Biochemical and histological evidences for the antitumor potential of Teucrium Oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma

Background: Teucrium oliverianum and Rhazya stricta are medicinal plants used in traditional and herbal medicine for the treatment of diabetes, liver diseases and inflammatory conditions. The present study was planned to investigate the antitumor efficacy of Teucrium oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma (HCC) in rats.Materials and Methods: Forty adult male rats weighing 170-200 g were divided into four groups; each group was comprised of ten rats: (1): Normal healthy animals served as negative control group, (2):  Hepatocellular carcinoma (HCC) group in which the rats were orally administered Nnitrosodiethylamine (dissolved in 0.9% normal saline), in a dose of 20 mg/kg b.wt. five times a week for six weeks, (3): HCC group treated with Teucrium oliverianum extract in a dose of 600 mg/kg b.wt for two months and (4): HCC group treated with Rhazya stricta extract in a dose of 750 mg/kg b.wt for two months. Serum alanine  aminotransferase (ALT), asparatate aminotransferase (AST), alkaline phosphatase (ALP) and  gammaglutamyl transferase (γ-GT) activities were estimated. Serum  carcinoembyronic antigen (CEA), alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), glypican-3 (GPC-3), golgi protein 73 (Gp-73) and vascular endothelial growth factor (VEGF) levels were determined. Histopathological examination of liver tissue sections was also carried out.Results: The HCC group showed significant elevation in serum AST, ALT, ALP and γ-GT activities as well  as CEA, AFP, AFU, Gpc-3, Gp 73 and VEGF levels versus the negative control group. Photomicrograph of liver tissue sections of rats in HCC revealed hepatic parenchyma with foci of anaplastic hepatocellular carcinoma as well as other foci of cystic cholangio carcinoma associated with areas of telangictasis with haemorrhage as well as individual hepatocellular necrosis.Conclusion: Treatment of HCC groups with Teucrium oliverianum or Rhazya stricta extract experienced significant improvement in the measured biochemical parameters as well as in the structural  organization of the liver. In conclusion, the current study provided experimental evidences for the antitumor efficacy of Teucrium oliverianum and Rhazya stricta against hepatocellular carcinoma. Such effect could be attributed to hepatoprotective properties, antiproliferative activity and antiangiogenic potential.Keywords: Hepatocellular carcinoma, Teucrium oliverianum, Rhazya stricta, rat

NAD(P)H:quinone oxidoreductase 1 inducer activity of some novel anilinoquinazoline derivatives

The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements pathway enables cells to survive oxidative stress conditions through regulating the expression of cytoprotective enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1). This work presents the design and synthesis of novel anilinoquinazoline derivatives (2–16a) and evaluation of their NQO1 inducer activity in murine cells. Molecular docking of the new compounds was performed to assess their ability to inhibit Keap1–Nrf2 protein–protein interaction through occupying the Keap1–Nrf2-binding domain, which leads to Nrf2 accumulation and enhanced gene expression of NQO1. Docking results showed that all compounds can potentially interact with Keap1; however, 1,5-dimethyl-2-phenyl-4-(2-phenylquinazolin-4-ylamino)-1,2-dihydropyrazol-3-one (9), the most potent inducer, showed the largest number of interactions with key amino acids in the binding pocket (Arg483, Tyr525, and Phe478) compared to the native ligand or any other compound in this series

BIOCHEMICAL AND HISTOLOGICAL EVIDENCES FOR THE ANTITUMOR POTENTIAL OF TEUCRIUM OLIVERIANUM AND RHAZYA STRICTA IN CHEMICALLY-INDUCED HEPATOCELLULAR CARCINOMA

Background: Teucrium oliverianum and Rhazya stricta are medicinal plants used in traditional and herbal medicine for the treatment of diabetes, liver diseases and inflammatory conditions. The present study was planned to investigate the antitumor efficacy of Teucrium oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma (HCC) in rats. Materials and Methods: Forty adult male rats weighing 170-200 g were divided into four groups; each group was comprised of ten rats: (1): Normal healthy animals served as negative control group, (2): Hepatocellular carcinoma (HCC) group in which the rats were orally administered Nnitrosodiethylamine (dissolved in 0.9% normal saline), in a dose of 20 mg/kg b.wt. five times a week for six weeks, (3): HCC group treated with Teucrium oliverianum extract in a dose of 600 mg/kg b.wt for two months and (4): HCC group treated with Rhazya stricta extract in a dose of 750 mg/kg b.wt for two months. Serum alanine aminotransferase (ALT), asparatate aminotransferase (AST), alkaline phosphatase (ALP) and gammaglutamyl transferase (γ-GT) activities were estimated. Serum carcinoembyronic antigen (CEA), alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), glypican-3 (GPC-3), golgi protein 73 (Gp-73) and vascular endothelial growth factor (VEGF) levels were determined. Histopathological examination of liver tissue sections was also carried out. Results: The HCC group showed significant elevation in serum AST, ALT, ALP and γ-GT activities as well as CEA, AFP, AFU, Gpc-3, Gp 73 and VEGF levels versus the negative control group. Photomicrograph of liver tissue sections of rats in HCC revealed hepatic parenchyma with foci of anaplastic hepatocellular carcinoma as well as other foci of cystic cholangio carcinoma associated with areas of telangictasis with haemorrhage as well as individual hepatocellular necrosis. Conclusion: Treatment of HCC groups with Teucrium oliverianum or Rhazya stricta extract experienced significant improvement in the measured biochemical parameters as well as in the structural organization of the liver. In conclusion, the current study provided experimental evidences for the antitumor efficacy of Teucrium oliverianum and Rhazya stricta against hepatocellular carcinoma. Such effect could be attributed to hepatoprotective properties, antiproliferative activity and antiangiogenic potential

Effect of redo varicocelectomy on semen parameters and pregnancy outcome: An original report and meta-analysis

Recurrence following varicocelectomy is an important cause of treatment failure and persistence of subnormal semen parameters. This original study was combined with a systemic review and meta-analysis aiming to evaluate the efficacy of redo varicocelectomy on male fertility potential and pregnancy outcome. The retrospective study included 32 patients who underwent microsurgical subinguinal varicocelectomy for patients with recurrent varicocele. Changes in semen parameters and hormone profiles before and after surgery were compared. The literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and included seven articles in addition to our original report. Results of the original study revealed statistically significant improvements in sperm concentration, progressive motility, total motile sperm count and normal morphology following redo varicocelectomy. The meta-analysis results echoed those reported in our original study and depicted significant improvements in sperm concentration (mean difference [MD] = +20.281 million/ml, p < 0.001), total motility (MD = +9.659%, p = 0.001), total motile sperm count (MD = +23.258 million sperm, p < 0.001) and normal morphology (MD = +4.460%, p < 0.001). Overall pregnancy outcome was reported in seven studies with a rate of 34.6%. No significant changes were noted in any of the collected hormone results both in this original report and in the meta-analysis. In conclusion, redo varicocelectomy has a beneficial role on male fertility potential and can be offered for men with recurrent varicocele as directed by their individual clinical condition

Molecular MRI of Inflammation in Atherosclerosis

Inflammatory activity in atherosclerotic plaque is a risk factor for plaque rupture and atherothrombosis and may direct interventional therapy. Inflammatory activity can be evaluated at the (sub)cellular level using in vivo molecular MRI. This paper reviews recent progress in contrast-enhanced molecular MRI to visualize atherosclerotic plaque inflammation. Various MRI contrast agents, among others ultra-small particles of iron oxide, low-molecular-weight Gd-chelates, micelles, liposomes, and perfluorocarbon emulsions, have been used for in vivo visualization of various inflammation-related targets, such as macrophages, oxidized LDL, endothelial cell expression, plaque neovasculature, MMPs, apoptosis, and activated platelets/thrombus. An enzyme-activatable magnetic resonance contrast agent has been developed to study myeloperoxidase activity in inflamed plaques. Agents creating contrast based on the chemical exchange saturation transfer mechanism were used for thrombus imaging. Transfer of these molecular MRI techniques to the clinic will critically depend on the safety profiles of these newly developed magnetic resonance contrast agents

Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices

Purpose: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. Materials and methods: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. Results: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. Conclusions: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Addressing global disparities in blood pressure control: perspectives of the International Society of Hypertension

Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework