α-Bisabolol: A Dietary Sesquiterpene that Attenuates Apoptotic and Nonapoptotic Cell Death Pathways by Regulating the Mitochondrial Biogenesis and Endoplasmic Reticulum Stress-Hippo Signaling Axis in Doxorubicin-Induced Acute Cardiotoxicity in Rats.

The potential for multiorgan toxicities is a significant barrier to the therapeutic use of doxorubicin (DOX) in cancer treatment. With regard to DOX-induced acute cardiotoxicity in rats, the current investigation sought to assess the cardioprotective function of α-bisabolol (BSB) as well as the underlying pharmacological and molecular processes. Acute cardiotoxicity was induced in the rats by the intraperitoneal injection of DOX (12.

Cannabinoid 2 Receptor Activation Protects against Diabetic Cardiomyopathy through Inhibition of AGE/RAGE-Induced Oxidative Stress, Fibrosis, and Inflammasome Activation.

Oxidative stress, fibrosis, and inflammasome activation from advanced glycation end product (AGE)-receptor of advanced glycation end product (RAGE) interaction contribute to diabetic cardiomyopathy (DCM) formation and progression. Our study revealed the impact of -caryophyllene (BCP) on activating cannabinoid type 2 receptors (CB2Rs) against diabetic complication, mainly cardiomyopathy and investigated the underlying cell signaling pathways in mice. The murine model of DCM was developed by feeding a high-fat diet with streptozotocin injections.

Students' perspectives on their early dropout of medical school.

Background: Enrolling in medical school launches a more demanding and stressful way of life for newly admitted students. Some students will struggle academically and will ultimately drop out from medical school. The study aims to understand the perspectives that dropped-out students have and their opinion regarding possible preventative solutions.

Relationship between admission selection tools and student attrition in the early years of medical school.

Objectives: Placement in medical schools is highly sought after worldwide with fierce competition among applicants. However, some of the best students withdraw after being accepted to medical school. The aim of this study was to investigate early student attrition within the first 2 years of medical school and determine its relationship to admission selection tools.

Long-Lasting Complete Remission in a Patient With Metastatic Metaplastic Breast Cancer Treated With Immune Checkpoint Inhibitor and Chemotherapy: A Case Report and a Review of the Literature.

Metaplastic breast cancer (MpBC) is a rare form of breast cancer known for suboptimal response to chemotherapy, high recurrence rate, poor prognosis, and limited treatment options. Recent studies have reported that MpBC has high expression of programmed death ligand 1 and tumor-infiltrating lymphocytes, indicating the potential effectiveness of immunotherapy (IO) in MpBC. In addition, several reports have demonstrated the activity of IO in MpBC.

α-Bisabolol, a Dietary Sesquiterpene, Attenuates Doxorubicin-Induced Acute Cardiotoxicity in Rats by Inhibiting Cellular Signaling Pathways, Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 Inflammasomes Regulating Oxidative Stress and Inflammatory Cascades.

Cancer chemotherapy with doxorubicin (DOX) may have multiorgan toxicities including cardiotoxicity, and this is one of the major limitations of its clinical use. The present study aimed to evaluate the cardioprotective role of α-Bisabolol (BSB) in DOX-induced acute cardiotoxicity in rats and the underlying pharmacological and molecular mechanisms. DOX (12.

Metformin Suppresses Thioacetamide-Induced Chronic Kidney Disease in Association with the Upregulation of AMPK and Downregulation of Oxidative Stress and Inflammation as Well as Dyslipidemia and Hypertension.

Toxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are reported to induce hepato-nephrotoxicity. The potential protective outcome of the antidiabetic and pleiotropic drug metformin against TAA-induced chronic kidney disease in association with the modulation of AMP-activated protein kinase (AMPK), oxidative stress, inflammation, dyslipidemia, and systemic hypertension has not been investigated before. Therefore, 200 mg/kg TAA was injected (via the intraperitoneal route) in a model group of rats twice a week starting at week 3 for 8 weeks.

Lower Prevalence of Human Papillomavirus in Head and Neck Squamous Cell Carcinoma in Middle Eastern Population: Clinical Implications for Diagnosis and Prevention.

Introduction Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The prevalence of human papillomavirus (HPV) in HNSCC varies across regions. Objective This study aimed to determine the prevalence of high-risk HPV (hrHPV) among patients with HNSCC in the Middle East region.

Lower Extremity Arterial Disease in Type 2 Diabetes Mellitus: Metformin Inhibits Femoral Artery Ultrastructural Alterations as well as Vascular Tissue Levels of AGEs/ET-1 Axis-Mediated Inflammation and Modulation of Vascular iNOS and eNOS Expression.

Lower extremity arterial disease (LEAD) is a major risk factor for amputation in diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 (ET-1)/nitric oxide synthase (NOS) axis-mediated femoral artery injury with and without metformin has not been previously investigated. Type 2 diabetes mellitus (T2DM) was established in rats, with another group of rats treated for two weeks with 200 mg/kg metformin, before being induced with T2DM.

Effect of Sirolimus/Metformin Co-Treatment on Hyperglycemia and Cellular Respiration in BALB/c Mice.

Sirolimus (SRL) is widely used as an immunosuppressant to prevent graft rejection, despite the risk of impairing glucose metabolism. Metformin (MET) can reduce the detrimental effects of SRL in many patients, including diabetes and renal transplant recipients. Limited in vivo studies have reported on SRL and MET therapy, particularly in relation to cellular bioenergetics, glucose metabolism, and insulin resistance.

α-Bisabolol Attenuates NF-κB/MAPK Signaling Activation and ER-Stress-Mediated Apoptosis by Invoking Nrf2-Mediated Antioxidant Defense Systems against Doxorubicin-Induced Testicular Toxicity in Rats.

The present study investigated the effects of α-bisabolol on DOX-induced testicular damage in rats. Testicular damage was induced in rats by injecting DOX (12.5 mg/kg, i.

α-Bisabolol Attenuates Doxorubicin Induced Renal Toxicity by Modulating NF-κB/MAPK Signaling and Caspase-Dependent Apoptosis in Rats.

Doxorubicin (DOX) is a well-known and effective antineoplastic agent of the anthracycline family. But, multiple organ toxicities compromise its invaluable therapeutic usage. Among many toxicity types, nephrotoxicity is one of the major concerns.

Sirolimus treatment induces dose-dependent involution of the thymus with elevated cellular respiration in BALB/c mice.

Several and studies have shown that the mammalian target of rapamycin (mTOR) inhibitor sirolimus (rapamycin) suppresses thymus cellular respiration. The objective of this study is to investigate the chronic dose-dependent effects of sirolimus in the thymus. This was monitored using body weight, histomorphology, caspase-3 expression, cytochrome C immunohistochemistry, and cellular bioenergetics as surrogate biomarkers.

Copy Number Profiles of Prostate Cancer in Men of Middle Eastern Ancestry.

Our knowledge of prostate cancer (PCa) genomics mainly reflects European (EUR) and Asian (ASN) populations. Our understanding of the influence of Middle Eastern (ME) and African (AFR) ancestry on the mutational profiles of prostate cancer is limited. To characterize genomic differences between ME, EUR, ASN, and AFR ancestry, fluorescent in situ hybridization (FISH) studies for deletion and MYC amplification were carried out on 42 tumors arising in individuals of ME ancestry.

Effect of angiotensin II on diabetic glomerular hyperpermeability: an in vivo permeability study in rats.

Angiotensin II drives the pathogenesis of diabetic kidney disease, and its systemic administration induces glomerular hyperpermeability in normal rats. However, the response of diabetic glomerular permeability to angiotensin II is largely unknown. In the present study, we investigated the impact of extended systemic administration of angiotensin II on the glomerular permeability of streptozotocin (STZ)-induced late diabetes in rats.

1,2,3-Triazolyl ester of ketorolac (15K), a potent PAK1 blocker, inhibits both growth and metastasis of orthotopic human pancreatic cancer xenografts in mice.

More than 90% of human pancreatic cancers carry the oncogenic mutant of Ki-RAS and their growth depends on its downstream kinase PAK1, mainly because PAK1 blocks the apoptosis of cancer cells selectively. We developed a highly cell-permeable PAK1-blocker called 15K from an old pain-killer (ketorolac), that is shown here to inhibit the growth of three pancreatic cancer cell lines with IC50 values ranging 41-88 nM in vitro. The anti-cancer effect of 15K was further investigated in an orthotopic xenograft model with gemcitabine (GEM)-resistant human pancreatic cancer cell lines (AsPC-1 and BxPC-3) expressing luciferase in athymic mice.

Possible acute rejection associated with the use of the new anti-hepatitis C virus medications.

Hepatitis C virus infection is associated with increased morbidity and mortality. It remains a major challenge for management and treatment, especially in patients with renal transplant. The new direct-acting antiviral agents gave big hopes to both clinicians and patients that they can overcome this challenge without major side effects.

Frequency of rare and multi viral high-risk HPV types infection in cervical high grade squamous intraepithelial lesions in a non-native dominant middle eastern country: a polymerase chain reaction-based pilot study.

Background: The incidence of abnormal cervical smears in the United Arab Emirates (UAE) is 3.6%. Data regarding specific high-risk HPV (hrHPV) genotypes are insufficient.

Gallbladder Polyps in Metachromatic Leukodystrophy.

Background: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease, caused by a deficiency of arylsulfatase A, and leads to demyelination of the nervous system. A putative association between MLD and gallbladder pathology including malignancy is documented in the medical literature.

Case Report: A 10-year-old boy with MLD was found to have a papillary growth within a cystically dilated gallbladder.

Swim exercise training ameliorates hepatocyte ultrastructural alterations in rats fed on a high fat and sugar diet.

Excessive consumption of carbohydrate and fat increases the risk of liver disease. We hypothesized that swim exercise can protect hepatocytes from ultra-structural damage induced by high cholesterol and fructose diets (HCFD). Rats were either fed with HCFD (model group) or a standard laboratory chow (control group) for 15 weeks before being sacrificed.

Deficiency of mitochondrial modulator MCJ promotes chemoresistance in breast cancer.

Despite major advances in early detection and prognosis, chemotherapy resistance is a major hurdle in the battle against breast cancer. Identifying predictive markers and understanding the mechanisms are key steps to overcoming chemoresistance. Methylation-controlled J protein (MCJ, also known as DNAJC15) is a negative regulator of mitochondrial respiration and has been associated with chemotherapeutic drug sensitivity in cancer cell lines.

The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration.

The purpose of this in vitro study was to develop a useful biomarker (e.g., cellular respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors.

The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration.

The purpose of this in vitro study was to develop a useful biomarker (e.g., cellular respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors.

Mammary carcinoma with osteoclast-like giant cells: a case report.

Mammary carcinoma with osteoclast-like giant cells is rare, and comprises less that 2% of breast carcinoma cases. Herein, we present a case of a 45-year-old woman who underwent breast lumpectomy and sentinel lymph node biopsy for a solitary well defined breast tumor. Histological examination revealed an invasive tumor composed of ducts, small nests and cribriform formations intermixed with a prominent osteoclast like giant cell component.

Effects of molecularly targeted therapies on murine thymus: highly selective mTOR inhibitors induce reversible thymic involution.

Background: Blocking mTOR (molecular target of rapamycin) by sirolimus has been shown to suppress cellular respiration. The bearing of this impaired cellular bioenergetics on the mode-of-action of mTOR inhibitors has yet to be illustrated.

Methods: This study investigated in vitro effects of several molecularly-targeted therapies on O2 consumption in thymic fragments from C57BL/6 mice.