma samples, with wide linear ranges and low limit of detection (LOD) values. The studied drugs were extracted using a highly selective extraction method involving protein precipitation followed by mixed mode solid phase extraction using an Oasis WCX cartridge. The simultaneous determination of GNT and KET is essential due to the potential interactions between the studied drugs. Therefore, this analysis can be used to evaluate the necessity of dose monitoring and the potential adverse effects of co-administration of these drugs.

Augmented antitumor effects of erlotinib and cabozantinib on A549 non-small cell lung cancer: In vitro and in vivo studies.

Non-small cell lung carcinoma is a challenging disease worldwide. This study aims to determine whether combining erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, with cabozantinib, a mesenchymal-epithelial transition factor (c-Met) inhibitor, would have an augmented therapeutic benefit on A549 cells. The combination of erlotinib and cabozantinib (5 µM) inhibited A549 cell viability compared to each monotherapy at ≥ 10 µM as confirmed by the MTT assay. Combination therapy also has a more potent inhibition of cellular migration than monotherapy using the wound-healing assay. Furthermore, mRNA expression analyses for assessing apoptosis, metastasis, and cell cycle-related genes, the results showed that combination therapy significantly inhibits levels of BCL-2, MMP-9, VEGF, and TGF-ß while inducing p53, p21, and BAX expression. In terms of oncogenic markers, western blotting analysis showed a significant reduction of BCl-2 expression and elevation in caspase3, p53, and p21 proteins as indicators of cell death via apoptosis. The antitumor in vivo effect of the combination therapy showed significant tumor inhibition compared to monotherapy. In conclusion, combination therapy could be a potential promising strategy to treat non-small cell lung carcinoma.

Protective role of Dodonaea viscosa extract against streptozotocin-induced hepatotoxicity and nephrotoxicity in rats.

Previous investigations have shown that D. viscosa herbal extract is often used to treat a variety of diseases. Therefore, the purpose of this study was to investigate any additional potential impacts on rat liver and kidney damage induced by diabetes. Streptozotocin (STZ) (60 mg/kg/day) was given as a single dosage to cause type 1 diabetes. After then, diabetic rats received oral doses of D. viscosa for four weeks at 150 and 300 mg/kg/day. Blood, liver, and kidney tissues were collected at the end of the treatment and examined. Analysis was made of the serum lipid profile, liver, and kidney functions, as well as blood biochemistry. Moreover, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), prostaglandin E-2 (PGE-2), and nitric oxide (NO) were estimated in serum. In liver and kidney samples, thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH), as well as the pro-inflammatory cytokines and enzymatic activities of glutathione peroxidase (GPx), glutathione reeducates (GR), glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were analyzed. Histological changes in liver and kidney cross-sections were also observed. Our findings demonstrated that D. viscosa dramatically decreased pro-inflammatory indicators in blood, kidney, and liver tissues as well as blood glucose, and restored insulin levels, and lipid profiles. Additionally, it significantly raises the antioxidant enzyme activity SOD, CAT, GPx, and GST, while significantly lowering TBARs levels. The above-mentioned biochemical changes that took place in tissues were further supported by histological alterations. These findings imply that D. viscosa protects against STZ-induced hyperglycemia, aberrant lipid synthesis, and oxidative stress and that these benefits may be mediated by interacting with various targets to increase the levels of antioxidant enzymes in the liver and kidneys. Its mode of action and safety for use as medicine against various metabolic problems caused by diabetes require more research.

The Potential Protective Role of Naringenin against Dasatinib-Induced Hepatotoxicity.

Dasatinib (DASA) is a novel tyrosine kinase inhibitor, approved for leukemia treatment. However, the long-term use of DASA induces several complications, especially liver damage. On the other hand, Naringenin (NGN) is a potent antioxidant and anti-inflammatory agent which is known to exert protective effects in several liver disease animal models. Yet, the effect of NGN on DASA-induced hepatotoxicity has not been examined. This study investigated the hepatoprotective effects of NGN against DASA-induced acute liver injury, using a mouse model. The mice were given NGN (50, 100, and 200 mg/kg po) or saline for 7 days, followed by DASA on the eighth day (25 mg/kg p.o.). DASA treatment alone was found to cause overexpression of proinflammatory cytokines, such as interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and malonyl aldehyde (MDA), whereas attenuation of antioxidant genes including superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx). Interestingly, a pretreatment with NGN + DASA resulted in minimizing the proinflammatory mediators and restoring the levels of antioxidant genes. In addition, there was evidence of necro-inflammatory changes in histopathological findings in the liver samples after DASA administration which remarkably reduced with NGN + DASA. Thus, this study revealed that NGN could minimize the hepatotoxicity induced by DASA by providing anti-inflammatory and antioxidant protection.

Hydroxychloroquine ameliorates dasatinib-induced liver injury via decrease in hepatic lymphocytes infiltration.

Dasatinib is an effective treatment for chronic myeloid leukemia. However, cases of idiosyncratic hepatotoxicity were reported. This study was conducted to investigate the chemopreventive effects of hydroxychloroquine against dasatinib-induced hepatotoxicity. Balb/c mice were randomly assigned into four groups; vehicle control (5% DMSO, i.p., n = 6), dasatinib (50 mg/kg; i.p., n = 6), hydroxychloroquine (10 mg/kg, i.p., n = 6), and hydroxychloroquine + dasatinib (10 mg/kg + 50 mg/kg; i.p., n = 6). Treatments were given once every 2 days for 14 days. Serum and histopathological assessments of liver architecture and fibrosis were performed using H&E, Masson's trichrome, and reticulin staining. The infiltration of lymphocytes was assessed using immunohistochemistry. The gene expression of antioxidant enzymes (CAT, SOD-2, GPX-1) was assessed using real-time quantitative PCR. Dasatinib showed a significant increase in liver injury biomarkers (AST and ALT) with higher lymphocytes infiltration (as indicated by CD3+, CD4+, CD8+, and CD20+ immunohistochemistry). Hepatic tissue of Dasatinib group exhibited significant downregulation in the gene expression of antioxidant enzymes (CAT, SOD-2, and GPX-1) compared to the control group. However, the combination of hydroxychloroquine with dasatinib showed a slight increase in AST and ALT. Also, hydroxychloroquine + dasatinib treated mice showed a significant reduction in lymphocytes infiltration as compared to dasatinib. The results showed that dasatinib induces an immune response leading to an increase in lymphocytes infiltration which promotes hepatocyte destruction and persistent liver injury. The results also suggest that hydroxychloroquine ameliorates dasatinib-induced hepatotoxicity via reduction in hepatic infiltration of T and B immune cells.

The Progress of Speech Recognition in Health Care: Surgery as an Example.

Artificial Intelligence (AI) is a computer system that simulates intelligent human behavior. The use of AI is rapidly shifting Healthcare. Speech recognition (SR) is a type of AI physicians use to operate Electronic Health records (EHR). This paper aims to demonstrate the technological advancements made thus far concerning speech recognition in health care and explore multiple scholarly studies to generate a wide-ranging and detailed assessment of its current progress. The effectiveness of speech recognition is the heart of this analysis. This review investigates published papers on the progress and effectiveness of speech recognition in Healthcare. Eight research papers exploring the progress and effectiveness of speech recognition in Healthcare were thoroughly reviewed. Articles were identified from Google Scholar, PubMed, and the World Wide Web. The five relevant papers generally discussed the progress and current effectiveness of SR in Healthcare, implementing SR in the EHR, adapting healthcare workers to SR and the problems they face, developing an intelligent healthcare system based on SR and using SR systems in other languages. Conclusion: This report demonstrates the technological improvements realized concerning SR in Healthcare. It proved that SR could be a tremendous help to providers if every medical and health institution continued to progress in using this technology.

Targeting Store-Operated Calcium Entry Regulates the Inflammation-Induced Proliferation and Migration of Breast Cancer Cells.

Persistent challenges complicating the treatment of breast cancer remain, despite some recent undeniable successes. Sufficient evidence currently exists demonstrating the crucial role of inflammation, characterized by the enhanced activation of Toll-like receptor 4 (TLR4) and the COX-2/PGE2 pathway, in the migration and proliferation of breast cancer cells. Interestingly, the store-operated calcium entry (SOCE) pathway was shown to be essential for the TLR4 activity and COX-2 expression in immune cells such as macrophages and microglia. However, whether SOCE influences inflammatory signaling and the inflammation-induced proliferation and migration of breast cancer cells is still unknown. Thus, the current study intended to delineate the role of SOCE in the TLR4-induced inflammation, migration, and proliferation of breast cancer cells. To this end, MDA-MB-231 breast cancer cells were treated with lipopolysaccharide (LPS) to activate TLR4, BTP2 to inhibit SOCE, and Thapsigargin to induce SOCE. Following these treatments, several experiments were conducted to evaluate the proliferation and migration rates of the MDA-MB-231 cells and the expression of several inflammatory and oncogenic genes, including COX-2, PGE2, IL-6, IL-8, and VEGF. Different techniques were used to achieve the aims of this study, including qRT-PCR, Western blotting, ELISA, MTT, and wound healing assays. This study shows that SOCE inhibition using BTP2 suppressed the LPS-induced migration and proliferation of breast cancer cells. Additionally, treatment with LPS caused approximately six- and three-fold increases in COX-2 mRNA and protein expression, respectively, compared to the controls. The LPS-induced elevations in the COX-2 mRNA and protein levels were suppressed by BTP2 to the control levels. In addition to its effect on COX-2, BTP2 also suppressed the LPS-induced productions of PGE2, IL-6, IL-8, and VEGF. Conversely, SOCE induction using Thapsigargin enhanced the LPS-induced inflammation, migration, and proliferation of breast cancer cells. Collectively, these results provide evidence for the potentially important role of SOCE in inflammation-induced breast cancer progression processes. Thus, we argue that the current study may provide novel targets for designing new therapeutic approaches for the treatment of breast cancer.

Special considerations and pitfalls for intracerebral bleeding followed COVID-19 case treated by ECMO.

COVID-19, or coronavirus infection, is an acute respiratory illness caused by the corona virus that can develop into a life-threatening form of ARDS. Extracorporeal membrane oxygenation (ECMO) is a highly effective treatment for life-threatening instances. One of the many complications associated with ECMO was bleeding. COVID patients are at risk for intracerebral bleeding due to several factors, including the drug's action on ACE2 receptors, leading to hypertension, as well as hypercoagulability, dysregulated immune response, DIC, and the use of anticoagulants.