Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis

Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P<0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen

Assessment of the accuracy of multi-parametric MRI with PI-RADS 2.0 scoring system in the discrimination of suspicious prostatic focal lesions

AbstractObjectivesAssessing the value of Mp-MRI with PI-RAD2.0 in distinguishing between malignant and benign prostatic lesions.Patients & methods55 patients with suspicious prostatic lesions underwent PR examination, PSA tests, TRU/S, and Mp-MRI prostate. Mean age was 62years and imaging data were correlated with histopathological data.ResultsHistopathology results revealed 38 malignant lesions and 17 were benign. DWI showed significant restriction with low ADC value, 0.89±0.24μm2/ms in 30 PZ lesions that diagnosed to be likely malignant, (3–5 score) and 7 benign lesions showed no diffusion abnormality with ADC values, 1.34±0.21μm2/ms which were statistically significantly higher than those of malignant lesions (P<0.001). Of the 18 TZ lesions, T2WI diagnosed 7 to be likely malignant (score 3–5) and 11 were benign (1–2 score). DCE-MRI revealed positive results in 28 PZ and 8 TZ lesions. Adding DCE-MRI to DWI and T2WI score in equivocal lesions raises its score from 3 to 4 in 6/9 lesions that aid in malignant lesions diagnosis. Negative enhancement was noted in 9 PZ and 10 TZ benign lesions (−ve).ConclusionMulti-parametric MRI with PI-RAD V2 scoring system was proved to be non invasive and accurate tool for distinguishing between malignant and benign prostatic lesions

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Selective versus non Selective Cyclooxygenase Inhibitors in High Fructose-Induced Metabolic Syndrome

Metabolic syndrome (MS) is a cluster of interrelated abnormalities namely obesity, dyslipidemia, hypertension, and insulin resistance. Chronic inflammation with release of inflammatory mediators including cyclooxygenase (COX) enzymes represents an important pathogenic factor in the development of MS. The present study investigated the effect of selective COX-2 inhibitor, celecoxib, versus non selective, diclofenac, in prevention of high fructose-induced MS in rats. Rats were divided into 6 groups: normal control (received normal diet); high fructose fed (HF) (received 20% fructose plus saline to serve as control MS group; celecoxib-treated ( received HF plus either celecoxib 10 or 50 mg/kg/day); diclofenac-treated (received HF plus either diclofenac 6 or 30 mg/kg/day). visceral fat index (visceral fat weight /body weight ratio), insulin resistance , serum levels of triglyceride (TG), high density lipoprotein (HDL), malondialdehyde (MDA), reduced glutathione (GSH), catalase, uric acid, C-reactive protein (CRP), and tumor necrosis factor- α (TNF-α) were measured. The results showed that celecoxib, but not diclofenac, prevented the development of high fructose-induced MS as indicated by significant attenuation in visceral fat index, insulin resistance, and lipid profile. The protective effect of celecoxib was associated with significant improvement in serum levels of oxidative stress markers (MDA, GSH, and catalase), and inflammatory markers (uric acid, CRP, and TNF-α). These results indicate that selective COX-2 inhibitors protect against high fructose-induced MS possibly via antioxidant and anti-inflammatory effects