Punicalagin prevents cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammatory response, and apoptosis in rats.

Nephrotoxicity is a major complication that limits the therapeutic application of cisplatin (CIS). Oxidative stress and inflammation are implicated in CIS-induced acute kidney injury (AKI) and apoptotic cell death. Punicalagin (PUN), a polyphenol in pomegranate, possesses promising anti-inflammatory and antioxidant activities, and its beneficial effect against CIS-induced AKI has not been fully elucidated. This investigation evaluated the protective effect of PUN against CIS-induced renal oxidative stress, inflammation and cell death. Rats received PUN (25 and 50 mg/kg) for 10 days and a single injection of CIS at day 7. The results showed increased serum urea and creatinine and several histopathological alterations in the kidney of CIS-intoxicated rats. Renal malondialdehyde (MDA) and nitric oxide (NO) were increased, and reduced glutathione, superoxide dismutase and catalase were declined in rats treated with CIS. PUN effectively ameliorated kidney function and attenuated tissue injury induced by CIS, decreased MDA and NO, and enhanced antioxidant defenses. Additionally, PUN downregulated NF-κB p65, iNOS, TNF-α, IL-6 and IL-1ß in the kidney of rats that received CIS. Bax and caspase-3 were increased, and Bcl-2 was decreased in the kidney of CIS-intoxicated rats, an effect that was reversed by PUN. PUN upregulated Nrf2 expression in the kidney of CIS-intoxicated rats. In conclusion, PUN prevents CIS-induced AKI in rats by attenuating oxidative stress, inflammatory response and apoptosis, and upregulating Nrf2 and antioxidants.

Visnagin prevents isoproterenol-induced myocardial injury by attenuating oxidative stress and inflammation and upregulating Nrf2 signaling in rats.

Oxidative tissue injury and inflammatory responses play major roles in cardiovascular diseases and heart failure. Visnagin (VIS) is a natural bioactive component of Ammi visnaga, with promising radical scavenging and anti-inflammatory activities. This study explored the protective effect of VIS against isoproterenol (ISO)-induced acute myocardial injury and oxidative stress in rats. VIS was supplemented for 14 days, and the rats received ISO (100 mg/kg) twice at an interval of 24 h. ISO-induced myocardial injury was characterized by elevated serum CK-MB, LDH, and troponin-I associated with increased heart weight and several histopathological changes. ISO increased reactive oxygen species (ROS), malondialdehyde (MDA), NF-κB p65, TNF-α, IL-6, and decreased glutathione and antioxidant enzymes in rats' hearts. VIS prevented myocardial injury and ameliorated the cardiac function markers, ROS, MDA, NF-κB p65, and pro-inflammatory cytokines in ISO-intoxicated rats. In addition, VIS decreased Bax mRNA and caspases, and upregulated Nrf2, HO-1, Bcl-2, and PPARγ. Molecular docking simulations revealed the binding method of VIS to NF-κB, Keap1, and PPARγ. In conclusion, VIS protects against ISO-induced acute myocardial injury by attenuating oxidative tissue injury and reducing key inflammatory and apoptosis markers. In vivo and in silico results showed that activation of Nrf2/HO-1 signaling and PPARγ mediates the cardioprotective effect of VIS.

Galangin attenuates diabetic cardiomyopathy through modulating oxidative stress, inflammation and apoptosis in rats.

Cardiovascular complications are the leading cause of morbidity in diabetes. Oxidative stress and inflammation are implicated in the development and progression of diabetic cardiomyopathy (DCM). This study explored the cardioprotective effect of galangin (Gal), a natural flavonoid with radical-scavenging and anti-inflammatory activities, in diabetic rats. An experimental diabetic rat model was achieved by a single injection of 50 mg/kg streptozotocin. Gal (15 mg/kg) was administered daily for six weeks and the samples were then collected. Diabetic rats exhibited hyperglycemia, increased glycosylated hemoglobin, triglycerides and cholesterol levels and reduced serum insulin. Serum troponin I, CK-MB and LDH were increased in diabetic rats. Furthermore, hearts of diabetic rats were characterized by elevated malondialdehyde, protein carbonyl, NF-κB p65, TNF-α, IL-1ß, iNOS, IL-6, Bax, caspase-3 and 8-Oxo-dG, and decreased superoxide dismutase, catalase, reduced GSH, and Bcl-2. Gal ameliorated hyperglycemia, dyslipidemia, and heart function markers, and prevented histopathological alterations in diabetic rats. In addition, Gal attenuated cardiac oxidative injury, inflammation and apoptosis, and boosted antioxidant defenses. In conclusion, Gal has a protective effect on cardiomyopathy by attenuating hyperglycemia, dyslipidemia, oxidative stress and inflammation in diabetic rats.

In silico anti-fungal efficacy and the mechanism of binding of some Syzygium aromaticum ingredient compounds to aspartate semialdehyde dehydrogenase, 6C8W and 6C85, enzymes from Blastomyces dermatitidis.

This in silico work was carried out to reveal the proposed anti-fungal efficacy of some clove ingredient compounds against aspartate semialdehyde dehydrogenase, 6C8W and 6C85, enzymes from Blastomyces dermatitidis. The molecular docking simulation was implemented utilizing the Auto Dock 4.2. software. A set of 17 compounds were selected for this study, which is known to be active ingredients of Syzygium aromaticum crude and oil. The best docking scores associated with the Blastomyces dermatitidis enzymes 6C85 and 6C8W were for Maslinic acid and Oleanolic acid, followed by Stigmasterol and Campesterol. It was found that these compounds possess inhibitory potential against 6C85 and 6C8W and hence have anti-fungal efficacy. Maslinic acid and Oleanolic acid produced the strongest binding to 6C85 and 6C8W over the remaining bioactive compounds by forming H-bonds with some amino acids in these enzymes.

Vitamin D is a potential inhibitor of COVID-19: In silico molecular docking to the binding site of SARS-CoV-2 endoribonuclease Nsp15.

Novel coronavirus disease (COVID-19) has become a pandemic threat to public health. Vaccines and targeted therapeutics to prevent infections and stop virus proliferation are currently lacking. Endoribonuclease Nsp15 plays a vital role in the life cycle, including replication and transcription as well as virulence of the virus. Here, we investigated Vitamin D for its in silico potential inhibition of the binding sites of SARS-CoV-2 endoribonuclease Nsp15. In this study, we selected Remdesivir, Chloroquine, Hydroxychloroquine and Vitamin D to study the potential binding affinity with the putative binding sites of endoribonuclease Nsp15 of COVID-19. The docking study was applied to rationalize the possible interactions of the target compounds with the active site of endoribonuclease Nsp 15. Among the results, Vitamin D was found to have the highest potency with strongest interaction in terms of LBE, lowest RMSD, and lowest inhibition intensity Ki than the other standard compounds. The investigation results of endoribonuclease Nsp15 on the PrankWeb server showed that there are three prospective binding sites with the ligands. The singularity of Vitamin D interaction with the three pockets, particularly in the second pocket, may write down Vitamin D as a potential inhibitor of COVID-19 Nsp15 endoribonuclease binding sites and favour addition of Vitamin D in the treatment plan for COVID-19 alone or in combination with the other used drugs in this purpose, which deserves exploration in further in vitro and in vivo studies.

Students' perspective of bedside teaching: A qualitative study.

OBJECTIVES: To determine students' perception of bedside teaching, to find out barriers in its effective implementation and to suggest strategies to make it an effective learning tool. METHODS: This study was conducted in Faculty of Medicine, Northern Border University Arar, Kingdom of Saudi Arabia between November 2013 and January 2014. The study design was qualitative inductive thematic analysis using transcripts from audio-recorded focus group discussions. Four focused group discussions with medical students of 4(th) and 5(th) year MBBS were conducted. Each 40 to 50 minutes discussion session was audio taped and transcribed verbatim. Thematic analysis extracted key themes pertaining to objectives of the study. RESULTS: A total 75 students of 4(th) and 5(th) year MBBS took part in the study, 48 were female and 27 of them were male. Students believed that bedside teaching is valuable for learning essential clinical skills. They described many barriers in its effective implementation: uncooperative and less number of patients and faculty attitude. Our students suggested various strategies to address these barriers: promotion of awareness among general public about students' learning and its benefits, free medical treatment for expatriates and building of university hospital. CONCLUSION: Bedside teaching is an important learning tool. Its utility can be enhanced by orienting local patients' attitude towards importance of students' learning, by providing free medical treatment to expatriates and by including bedside teaching in faculty development programs.

Frequency of obesity and comorbidities in medical students.

OBJECTIVES: To determine the frequency of obesity disorders and their co-morbidities in medical students. METHODS: This cross-sectional study was conducted in Faculty of Medicine, Northern Border University, Ar'ar, Saudi Arabia. All medical students who consented to participate were included in the study. Their relevant information was recorded on a structured proforma. Weight and height of the participants were measured using calibrated manual weighing scale and Body mass index (BMI) was calculated. The obtained results were interpreted according to classification of body weight disorders. The participants who turned out to be over-weight and obese were further assessed for hypertension, diabetes mellitus and gallstones. The collected data was analyzed using the Statistical Package for Social Science (SPSS) version 20. RESULTS: A total of 405 students participated in study, age range was 19-25 years. Male were 169 (41.7%) and female students were 236(58.3%). Family history of obesity was present in 34.3%. Out of 405 students, 126 were having BMI between 25 and 45.6, among them 34(8.4%) students were obese and 88 (21.7%) were overweight. Sixty two (15.3%) among them were male and 64 (15.8%) female. Fourteen (11.1%) were hypertensive and 9(7.1%) were having gall stones. CONCLUSION: The frequency of obesity among medical students was 8.4%. Increasing frequency of obesity associated with unhealthy life style needs to be controlled at national level to raise a healthy generation and to reduce burden on health economy.

Perceptions of faculty and students regarding Problem Based Learning: A mixed methods study.

OBJECTIVE: To determine perception of faculty and students regarding problem-based learning. METHODS: The study was conducted at Northern Border University, Arar, Kingdom of Saudi Arabia, from May 21to November 21, 2014. Data was collected on a structured close-ended questionnaire from faculty members. Application of problem-based learning by the faculty was assessed through observations of first such session of medical students. Observations were recorded on a structured checklist. Perceptions of students about learning methodology were determined through focused group discussion which was audio-taped and transcribed. Qualitative data was analysed through content analysis and quantitative data through SPSS 16. RESULTS: Of the 60 faculty members, 44(73%) took part in the study. Of them, 35(79.5%) were males and 9(20.5) were females. There were 23(52%) assistant professors and 31(70.45%) were trained in problem-based learning. Overall, 22(50%) faculty members thought that it was better than lecture-based learning; and 32(72.7%) stated that they conducted problem-based learning in classic seven jumps. In focus group discussions, students appreciated learning subject content but could not identify other benefits of problem-based learning. CONCLUSIONS: Faculty still had to come to terms with application of problem-based learning methodology.

Histopathological examination of appendicectomy specimens at a district hospital of Saudi Arabia.

BACKGROUND AND OBJECTIVE: Appendicectomy for acute appendicitis is one of the most commonly performed surgical procedures. Acute appendicitis has remained a clinical entity and an ongoing diagnostic challenge. A retrospective study was performed to determine histological diagnosis, demographic data, the rate of perforated appendicitis and negative appendicectomies. METHODS: Histopathological records of 480 resected appendices submitted to histopathology department at Arar Central Hospital in the Northern Border Province of Saudi Arabia over the period of 3 years from July 2011 to June 2014 were reviewed retrospectively, to determine acute appendicitis, complication (gangrene, perforation) rate, negative appendicectomy rate, histopathological diagnosis and unusual finding on histology. RESULTS: Out of 480 specimens of appendix, appendicitis accounted for 466 (97.0%) with peak occurrence in the age group of 11 to 50 years in male and 11 to 40 years in female. Histopathological diagnosis include acute appendicitis 250 (52.0%), suppurative appendicitis 135 (28.0%) acute gangrenous appendicitis 60 (12.5%), perforated appendicitis 9 (2.0%), chronic appendicitis 12 (2.5%). Negative appendicectomy rate was 14 (3%) and two time more common in female with peak occurrence in the age group of 20-30 yrs. There was no unusual histological finding like carcinoid tumour of appendix. CONCLUSION: The present study showed a high number of appendicitis in adolescents and young adults. Negative appendectomy was more common in females. The study support routine histological examination of all the appendicectomy specimens to avoid missing of any clinically important and treatable condition.

Risk factors for diabetic foot ulcer.

BACKGROUND: Diabetic foot is one of the common complications of diabetes mellitus. Many risk factors are involved in its causation. This study was conducted to determine risk factors responsible for foot ulcer in diabetic patients. METHODS: A total of 196 consecutive patients with diabetic foot were included in the study. Detailed history, clinical findings and investigations were recorded. Lesions were graded according to Wagner's classification, and appropriate medical and/or surgical treatment was carried out. Patients who did not consent to participate in the study had established gangrene of the foot, or had any medical co-morbidity especially chronic heart failure and chronic renal failure which could influence these risk factors were excluded from the study. Data were collected on a special proforma for analysis. RESULTS: Out of 196 patients 80.1% were male. One hundred and forty-six (74.48%) patients were in the range of 40-70) years. Right foot was more commonly involved (65.3%). 91.3% patients had diabetes of more than 5 years duration. No treatment had been received by 47.4% patients while 41.3% were on oral anti-diabetics; 11.2% patients were on insulin. All patients had type 2 diabetes mellitus. Neuropathy was present in 51% patients, 62.8% had absent or diminished peripheral pulses, 43.4% had poorly controlled diabetes. According to the Wagner classification 30.6% patients had grade 1, 26.5% had grade 2, and 42.9% had grade 3 diabetic foot. Evidence of infection was seen in 85.7% patients: staphylococcus aureus was isolated in 43.4% patients. Osteomyelitis was present in 42.9% patients. Surgical intervention was performed in 85.7% patients. Direct relation was found between the duration of diabetes, sugar control, peripheral neuropathy, peripheral arterial disease. grade of diabetic foot, evidence of osteomyelitis, intervention and the outcome of the disease. CONCLUSION: Neuropathy, peripheral arterial disease, duration of diseases and undlerlying osteomylitis are the major risk factors and need to addressed while educating patients.

Cellular and molecular responses of Saudi chronic myeloid leukaemia patients to imatinib (STI-571): ten year experience.

BACKGROUND: The cyto-genetic hallmark of chronic myeloid leukaemia (CML), the Philadelphia chromosome (Ph), is the first consistent chromosomal abnormality that has been associated to a certain cancer type. In CML, Philadelphia chromosome is present leading to resistance to cell death and rapid proliferation. The aim of this study is to evaluate the different responses, toxicity and survival of Saudi CML patients to imatinib mesylate. METHODS: All newly diagnosed CML patients who were treated with imatinib were included in this study. We investigated haematological, and molecular and cytogenetic responses by CBC, FISH and RT-PCR respectively. Cell proliferation and apoptosis were assayed using AUC and TUNEL respectively. RESULTS: Of the 12 cases, 9 (75%) were males and 3 (25%) were female. Four (33%) of the cases were diagnosed incidentally and 8 cases (67%) presented mainly with fatigue (75%), fever (58%), and splenomegaly (83%). Signs of bleeding and rashes were rare at presentation. The majority of patients had low risk (8, 67%), and 33% had intermediate risk; but none of them had high risk CML. At the last follow up, 11 (92%) were in remissions. One patient (8%) was in remission after 3 years, 4 (33%) were in remission after 6 years, one was in remission after 7 years and 5 (42%) were in remission after 10 years. Only one patient had incomplete major molecular response (MMR) to imatinib after 12 years. The majority of the patients (10, 83%) were in MMR after 6 years and 42% of them were in MMR after 10 years of therapy. Adverse effects of imatinib were not reported by the patients. Imatinib treatment resulted in the reduction of proliferation and induction of apoptosis of CML CFU-GM cells. CONCLUSION: Imatinib mesylate is capable of treating Philadelphia chromosome-positive CP-CML without any adverse effects.