Determination toxic effects of Hystrix Brachyura Bezoar extracts using cancer cell lines and embryo zebrafish (Danio rerio) models and identification of active principles through GC-MS analysis

Ethnopharmacological relevance: Porcupine bezoar (PB) is used as folk medicine for various medical conditions including cancer treatment in Malaysia. However, its toxicity profile has never been thoroughly ascertained to confirm its safe nature as an efficacious traditional medicine in the treatment of cancer as well as other ailments. Aim of the study: This study was aimed to reveal three different PBs’ aqueous extracts(viz. PB-A, PB-B, PB-C) chemical constituent’s profile using GC-MS analysis, anticancer property on A375, HeLa and MCF7 cancer cells, toxicity profile on zebrafish embryo morphology, EC50, LC50 and teratogenicity index. Materials and methods: PBs’ extracts characterization was performed through GC-MS analysis, in vitro anticancer effect was carried out on A375, HeLa and MCF7 cancer cell lines and finally and toxicity properties on three different PBs aqueous extracts (viz. PB-A, PB-B, PB-C) were determined using zebrafish embryo model. Results: The GC-MS analysis revealed 10 similar compounds in all PBs’ extracts. Dilauryl thiodipropionate was found to be a major compound in all PBs’ extracts followed by tetradecanoic acid. An in vitro anticancer study revealed PB extracts exerted median inhibition concentration (IC50) <50 μg/mL, on cancer cells viz. A375, HeLa and MCF7 with no significant toxicity on normal cells viz. NHDF cells. In vivo toxicity of PBs extracts found affecting tail detachment, hatching, craniofacial, brain morphology, soft tissues, edema, spinal, somites, notochord and cardiovascular system (brachycardia, disruption of blood circulation) deformities. The LC50 and EC50 demonstrated PB extracts effect as dose and time dependent with median concentration <150.0 μg/mL. Additionally, teratogenicity index (TI) viz. >1.0 revealed teratogenic property for PB extracts. Conclusions: The findings revealed that all three PBs aqueous extracts possessed anticancer activity and exhibited significant toxicological effects on zebrafish embryos with high teratogenicity index. Hence, its use as an anticancer agent requires further investigation and medical attentions to determine its safe dose

State-level differentials in COVID-19 fatality: exploring age and sex disparities in Malaysia’s pandemic experience

Abstract Issue COVID-19 has resulted in mortality worldwide and exposed vulnerabilities in public health systems. Although countries have since transitioned to the endemic phase, it is nonetheless important to identify inequities within populations to improve public health strategies in light of another health crisis. Purpose This study aims to offer deeper insights into the sex and age differentials in COVID-19 fatality across different states in Malaysia, from the pandemic’s start to the country’s transition to the endemic phase. Methodology Analyses utilized data on the number of COVID-19 cases and deaths in Malaysia from January 2020 until April 2022. Case fatality rate (CFR) was computed for each state based on sex and age groups, for four periods (January–December 2020, January–June 2021, July–December 2021, and January–April 2022). Principal component analysis (PCA) uncovered patterns in the data and produced a multivariate visualization of the COVID-19 fatality within Malaysia. Findings Findings revealed heterogeneity in fatality and identified several vulnerable states, notably in the northern region (Kelantan, Perlis) and on the East Coast (Sabah, Sarawak). A sex disparity was apparent in Kelantan as the CFR among older females was higher than their male counterparts. Sabah exhibited relatively higher CFR among the child population from 2020 to 2021. Implication The findings deepened our understanding of COVID-19 fatality complexity, providing recommendations for Malaysia’s government in preparing for future health crises. Malaysia’s case study offers lessons on the need to address regional disparities and implement targeted strategies to protect vulnerable subgroups

Multivariate visualization of the global COVID-19 pandemic: A comparison of 161 countries.

BackgroundThe aim of the study was to visualize the global spread of the COVID-19 pandemic over the first 90 days, through the principal component analysis approach of dimensionality reduction.MethodsThis study used data from the Global COVID-19 Index provided by PEMANDU Associates. The sample, representing 161 countries, comprised the number of confirmed cases, deaths, stringency indices, population density and GNI per capita (USD). Correlation matrices were computed to reveal the association between the variables at three time points: day-30, day-60 and day-90. Three separate principal component analyses were computed for similar time points, and several standardized plots were produced.ResultsConfirmed cases and deaths due to COVID-19 showed positive but weak correlation with stringency and GNI per capita. Through principal component analysis, the first two principal components captured close to 70% of the variance of the data. The first component can be viewed as the severity of the COVID-19 surge in countries, whereas the second component largely corresponded to population density, followed by GNI per capita of countries. Multivariate visualization of the two dominating principal components provided a standardized comparison of the situation in the161 countries, performed on day-30, day-60 and day-90 since the first confirmed cases in countries worldwide.ConclusionVisualization of the global spread of COVID-19 showed the unequal severity of the pandemic across continents and over time. Distinct patterns in clusters of countries, which separated many European countries from those in Africa, suggested a contrast in terms of stringency measures and wealth of a country. The African continent appeared to fare better in terms of the COVID-19 pandemic and the burden of mortality in the first 90 days. A noticeable worsening trend was observed in several countries in the same relative time frame of the disease's first 90 days, especially in the United States of America

Effect of methanol extract of Dicranopteris linearis against carbon tetrachloride- induced acute liver injury in rats

Background: Dicranopteris linearis (family Gleicheniaceae) has been reported to possess anti-inflammatory and antioxidant activities but no attempt has been made to study its hepatoprotective potential. The aim of the present study was to determine the hepatoprotective effect of methanol extracts of D. linearis (MEDL) against carbon tetrachloride (CCl4)-induced acute liver injury in rats. Methods: 6 groups (n = 6) of rats received oral test solutions: 10% dimethyl sulfoxide (DMSO), 200 mg/kg silymarin, or MEDL (50, 250, and 500 mg/kg), once daily for 7 consecutive days, followed by hepatotoxicity induction with CCl4. Blood and liver were collected for biochemical and microscopic analysis. The extract was also subjected to antioxidant studies (e.g. 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging assays, oxygen radical absorbance capacity (ORAC) test and total phenolic content (TPC) determination), phytochemical screening and HPLC analysis. Results: Pretreatment with MEDL and silymarin significantly (P < 0.05) reduced the serum levels of AST, ALT and ALP, which were increased significantly (P < 0.05) in DMSO-pretreated group following treatment with CCl4. Histological analysis of liver tissues in groups pretreated with MEDL and silymarin showed mild necrosis and inflammation of the hepatocytes compared to the DMSO-pretreated group (negative control group). The MEDL showed higher DPPH- and superoxide anion-radical scavenging activity as well as high TPC and ORAC values indicating high antioxidant activity. Conclusions: MEDL exerts hepatoprotective activity that could be partly contributed by its antioxidant activity and high phenolic content, and hence demands further investigation

Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation

10.1186/s13059-021-02375-2GENOME BIOLOGY22

Major trends in the manifestations and treatment of rheumatoid arthritis in a multiethnic cohort in Singapore

10.1007/s00296-012-2602-2Rheumatology International3371693-1703RHIN

Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma

The genetics of renal cancer is dominated by inactivation of the VHL tumour suppressor gene in clear cell carcinoma (ccRCC), the commonest histological subtype. A recent large-scale screen of ~3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (also known as KDM6A), JARID1C (also known as KDM5C) and SETD2 (ref. 2). These genes encode enzymes that demethylate (UTX, JARID1C) or methylate (SETD2) key lysine residues of histone H3. Modification of the methylation state of these lysine residues of histone H3 regulates chromatin structure and is implicated in transcriptional control. However, together these mutations are present in fewer than 15% of ccRCC, suggesting the existence of additional, currently unidentified cancer genes. Here, we have sequenced the protein coding exome in a series of primary ccRCC and report the identification of the SWI/SNF chromatin remodelling complex gene PBRM1 (ref. 4) as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology