The potential role of micro-RNA 125b-5p level in predicting outcome from thrombolytic therapy in patients with acute ischemic stroke.

Several studies highlighted a significant role of specific miRNA as diagnostic and prognostic biomarkers for acute ischemic stroke. The aim of this work was to study micro-RNA 125b-5p level in patients with acute ischemic stroke in relation to stroke etiology, risk factors, severity and outcome. This case-control study was conducted on 40 patients with acute ischemic stroke eligible for receiving rt-PA and 40 age and sex matched healthy controls, Patients were submitted to neurological and radiological assessment. Functional outcome after 3 months was assessed using the modified Rankin Scale (mRS). Plasma micro-RNA 125b-5p levels were measured for both patients and control groups by quantitative real time PCR. MiRNA-125b-5p was extracted from the plasma samples then Real-time quantitative reversed transcription PCR (RT-qPCR) analysis was done. To analyze miRNA-125b-5p expression in plasma, the ∆Cq value of miRNA-125b-5p was calculated by subtracting Cq of miRNA-125b-5p from the average Cq of MiRNA RNU6B. Stroke patients had significantly higher circulating micro-RNA 125b-5p levels in comparison to healthy controls (P value = 0.01). The circulating levels of micro-RNA 125b-5p were positively correlated with stroke severity assessed by National Institutes of Health Stroke Scale (NIHSS) and infarction size. Stroke patients with poor outcome had significantly higher circulating levels of micro-RNA 125b-5p in comparison to those with good outcome (P value ≤ 0.001). The circulating levels of micro-RNA 125b-5p were significantly higher in patients who developed complications after receiving rt-PA (P value ≤ 0.001). Logistic regression model revealed that each unit increase in micro-RNA125b-5p decreased the odds of good outcome by 0.095 (95% CI 0.016-0.58, P value = 0.011). Plasma micro-RNA 125b-5p is significantly elevated is ischemic stroke patients. It is positively correlated with stroke severity and strongly associated with poor outcome and complications after thrombolytic therapy.

Novel quinoline/thiazinan-4-one hybrids; design, synthesis, and molecular docking studies as potential anti-bacterial candidates against MRSA.

In an attempt to develop effective and safe antibacterial agents, we synthesized novel thiazinanones by combining the quinolone scaffold and the 1,3-thiazinan-4-one group by reaction between ((4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)methylene)hydrazinecarbothioamides and 2,3-diphenylcycloprop-2-enone in refluxing ethanol in the presence of triethyl amine as a catalyst. The structure of the synthesized compounds was characterized by spectral data and elemental analysis, IR, MS, 1H and 13C NMR spectroscopy which showed two doublet signals for CH-5 and CH-6 and four sharp singlets for the protons of thiazinane NH, CH[double bond, length as m-dash]N, quinolone NH and OH, respectively. Also, the 13C NMR spectrum clearly showed the presence of two quaternary carbon atoms which were assigned to thiazinanone-C-5 and C-6. All the 1,3-thiazinan-4-one/quinolone hybrids were screened for antibacterial activity. Compounds 7a, 7e and 7g showed broad spectrum antibacterial activity against most of the tested strains either G +ve or G -ve. Compound 7e is the most potent antibacterial agent against MRSA with the minimum inhibitory concentration against MRSA found to be 48 µg mL-1 compared to the drug ciprofloxacin (96 µg mL-1). Additionally, a molecular docking study was performed to understand the molecular interaction and binding mode of the compounds on the active site of S. aureus Murb protein. In silico docking assisted data strongly correlated with the experimental approach of antibacterial activity against MRSA.

Our Experience in Using Lateral Chest Flap to Treat Axillary Hidradenitis Suppurativa.

Hidradenitis suppurativa is a chronic inflammatory condition that affects apocrine gland-bearing areas' causing abscesses and sinuses. Multimodality treatment is suggested for management. The surgical option is becoming more widely used, especially in drug-resistant cases. In this article, we describe a series of bilateral axillary hidradenitis cases which we treated with wide local excision and immediate reconstruction with lateral chest flap. Methods: Fourteen patients presented to our clinic with bilateral hidradenitis suppurativa of the axilla. The cases were all resistant to medical treatment. They were managed by excision and simultaneous reconstruction with lateral chest flaps. Results: At 3 months postoperatively, all patients had full shoulder range of motion and were completely satisfied with the aesthetic outcome, except for one patient who complained of the bulky look of his axilla. Liposuction was performed for him' with a pleasant resultant outcome. Conclusions: Our patients underwent wide local excision of bilateral disease plus reconstruction with lateral chest flaps in the same session. Our aim was to introduce a treatment option for moderate to severe axillary hidradenitis suppurativa that offers good aesthetic and functional outcomes.

Heterocycles from cyclopropenones.

Great attention has been paid to cyclopropenones as they are present in many natural sources. Various synthesized cyclopropenone derivatives also show a wide range of biological activities. The cyclopropenone derivatives undergo a variety of reactions such as ring-opening reactions, isomerization reactions, C-C coupling reactions, C-H activation, cycloaddition reactions, thermal and photo-irradiation reactions, and acid-base-catalyzed reactions under the influence of various chemical reagents (electrophiles, nucleophiles, radicals, and organometallics) and external forces (heat and light). Many previous reviews have dealt with the chemistry and reactions of cyclopropenones. However and to the best of our knowledge, the utility of cyclopropenones in the synthesis of heterocycles has not been reported before. Therefore, it would be interesting to shed light on this new topic. The present review article provides, for the first time, a comprehensive compilation of synthetic methods for the synthesis of various heterocyclic ring systems, as a significant family in the field of organic chemistry.

Attractive study of the antimicrobial, antiviral, and cytotoxic activity of novel synthesized silver chromite nanocomposites.

Antibiotic resistance is a global problem. This is the reason why scientists search for alternative treatments. In this regard, seven novel silver chromite nanocomposites were synthesized and assayed to evaluate their antimicrobial, antiviral, and cytotoxic activity. Five bacterial species were used in this study: three Gram-positive (Bacillus subtilis, Micrococcus luteus, and Staphylococcus aureus) and two Gram-negative (Escherichia coli and Salmonella enterica). Three fungal species were also tested: Candida albicans, Aspergillus niger, and A. flavus. The MIC of the tested compounds was determined using the bifold serial dilution method. The tested compounds showed good antibacterial activity. Maximum antibacterial activity was attained in the case of 15 N [Cobalt Ferrite (0.3 CoFe2O4) + Silver chromite (0.7 Ag0.5Cr2.5O4)] against M. luteus. Concerning antifungal activity, C. albicans was the most susceptible fungal species. The maximum inhibition was recorded also in case of 15 N [Cobalt Ferrite (0.3 CoFe2O4) + Silver chromite (0.7 Ag0.5Cr2.5O4)]. The most promising antimicrobial compound 15 N [Cobalt Ferrite (0.3 CoFe2O4) + Silver chromite (0.7 Ag0.5Cr2.5O4)] was assayed for its antiviral and cytotoxic activity. The tested compound showed weak antiviral activity. The cytotoxic activity against Mammalian cells from African Green Monkey Kidney (Vero) cells was detected. The inhibitory effect against Hepatocellular carcinoma cells was detected using a MTT assay. The antimicrobial effect of the tested compounds depends on the tested microbial species. The tested compounds could be attractive and alternative antibacterial compounds that open a new path in chemotherapy.

Autoxidation of 4-Hydrazinylquinolin-2(1H)-one; Synthesis of Pyridazino[4,3-c:5,6-c']diquinoline-6,7(5H,8H)-diones.

An efficient synthesis of a series of pyridazino[4,3-c:5,6-c']diquinolines was achieved via the autoxidation of 4-hydrazinylquinolin-2(1H)-ones. IR, NMR (1H and 13C), mass spectral data, and elemental analysis were used to fit and elucidate the structures of the newly synthesized compounds. X-ray structure analysis and theoretical calculations unequivocally proved the formation of the structure. The possible mechanism for the reaction is also discussed.

Synthesis, Characterization, and In Vivo Study of Some Novel 3,4,5-Trimethoxybenzylidene-hydrazinecarbothioamides and Thiadiazoles as Anti-Apoptotic Caspase-3 Inhibitors.

The present study aims to discover novel derivatives as antiapoptotic agents and their protective effects against renal ischemia/reperfusion. Therefore, a series of new thiadiazole analogues 2a-g was designed and synthesized through cyclization of the corresponding opened hydrazinecarbothioamides 1a-g, followed by confirmation of the structure via spectroscopic tools (NMR, IR and mass spectra) and elemental analyses. The antiapoptotic activity showed alongside decreasing of tissue damage induced by I/R in the kidneys of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Most of the cyclized thiadiazoles are better antiapoptotic agents than their corresponding opened precursors. Particularly, compounds 2c and 2g were the most active antiapoptotic compounds with significant biomarkers. A preliminary mechanistic study was performed through caspase-3 inhibition. Compound 2c was selected along with its corresponding opened precursor 1c. An assay of cytochrome C revealed that there is an attenuation of cytochrome C level of about 5.5-fold, which was better than 1c with a level of 4.1-fold. In caspases-3, 8 and 9 assays, compound 2c showed more potency and selectivity toward caspase-3 and 9 compared with 1c. The renal histopathological investigation indicated normal renal tissue for most of the compounds, especially 2c and 2g, relative to the control. Finally, a molecular docking study was conducted at the caspase-3 active site to suggest possible binding modes.

Environmental, inflammatory, and anti-inflammatory squad in acne vulgaris pathogenesis: AhR, IL-36, and IL-38.

BACKGROUND: Acne vulgaris (AV) is an extraordinarily common skin condition. The high prevalence of AV is linked to the exposure factors, as environmental pollutants and climatic factors, occupational, psychosocial, and lifestyle factors. The AhR plays a critical part in environmental toxic action. The AhR expression and imbalance in the IL-36 & 38 expression may have a role in inflammation and AV pathogenesis. AIMS: To detect possible links between environmental, inflammatory, and anti-inflammatory factors in AV pathogenesis through measuring AhR, IL-36, and IL-38 mRNA gene expression levels. PATIENTS AND METHODS: Total of 100 subjects (70 AV patients and 30 apparently healthy control subjects) were tested for AhR, IL-36γ, and IL-38 mRNA levels by quantitative real-time PCR. RESULTS: The median levels of AhR and IL-36 mRNA gene expression were considerably greater, while that of IL-38 was essentially lower in AV than healthy subjects (p < 0.001, 0.021 and 0.002, respectively). The AhR and IL-36 mRNA gene expression levels increased, while IL-38 decreased significantly with higher grades of severity (p < 0.001, 0.001, and <0.001, respectively). ROC curve showed that AhR mRNA gene expression level had the best AUC for diagnosis of AV, with better sensitivity and specificity than IL-36 and IL-38. CONCLUSIONS: Higher levels of AhR, IL-36, and lower levels of IL-38 gene expression were significantly associated with AV patients and higher grades of severity. AhR had better diagnostic ability than IL-38 and IL-36.

Synthesis of 3,3'-methylenebis(4-hydroxyquinolin-2(1H)-ones) of prospective anti-COVID-19 drugs.

During formylation of 2-quinolones by DMF/Et3N mixture, the unexpected 3,3'-methylenebis(4-hydroxyquinolin-2(1H)-ones) were formed. The discussed mechanism was proved as due to the formation of 4-formyl-2-quinolone as intermediate. Reaction of the latter compound with the parent quinolone under the same reaction condition gave also the same product. The structure of the obtained products was elucidated via NMR, IR and mass spectra. X-ray structure analysis proved the anti-form of the obtained compounds, which were stabilized by the formation hydrogen bond. Molecular docking calculations showed that most of the synthesized compounds possessed good binding affinity to the SARS-CoV-2 main protease (Mpro) in comparable to Darunavir.

Evaluation of serum level of omentin-1 in females with hirsutism.

BACKGROUND: Hirsutism is a common clinical condition encountered in day-to-day practice. The androgenic causes account for more than 80% of these patients and include polycystic ovary syndrome (PCOS), which affects about 70%-80% of hirsute women. The second most common cause is idiopathic hirsutism. Omentin-1 is an adipokine mainly produced by visceral adipose tissue. AIM: The current study aimed at evaluating omentin-1 levels in hirsute females with PCOS and in idiopathic hirsutism. PATIENTS AND METHODS: Eighty-five females were included in this study. They were classified into three groups: thirty hirsute patients with PCOS, thirty females with idiopathic hirsutism, and twenty-five healthy control females. The participants were subjected to history taking, physical and dermatological examination. A gynecological history and radiological examination of the ovary also were done. Serum testosterone and omentin-1 were measured by ELISA. RESULTS: Serum testosterone was statistically elevated in PCOS than other groups. Serum omentin-1 in females with idiopathic hirsutism was statistically significantly higher than control and PCOS. There was a significant inverse correlation between serum testosterone level and serum omentin-1 level. CONCLUSION: Omentin-1 may be involved in the pathogenic process of hirsutism.

Detection of CD34/CXCR4+ stem cells in peripheral blood of patients following acute myocardial infarction.

Bone marrow harbors a population of tissue-committed stem cells that are CD34+/CXCR4+. These potential cardiac progenitors which express cardiac and endothelial markers may contribute to cardiac regeneration. The ability of injured myocardium to recruit extracardiac stem cells after injury would be beneficial to aid in myocardial repair and regeneration. The aim of this study was to answer the question whether acute myocardial infarction (AMI) related stress may trigger the increase of CD34/CXCR4+ stem cells number in peripheral blood in response to myocardial ischemic injury which might be accompanied with increased release of this population of stem cells in peripheral blood as well as to correlate this phenomenon with other clinical and laboratory parameters such as diabetes, chest pain, smoking, streptokinase administration and elevated cardiac enzymes. The study was conducted on 25 newly diagnosed AMI patients who attended the emergency department of National Heart Institute. They were compared to a control group of 25 apparently healthy sex and age matched individuals. The percentage of CD34+ cells as well as percentage of cells coexpressing CD34/CXCR4+ and their expression intensity were assessed by Flowcytometery. These parameters were correlated to other laboratory and clinical data. The absolute CD34+ as well as the CD34/CXCR4+ cell counts were significantly higher in patients upon admission in comparison to control group (P < 0.01). While CD34 expression was significantly higher in patients compared to control group, CXCR4 expression on CD34+ cells was significantly lower in patients than control group (P < 0.05). Diabetes, duration of chest pain and streptokinase administration had no significant effect on CD34/CXCR4+ number or the expression intensity of both markers (p > 0.05). Otherwise, CXCR4 intensity was lower in non-smoker than smoker patients (P < 0.05). Patients admitted with normal cardiac enzymes, including Creatine Kinase (CK) and Creatine Kinase MB fraction (CK-MB) activity, showed no significant difference in CD34/CXCR4+ number or the expression intensity of CD34 marker in comparison to those admitted with high levels of enzymes (P > 0.05). However, the expression intensity of CXCR4 was significantly low in patients admitted with elevated cardiac enzymes (P < 0.05). In conclusion, there is a pool of CD34/CXCR4+ stem cells circulating in large number in peripheral blood of AMI patients post infarction together with low CXCR4 expression on these cells which are likely to contribute to myocardial repair following the acute ischemic injury.

Oxidative stress and platelet activation: markers of myocardial infarction in type 2 diabetes mellitus.

We compared lipids, lipid peroxidation product malondialdehyde (MDA), the acute phase reactant high-sensitivity C-reactive protein (hsCRP), interleukin 1beta (IL-1beta), and platelet selectin (P-selectin) between healthy controls, type 2 diabetes mellitus (DM) participants without myocardial infarction (MI), as well as type 2 DM participants with MI. Malondialdehyde, IL-1beta, and P-selectin levels were significantly higher in the diabetic participants with MI than in either healthy controls or diabetic participants without MI. In the diabetic groups, fasting blood glucose (FBG) level, glycated hemoglobin (HbA(1c)), MDA, hsCRP, and P-selectin were all significantly positively correlated with each other. This study suggests that increased levels of oxidative stress markers, proinflammatory markers, and adhesion molecules contribute to the atherosclerotic process that eventually leads to coronary artery disease in diabetic patients.