Validation of the Antiproliferative Effects of Organic Extracts from the Green Husk of Juglans regia L. on PC-3 Human Prostate Cancer Cells by Assessment of Apoptosis-Related Genes

With the increased use of plant-based cancer chemotherapy, exploring the antiproliferative effects of phytochemicals for anticancer drug design has gained considerable attention worldwide. This study was undertaken to investigate the effect of walnut green husk extracts on cell proliferation and to determine the possible molecular mechanism of extract-induced cell death by quantifying the expression of Bcl-2, Bax, caspases-3, and Tp53. PC-3 human prostate cancer cells. In this study, we found that green husk extracts suppressed proliferation and induced apoptosis in a dose- and time-dependent manner by modulating expression of apoptosis-related genes. This involved DNA fragmentation (determined by TUNEL assay) and significant changes in levels of mRNA and the expression of corresponding proteins. An increase in expressions of Bax, caspase-3, and tp53 genes and their corresponding proteins was detected using real-time PCR and western blot analysis in PC-3 cells treated with the green husk organic extracts. In contrast, Bcl2 expression was downregulated after exposure to the extracts. Our data suggest the presence of bioactive compound(s) in walnut green husks that are capable of killing prostate carcinoma cells by inducing apoptosis and that the husks are a candidate source of anticancer drugs

Differential Expression Profile and Genetic Variants of MicroRNAs Sequences in Breast Cancer Patients

The technology available for cancer diagnosis and prognosis is not yet satisfactory at the molecular level, and requires further improvements. Micro RNAs (miRNAs) have been recently reported as useful biomarkers in diseases including cancer. We performed a miRNA expression profiling study using peripheral blood from breast cancer patients to detect and identify characteristic patterns. A total of 100 breast cancer patients and 89 healthy patients were recruited for miRNA genotyping and expression profiling. We found that hs-miR-196a2 in premenopausal patients, and hs-miR-499, hs-miR-146a and hs-miR-196a2 in postmenopausal patients, may discriminate breast cancer patients from healthy individuals. In addition, we found a significant association between two microRNA polymorphisms (hs-miR-196a2 and hs-miR-499) and breast cancer risk. However, no significant association between the hs-miR-146a gene and breast cancer risk was found. In summary, the study demonstrates that peripheral blood miRNAs and their expression and genotypic profiles can be developed as biomarkers for early diagnosis and prognosis of breast cancer

Prevalence of different tick species on livestock and associated equines and canine from different agro-ecological zones of Pakistan

Ticks are ectoparasites that act as vectors for transmission of various pathogens to wild and domesticated animals and pose a serious threat to human health. Because of the hot and humid conditions in different agro-ecological zones of Pakistan, ticks are abundant and parasitize a variety of animals. The aim of this study was to identify different tick species and distribution on different hosts especially livestock, such as sheep, goat, cattle, buffalo, and camel, and livestock associated canines and equines, such as horse, donkey, and dog, across different agro-ecological zones of Pakistan. The ticks samples were collected and morphologically identified at genus and species level using morphological keys under stereomicroscope. A total of 2,846 animals were examined for the tick infestation, and 408 animals were tick-infested. Eleven tick species belonging to 4 genera were identified: Hyalomma anatolicum, Hyalomma scupense, Hyalomma dromedarii, Hyalomma isaaci, Rhipicephalus microplus, Rhipicephalus haemaphysaloides, Rhipicephalus turanicus, Haemaphysalis cornupunctata, Haemaphysalis montgomeryi, Haemaphysalis bispinosa, and Ixodes kashmiricus. The overall tick prevalence was 14.3%; host-wise infestation rate was 12.2% in sheep; 12.6%, goat; 11.7%, buffalo; 11.7%, cattle; 19.6%, camel; 27.4%, donkey; 23.5%, horse; and 24.3%, dog. Tick infestation of different animals differed on the basis of the zones. Camels showed the highest tick infestation rate in zones 1 and 2 (21.4 and 26.7%, respectively), whereas donkeys showed the highest infestation rate in zones 3, 4, 6, and 7 (25, 39.3, 3.3, and 21.4%, respectively). The infestation rates of Hyalomma and Rhipicephalus were the highest in zone 2 (71.4 and 52.9%, respectively). The infestation rate of Hyalomma was the highest (47.4%) in sheep; Haemaphysalis (46.9%), goat; Rhipicephalus (69.7%), buffalo; Rhipicephalus (62.3%), cattle; Hyalomma (70%), camel; Ixodes (60.9%), donkey; Ixodes (75%), horse; and Rhipicephalus (61.1%), dog. This study showed the diversity and infestation rate of different ticks with respect to their hosts and agro-ecological zones of Pakistan. High tick burdens and infestation rates are responsible for the spread of different tick-borne infections, resulting in loss of animal productivity and posing a threat to animal and human health. Understanding different tick species and their distribution across different zones will be helpful for developing efficient control strategies against different tick born infections

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A comparative study of the CAPM and extended models in the Indian stock market

To explain the cross section of asset returns, there are numerous asset pricing models being used which require ideal conditions in the markets around the world. An attempt has been made in the present study to estimate and compare the different versions of capital asset princing model (CAPM) using the data of sectoral indices listed in S&P BSE in the Indian stock market. The two widely used approaches i.e. Fama-MacBeth (1973) and Pettengil et al. (1995) for conditional versions have been adopted in the study. The models were compared on the basis of Akaike Information Criterion (AIC) and it was obtained that the AIC value of the Unconditional higher moment CAPM was obtained minimum among other models. Hence it can be said as the better model than other models estimated

Correlation analysis of reactivity in the oxidation of methionine by benzimidazolium fluorochromate in different mole fractions of acetic acid–water mixture

The kinetics of oxidation of methionine (Met) by benzimidazolium fluorochromate (BIFC) has been studied in the presence of chloroacetic acid. The reaction is first order with respect to methionine, BIFC and acid. The reaction rate has been determined at different temperatures and activation parameters calculated. With an increase in the mole fraction of acetic acid in its aqueous mixture, the rate increases. The solvent effect has been analyzed using the Kamlet’s multi parametric equation. A correlation of data with the Kamlet–Taft solvatochromic parameters (α, β, π∗) suggests that the specific solute–solvent interactions play a major role in governing the reactivity. The reaction does not induce polymerization of acrylonitrile. A suitable mechanism has been proposed

Correlation analysis of reactivity in the oxidation of some para- substituted benzhydrols by triethylammonium chlorochromate in non-aqueous media

Triethylammonium chlorochromate (TriEACC) oxidation of some para-substituted benzhydrols (BH) in dimethylsulfoxide (DMSO) leads to the formation of corresponding benzophenones. The reaction was run under pseudo-first-order conditions. The reaction is catalyzed by hydrogen ions. The hydrogen ion dependence has the form: kobs = a + b[H+]. Various thermodynamic parameters for the oxidation have been reported and discussed along with the validity of isokinetic relationship. Oxidation of benzhydrol was studied in 18 different organic solvents. The rate data showing satisfactory correlation with Kamlet–Taft solvatochromic parameters (α, β and π∗) suggests that the specific solute–solvent interactions play a major role in governing the reactivity, and the observed solvent effects have been explained on the basis of solute–solvent complexation. A suitable mechanism of oxidation has been proposed

An efficient one-pot multicomponent synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/thiones/imines via a Lewis base catalyzed Biginelli-type reaction under solvent-free conditions

3,4-Dihydropyrimidin-2(1H)-one, 3,4-dihydropyrimidin-2(1H)-thione, and 3,4-dihydropyrimidin-2(1H)-imine derivatives were synthesized by modified Biginelli cyclocondensation reaction catalyzed by triphenylphosphine as Lewis base. The structures of the synthesized compounds have been elucidated by IR, 1H NMR and elemental analysis