Hepatic Injury in COVID-19 Patients

لقد أثبتت الدراسات العملية بالفعل أن الفحوصات المخبرية للكبد مفيدة للغاية في تقييم وعلاج مرضى القصور الكبدي. لقد وجد أن بعض الإنزيمات والمنتجات النهائية للمسار الأيضي مثل مصل البيليروبين ، ألانين أمينو ترانسفيراز، أسبارتات أمينو ترانسفيراز ، نسبة الأمينو ترانسفيراز ، الفوسفاتيز القلوي ، جاما جلوتاميل ترانسفيراز ، 5 'نيوكليوتيداز، سيرولوبلازمين التي تعتبر حساسة للغاية لحدوث الشذوذ و يمكن اعتبارها علامة كيميائية حيوية بارزة لخلل في وظائف الكبد. كما لوحظ بشكل واضح أن فيروس كورونا المستجد المتلازمة التنفسية الحادة الوخيمة Corona Virus-2 (SARS-CoV-2) قد أدى في الغالب إلى متلازمة الضائقة التنفسية ، ولكن في نفس الوقت تم توثيق إصابة الكبد أيضًا. في واقع الأمر ، فإن آلية إصابة الكبد محدودة وغير مفهومة بشكل جيد ، لذلك قد تكون الإصابة الكبدية نتيجة استجابة التهابية جهازية ، أو عدوى فيروسية لخلايا الكبد ، أو ناتجة عن علاج العناية المركزة أو الأدوية. تسمم . مستقبلات الإنزيم المحول للأنجيوتنسين 2 (ACE2) ، والتي يتم توزيعها على نطاق واسع في الخلايا السنخية من النوع 2 ، هي المسار المقترح لمدخل الفيروس. من المثير للاهتمام أن نلاحظ أن مستقبلات الإنزيم المحول للأنجيوتنسين 2 توجد في خلايا الكبد الصفراوية وبطانة الأوعية الدموية والجهاز الهضمي. كما لوحظت صور نسيجية متوافقة مع التغيرات الوعائية ، والتي تتميز بزيادة عدد فروع الوريد البابي المرتبطة بالتوسع الهائل في التجويف، والتخثر اللمعي الجزئي أو الكامل للأوعية البابية والجيوب الأنفية ، وتليف السبيل البابي ، والتضخم بشكل ملحوظ والتليف.The practical studies have already proved that  the laboratory liver tests are  highly  useful in the evaluation and treatment of patients with hepatic dysfunction. It has been found that  some of the enzymes and the end products of the metabolic pathway such as serum bilirubin, alanine amino transferase, aspartate amino transferase, ratio of aminotransferases, alkaline phosphatase, gamma glutamyl transferase, 5’ nucleotidase, ceruloplasmin  that  are very sensitive for the abnormality occurred  may be considered as an outstanding  biochemical marker of liver dysfunction. It is noticed that  the novel coronavirus Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) infection mostly leads to respiratory distress syndrome, at the same time  liver injury is also documented. As a matter of fact, the mechanism of liver injury is limited and poorly understood. Therefore, the hepatic injury  might be due to a consequence of systemic inflammatory response, viral infection of hepatocytes, or  it comes as a result of intensive care treatment or drug toxicity. The host angiotensin-converting enzyme 2 (ACE2) receptors, which are widely distributed in type 2 alveolar cells, are the proposed route of viral entrance. It is interesting to note that ACE2 receptors are found in the liver's cholangiocytes, vascular endothelium, and gastrointestinal tract.            Histological pictures compatible with vascular alterations are observed, characterized by  the increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic

In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations

Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC50 = 51.8 and 40.1 μg/mL, respectively), which is relatively the same effect as 5-FU at CC50 = 69.4 μM and melphalan at CC50 = 36.3 μM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 μg/mL) exerted morphological changes and induced subG1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D (18) and O (12), and the flavonoid kaempferol (11). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera’s potential as an affordable source of therapeutic agents for a range of oral malignancies

Impact of adiponectin and oxidized low-density lipoprotein in acute coronary syndrome

Objectives This study aimed to investigate and measure the relationships between the adiponectin levels and oxidized-low density lipoprotein (Ox-LDL) in acute coronary syndrome (ACS) patients in holy Kerbala city, Iraq. Methods Fifty-eight patients included in the study. Patients admitted with a diagnosis of ACS and 30 control subjects. Circulating adiponectin and Ox-LDL were assessed; using enzyme-linked immunosorbent assays (ELISA). Results Adiponectin serum concentrations were signifcantly lower (p < 0.001) in subjects with ACS compared with control subjects. Ox-LDL serum concentrations were signifcantly higher (p < 0.001) in subjects with ACS compared with controls subjects. The ACS patients showed a signifcantly higher (p < 0.001) result in total cholesterol and signifcantly lower (p < 0.001) level in HDL-C. Conclusion Serum adiponectin negatively correlated with Ox-LDL level in patient group ACS and the healthy control group

Human Lung Cancer (A549) Cell Line Cytotoxicity and Anti-Leishmania major Activity of Carissa macrocarpa Leaves: A Study Supported by UPLC-ESI-MS/MS Metabolites Profiling and Molecular Docking

Lung cancer and cutaneous leishmaniasis are critical diseases with a relatively higher incidence in developing countries. In this research, the activity of Carissa macrocarpa leaf hydromethanolic extract and its solvent-fractions (n-hexane, EtOAc, n-butanol, and MeOH) against the lung adenocarcinoma cell line (A549) and Leishmania major was investigated. The MeOH fraction exhibited higher cytotoxic activity (IC50 1.57 &plusmn; 0.04 &mu;g/mL) than the standard drug, etoposide (IC50 50.8 &plusmn; 3.16 &mu;g/mL). The anti-L. major results revealed strong growth inhibitory effects of the EtOAc fraction against L. major promastigotes (IC50 27.52 &plusmn; 0.7 &mu;g/mL) and axenic amastigotes (29.33 &plusmn; 4.86% growth inhibition at 100 &mu;g/mL), while the butanol fraction exerted moderate activity against promastigotes (IC50 73.17 &plusmn; 1.62), as compared with miltefosine against promastigotes (IC50 6.39 &plusmn; 0.29 &mu;g/mL) and sodium stibogluconate against axenic amastigotes (IC50 22.45 &plusmn; 2.22 &mu;g/mL). A total of 102 compounds were tentatively identified using UPLC-ESI-MS/MS analysis of the total extract and its fractions. The MeOH fraction was found to contain several flavonoids and flavan-3-ol derivatives with known cytotoxic properties, whereas the EtOAc fractions contained triterpene, hydroxycinnamoyl, sterol, and flavanol derivatives with known antileishmanial activity. Molecular docking of various polyphenolics of the MeOH fraction with HDAC6 and PDK3 enzymes demonstrates high binding affinity of the epicatechin 3-O-&beta;-D-glucopyranoside and catechin-7-O-&beta;-D-glucopyranoside toward HDAC6, and procyanidin C2, procyanidin B5 toward PDK3. These results are promising and encourage the pursuit of preclinical research using C. macrocarpa&rsquo;s MeOH fraction as anti-lung cancer and the EtOAc fraction as an anti-L. major drug candidates

Impact of the International Nosocomial Infection Control Consortium (INICC)’s multidimensional approach on rates of ventilator-associated pneumonia in intensive care units in 22 hospitals of 14 cities of the Kingdom of Saudi Arabia

To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Approach (IMA) and use of INICC Surveillance Online System (ISOS) on ventilator-associated pneumonia (VAP) rates in Saudi Arabia from September 2013 to February 2017. A multicenter, prospective, before–after surveillance study on 14,961 patients in 37 intensive care units (ICUs) of 22 hospitals. During baseline, we performed outcome surveillance of VAP applying the definitions of the CDC/NHSN. During intervention, we implemented the IMA and the ISOS, which included: (1) a bundle of infection prevention practice interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback on VAP rates and consequences and (6) performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using generalized linear mixed models to estimate the effect of intervention. The baseline rate of 7.84 VAPs per 1000 mechanical-ventilator (MV)-days―with 20,927 MV-days and 164 VAPs―, was reduced to 4.74 VAPs per 1000 MV-days―with 118,929 MV-days and 771 VAPs―, accounting for a 39% rate reduction (IDR 0.61; 95% CI 0.5–0.7; P 0.001). Implementing the IMA was associated with significant reductions in VAP rates in ICUs of Saudi Arabia