Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects

Cancer remains the topmost disorder of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.     

Regionally selective atrophy of subcortical structures in prodromal HD as revealed by statistical shape analysis

Huntington disease (HD) is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this article, which is based on a dataset extracted from the PREDICT‐HD study, we use statistical shape analysis with deformation markers obtained through “Large Deformation Diffeomorphic Metric Mapping” of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. On the basis of the relation to cortico‐basal ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention. Hum Brain Mapp 35:792–809, 2014. © 2012 Wiley Periodicals, Inc.     

Metastatic Osteosarcoma to the Interventricular Septum: An Unusual Presentation in a Child

Whereas primary cardiac tumors are reported in only 0.17 % of pediatric patients, malignant cardiac tumors are even less common in children. This report presents a 10-year-old child with relapsed osteosarcoma manifesting as metastatic lesions to the interventricular septum.     

Bedside score predicting retained common bile duct stone in acute biliary pancreatitis

BACKGROUND Retained common bile duct(CBD) stone after an acute episode of biliary pancreatitis is of paramount importance since stone extraction is mandatory.AIM To generate a simple non-invasive score to predict the presence of CBD stone in patients with biliary pancreatitis.METHODS We performed a retrospective study including patients with a diagnosis of biliary pancreatitis. One hundred and fifty-four patients were included. Thirty-three patients(21.5%) were diagnosed with CBD stone by endoscopic ultrasound(US).RESULTS In univariate analysis, age(OR: 1.048, P = 0.0004), aspartate transaminase(OR:1.002, P = 0.0015), alkaline phosphatase(OR: 1.005, P = 0.0005), gamma-glutamyl transferase(OR: 1.003, P = 0.0002) and CBD width by US(OR: 1.187, P = 0.0445)were associated with CBD stone. In multivariate analysis, three parameters were identified to predict CBD stone;age(OR: 1.062, P = 0.0005), gamma-glutamyl transferase level(OR: 1.003, P = 0.0003) and dilated CBD(OR: 3.685, P = 0.027),with area under the curve of 0.8433. We developed a diagnostic score that included the three significant parameters on multivariate analysis, with assignment of weights for each variable according to the co-efficient estimate. A score that ranges from 51.28 to 73.7 has a very high specificity(90%-100%) for CBD stones, while a low score that ranges from 9.16 to 41.04 has a high sensitivity(82%-100%). By performing internal validation, the negative predictive value of the low score group was 93%.CONCLUSION We recommend incorporating this score as an aid for stratifying patients with acute biliary pancreatitis into low or high probability for the presence of CBD stone.     

Predictors of thirty-day readmission in nonagenarians presenting with acute heart failure with preserved ejection fraction: a nationwide analysis

BACKGROUDAcute heart failure with preserved ejection fraction (HFpEF) is a common but poorly studied cause of hospital admissions among nonagenarians. This study aimed to evaluate predictors of thirty-day readmission, in-hospital mortality, length of stay, and hospital charges in nonagenarians hospitalized with acute HFpEF.METHODSPatients hospitalized between January 2016 and December 2018 with a primary diagnosis of diastolic heart failure were identified using ICD-10 within the Nationwide Readmission Database. We excluded patients who died in index admission, and discharged in December each year to allow thirty-day follow-up. Univariate regression was performed on each variable. Variables with P-value < 0.2 were included in the multivariate regression model. RESULTSFrom a total of 45,393 index admissions, 43,646 patients (96.2%) survived to discharge. A total of 7,437 patients (15.6%) had a thirty-day readmission. Mean cost of readmission was 43,265 United States dollars (USD) per patient. Significant predictors of thirty-day readmission were chronic kidney disease stage III or higher [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.07−1.34,P = 0.002] and diabetes mellitus (aOR = 1.18, 95% CI: 1.07−1.29,P = 0.001). Meanwhile, female (aOR = 0.90, 95% CI: 0.82−0.99,P = 0.028) and palliative care encounter (aOR = 0.27, 95% CI: 0.21−0.34,P < 0.001) were associated with lower odds of readmission. Cardiac arrhythmia (aOR = 1.46, 95% CI: 1.11−1.93, P = 0.007) and aortic stenosis (aOR = 1.36, 95% CI: 1.05−1.76,P = 0.020) were amongst predictors of in-hospital mortality. CONCLUSIONSIn nonagenarians hospitalized with acute HFpEF, thirty-day readmission is common and costly. Chronic comorbidities predict poor outcomes. Further strategies need to be developed to improve the quality of care and prevent the poor outcome in nonagenarians.

By 2030, it is estimated that one every thirty-three patients will have the diagnosis of heart failure (HF). The projected cost estimates of treating HF are 160 billion United States dollars (USD) in direct costs. Because of the aging of the population, greater increase in HF prevalence will be seen in older adults. It is projected that the number of patients > 80 years with HF will grow by 66% by 2030. ^[1]HF incidence and prevalence rise dramatically with age due to structural and functional alterations in the cardiovascular system, making HF the most prevalent cardiovascular disease among elderly. HF was reported to be the second leading cause of hospitalization for patients aged 75 years and above from 2013 to 2018.^[2]Most elderly patients with HF have impaired left ventricular diastolic function without significant impairment in left ventricular systolic function, which is called heart failure with preserved ejection fraction (HFpEF).^[3–6] Increased levels of brain natriuretic peptide, older age, myocardial infarction history, and reduced diastolic function make the prognosis of HFpEF worse.^[7–9]Over the years, there have been advances in the treatment of HF, however, the mortality, hospitalization, and readmission rates are still high.In this study, we aimed to assess the predictors and causes of readmissions with acute HFpEF among nonagenarians in the United States, by using the National Readmission Database (NRD).     

Mitomycin C application after photorefractive keratectomy in high,moderate, or low myopia: Systematic review and meta-analysis

Photorefractive keratectomy (PRK) is considered a safe approach laser procedure with a clinical significance in correcting myopia results. PRK requires removing the whole superficial epithelium. The integrity of the epithelial basement membrane and the deposition of abnormal extracellular matrix can put the cornea in a probable situation for corneal haze formation. Mitomycin C (MMC) is applied after excimer laser ablation as a primary modulator for wound healing, limiting corneal haze formation. We aim to summarize the outcomes of MMC application after laser ablation. We searched Scopus, PubMed, Cochrane CENTRAL, and Web of Science till December 2020 using relevant keywords. The data were extracted and pooled as mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI), using Review Manager software (version 5.4). Our analysis demonstrated a statistically significant result for MMC application over the control group in terms of corneal haze formation postoperatively (RR = 0.29, 95% CI: [0.19, 0.45], P < 0.00001). Regarding corrected distance visual acuity (CDVA), no significant difference was observed between the MMC group and the control group (MD = 0.02; 95% CI: [-0.04, 0.07]; P = 0.56). Regarding the uncorrected distance visual acuity (UDVA), the analysis favored the MMC application with (MD -0.03, 95% CI: [-0.06, -0.00]; P = 0.05). There was no statistically significant increase in complications with MMC. In conclusion, MMC application after PRK is associated with a lower incidence of corneal haze formation with no statistically significant side effects. The long term effect can show improvement regarding UDVA favoring MMC. However, there is no significant effect of MMCs application regarding CDVA, and SE.     

Clinical implications of hepatic progenitor cell activation in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is one of the most prominent causes of liver-related morbidity in the Western world. NAFLD is a chronic disease charac...