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Acute renal failure (ARF) was induced by glycerol or paracetamol in experimental rats to evaluate the curative effects of gum Arabic and Boswellia sp. through different blood biochemical assays and hematological analyses. Results revealed presence of significant (P<0.05) increases in the levels of urea, creatinine, potassium (K+), sodium (Na+), chloride (Cl-) and blood acidity (H+), and significant (P<0.05) decreases in the levels of calcium (Ca+2) and bicarbonate (HCO3 -) in the rats treated only with glycerol or paracetamol in the positive control groups compared to the negative control group. These results indicated that glycerol or paracetamol caused ARF in these groups of rats whereas the blood analyses illustrated ARF symptoms such as increasing of urea and creatinine, hyperkalemia, hypocalcemia, hypoglycemia, blood acidosis and anemia occurring in the positive control groups. The blood analyses also illustrated recovery of these symptoms in the treated rats with gum Arabic and Boswellia sp. in drinking water (10% w/v) for 30 days. This indicated the curative effects of gum Arabic and Boswellia sp. against ARF induced by glycerol or paracetamol as evidenced by restoring the kidney function tests such as urea, creatinine, blood electrolytes and other parameters like serum glucose, proteins and hematological indices to their normal values during the experiment period. The therapeutic effects of both plants against ARF may be due to their antioxidant and/or anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

A new series of 6-(4-fluorophenyl)-2-(methylthio) pyrimidine-5-carbonitrile derivatives were designed and synthesized as EGFR/PI3K dual inhibitors, and potential antiproliferative agents. The new 22 compounds were screened by DTP-NCI against all NCI60 cell lines. Almost all compounds showed cytotoxic activity. Compound 7c showed a promising antitumour activity on CNS cancer (SNB-75), and ovarian cancer (OVAR-4) with IC 50  < 0.01, and 0.64 µM, respectively. Fortunately, 7c exhibited a better safety profile on normal cells (WI-38) than doxorubicin by 2.2-fold. Compound 7c displayed selective inhibitory activity on EGFR t790m over EGFR WT with IC 50  = 0.08, and 0.13 µM, respectively, wherefore it might overcome EGFR-TKIs resistance. In addition to its remarkable inhibitory activity on all PI3K isoforms, specifically PI3K-δ with IC 50  = 0.64 µM Compared with LY294002 IC 50  = 7.6 µM. Compound 7c arrested the cell cycle of SNB-75 & OVAR-4 at the G0-G1 phase coupled with apoptosis induction. The western blotting analysis approved decreasing the expression level of p-AKT coupled with an increase in Casp3, Casp9, and BAX proteins in the SNB-75 & OVAR-4 after being treated with 7c which may support the suggested mechanism of action of 7c as EGFR/PI3K dual inhibitor. Physicochemical parameters were forecasted using SwissADME online tool. MD showed the interaction of 7c with the crucial amino acids of the active domain of both EGFR/PI3K which may explain its potent inhibitory activities. In vivo study disclosed a significant decrease in tumor weight and the number of nodules in the group of mice treated with 7c compared with the control group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A novel series of pyrimidine-5-carbonitrile derivatives was designed, synthesized, then evaluated for their cytotoxic activity as novel anti-cancer with dual EGFR WT /COX-2 inhibitors. Two compounds 4e and 4f disclosed the highest activity against all NCI60 panel cell lines. They were most potent against Colo 205 (IC 50 = 1.66, and 1.83 μM), Sequentially. The most potent two compounds disturbed cell cycle of Colo-205 cells by blocking the G1 phase, coupled with increased annexin-Vstained cells which indicated the increasing in percentage of apoptosis. In addition, 4e and 4f increase the concentration of caspase-3 by 10, and 8-fold compared to control, respectively. Moreover, the two candidate compounds were screened for cytotoxicity on normal epithelial colon cells; fortunately, they were found to be safe. Molecular docking study displayed that these compounds bound to the active site as EGFR WT /COX-2 inhibitors. Furthermore, 3D pharmacophore mapping disclosed many shared features between the most potent candidates 4e and 4f and the standard EGFR WT /COX-2 inhibitors; erlotinib, and celecoxib, respectively. Finally, the physicochemical parameter was calculated for the most potent novel anticancer candidates and the SwissAdme parameter showed that the newly synthesized compounds have good drug-likeness properties., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Objective: To investigate the prevalence of depression, anxiety, and stress symptoms in Jordanian midwives and identify associated factors., Design: Setting and participants: This descriptive, cross-sectional study was conducted with a sample of 321 registered midwives from 18 public hospitals in Jordan that provide antepartum, intrapartum, postpartum care, and family planning services. The survey included the Depression, Anxiety, and Stress Scale (DASS-21) and demographic and professional data forms., Findings: High rates of depression (76.2%); anxiety (85.3%) and stress (66.8%) symptoms were reported among midwives in Jordan. Midwives aged between 22 - 30 years reported more depression, anxiety, and stress symptoms than midwives in the other age groups. Married midwives had higher depression symptoms than single midwives. Midwives with < 10 years in practice had higher depression, anxiety, and stress symptoms compared to midwives with ≥ 10 years in practice. Midwives providing care for > 10 women per shift had higher anxiety and stress symptoms than midwives caring for five or less women per shift. Midwives who rotated between shifts had higher depression and stress symptoms than midwives who did not rotate., Conclusions: Rates of depression, anxiety, and stress symptoms reported by Jordanian midwives were higher than rates reported by midwives in other countries. The high rates of distress highlight the urgent need for national strategies to support the emotional wellbeing and retention of midwives within Jordanian settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Treatment of breast cancer by paclitaxel (PAX) often encounters therapeutic failure most likely caused by innate/acquired resistance. Cancer stem cells (CSCs) and multidrug resistance complex (MDR-1 or P-glycoprotein) overexpression are main mechanisms implicated in chemoresistance. Increased aldehyde dehrogenase-1 (ALDH-1) was previously correlated with the stemness features of CSCs and hence is used as a marker for identification and CSCs targeting. The present study, therefore, aimed at investigating the effect of both curcumin (CUR) and vitamin D3 (D3) on MDR-1 and ALDH-1 expression and consequently the resistance to PAX both in vitro and in vivo. CUR was isolated from Turmeric rhizomes and identified using UPLC-ESI-MS/MS. For in vitro studies, the antiproliferative effect of PAX, CUR, 1,25(OH)2D3 (the active form of D3, also known as calcitriol) was determined, each alone and combined (PAX+CUR, PAX+1,25(OH)2D3, and PAX+CUR+1,25(OH)2D3) on MCF-7 breast cancer cells. Ehrlich ascites carcinoma solid tumor animal model was also used for in vivo studies. Combining CUR and/or 1,25(OH)2D3 to PAX showed synergistic cytotoxic interaction on MCF-7 cells. The apoptotic potential was also enhanced, as evidenced by a significant increase in caspase-7 and -9 as well as the pro-apoptotic Bax whereas a decrease in Bcl-2 levels was reported. Combining CUR and 1,25(OH)2D3 to PAX caused a downregulation in both MDR-1 and ALDH-1 gene expression in MCF-7 besides a decrease in their protein levels. In vivo, the triple therapy group (PAX+CUR+D3) showed the least tumor size. It also showed the lowest levels of MDR-1 and ALDH-1. PAX alone, however, showed increased levels of MDR-1 and ALDH-1 compared to control. Overall, the present study showed that PAX, as a monotherapy, demonstrated acquired resistance possibly by increasing MDR-1 expression and enriching CSCs population, as evidenced by increased ALDH-1. However, using CUR and D3 enhanced tumor response to PAX., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pulmonary cryptococcal infection is commonly seen in HIV patients and in patients who have compromised cell mediated immunity. Its occurrence in immunocompetent individuals is uncommon. Here we present a young adult who presented with cough and hemoptysis and is negative for HIV testing and has no clinical and laboratory evidences of conditions compromising his cell mediated immunity. Radiologically manifested as a solitary huge parenchymal mass lesion mimicking lung malignancy. He was finally diagnosed as having pulmonary cryptococcoma after open biopsy. This is an uncommon manifestation of cryptococcoma in immunologically competent patient.

1. In order to demonstrate that triiodothyronine affects mitochondrial RNA synthesis by acting on the enzyme component of the DNA. RNA polymerase complex, mitochondrial RNA polymerase from thyroidectomized and hormone-treated rats was purified up to a stage in which activity was dependent on the addition of exogenous template. In these conditions and using different DNAs as templates, the enzyme from hormone-treated animals displayed an activity about double that of the activity of thyroidectomized animals. 2. Measurements of stability of mitochondrial RNA synthesized in vitro suggest, however, that the hormone can act also at the template level in mitochondrial transcription: the RNA population synthesized in vitro from hormone-treated rats is indeed much more enriched in unstable, probably messenger, RNA species. 3. The turnover of mitochondrial messenger RNA is higher after hormone treatment. 4. Adenosine cyclic 3':5'-monophosphate (cAMP) and its dibutyryl derivative added in vitro to mitochondria from thyroidectomized animals do not affect the incorporation of labeled precursor into mitochondrial RNA, suggesting that the level of the cyclic nucleotide in mitochondria is probably not involved in the hormone action. 5. It is concluded from these and previous studies that the thyroid hormone affects more than one parameter in the mitochondrial transcription process. The interrelationship between these events at molecular level remains, however, to be clarified.

Liver plays a central role in drug metabolism, particularly in uptake, biotransformation and excretion of metabolites. Among these metabolic steps biotransformation represents the most critical factor in drug-induced liver damage, especially when hepatic protective mechanisms, such as the tripeptide glutathione (GSH), are decreased thereby predisposing to lipid peroxidation of biological membranes. The authors focus on the prevalence of hepatic damage in a population of patients chronically treated with psychotropic drugs and divided according to the therapeutic schedule and the type of drug. It is shown that the liver damage induced by psychopharmacologic treatment correlates in a group of 15 patients with a significant decrease of hepatic glutathione.