Genetic Spectrum of Familial Hypercholesterolaemia in the Malaysian Community: Identification of Pathogenic Gene Variants Using Targeted Next-Generation Sequencing.

Familial hypercholesterolaemia (FH) is caused by mutations in lipid metabolism genes, predominantly in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin-type 9 (PCSK9) and LDL receptor adaptor protein 1 (LDLRAP1). The prevalence of genetically confirmed FH and the detection rate of pathogenic variants (PV) amongst clinically diagnosed patients is not well established. Targeted next-generation sequencing of LDLR, APOB, PCSK9 and LDLRAP1 was performed on 372 clinically diagnosed Malaysian FH subjects. Out of 361 variants identified, 40 of them were PV (18 = LDLR, 15 = APOB, 5 = PCSK9 and 2 = LDLRAP1). The majority of the PV were LDLR and APOB, where the frequency of both PV were almost similar. About 39% of clinically diagnosed FH have PV in PCSK9 alone and two novel variants of PCSK9 were identified in this study, which have not been described in Malaysia and globally. The prevalence of genetically confirmed potential FH in the community was 1:427, with a detection rate of PV at 0.2% (12/5130). About one-fourth of clinically diagnosed FH in the Malaysian community can be genetically confirmed. The detection rate of genetic confirmation is similar between potential and possible FH groups, suggesting a need for genetic confirmation in index cases from both groups. Clinical and genetic confirmation of FH index cases in the community may enhance the early detection of affected family members through family cascade screening.

Are Vitamin E Supplementation Beneficial for Female Gynaecology Health and Diseases?

Vitamin E is known as an essential vitamin, and many studies had demonstrated the importance of vitamin E throughout the reproductive process, such as miscarriage, premature birth, preeclampsia, and intrauterine growth restriction, which could be caused by a lack of vitamin E during pregnancy. Its potent antioxidant properties can counteract the oxidative stress induced by oxygen free radicals and imbalance of oxidative-antioxidant levels, hence it may play a role in maintaining the normal function of the female reproductive system. Despite the fact that vitamin E is acknowledged as the substance needed for reproduction, its beneficial effects on female fertility, gynaecological health, and diseases are still poorly understood and lacking. Therefore, the goal of this paper is to provide a summary of the known roles of vitamin E supplementation in women for gynaecological health and reproductive-related diseases, as well as its future perspective.

Ursodeoxycholic acid protects cardiomyocytes against cobalt chloride induced hypoxia by regulating transcriptional mediator of cells stress hypoxia inducible factor 1α and p53 protein.

In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca2+ ]i ), and sphingosine-1-phosphate (S1P)-receptor via Gαi -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca2+ ]i , and S1P-Gαi -coupled-receptor. Cardiomyocytes were isolated from newborn rats (0-2 days), and hypoxia was induced by using cobalt chloride (CoCl2 ). Cardiomyocytes were treated with UDCA and cotreated with either FTY720 (S1P-receptor agonist) or pertussis toxin (PTX; Gαi inhibitor). Cells were subjected for proliferation assay, beating frequency, QuantiGene Plex assay, western blot, immunofluorescence, and calcium imaging. Our findings showed that UDCA counteracted the effects of CoCl2 on cell viability, beating frequency, HIF-1α, and p53 protein expression. We found that these cardioprotection effects of UDCA were similar to FTY720, S1P agonist. Furthermore, we observed that UDCA protects CMs against CoCl2 -induced [Ca2+ ]i dynamic alteration. Pharmacological inhibition of the Gαi -sensitive receptor did not abolish the cardioprotection of UDCA against CoCl2 detrimental effects, except for cell viability and [Ca2+ ]i . Pertussis toxin is partially effective in inhibiting UDCA protection against CoCl2 effects on CM cell viability. Interestingly, PTX fully inhibits UDCA cardioprotection on CoCl2 -induced [Ca2+ ]i dynamic changes. We conclude that UDCA cardioprotection against CoCl2 -induced hypoxia is similar to FTY720, and its actions are not fully mediated by the Gαi -coupled protein sensitive pathways. Ursodeoxycholic acid is the most hydrophilic bile acid and is currently used to treat liver diseases. Recently, UDCA is shown to have a cardioprotection effects; however, the mechanism of UDCA cardioprotection is still poorly understood. The current data generated were the first to show that UDCA is able to inhibit the activation of HIF-1α and p53 protein during CoCl2 -induced hypoxia in cardiomyocytes. This study provides an insight of UDCA mechanism in protecting cardiomyocytes against hypoxia.

Establishment of Reference Intervals of Blood Parameters Among the Healthy Afghan Population.

Purpose: This study was designed and conducted to validate the reference values of hematological parameters for healthy adult male and female residents of Kabul city, Afghanistan. Methodology: In this cross-sectional study, the samples were collected according to a non-random sampling method. Blood samples were collected from students and employees of Kabul University. The study included 166 males and 125 females, aged 18-45 years. The selection and exclusion of participants were carried out according to a questionnaire and the assessment of serum ferritin and vitamin B12 levels. Candidates with lower serum ferritin and vitamin B12, a history of chronic disease, females with menstruation or pregnancy, and those with chronic abdominal pain were excluded. Results: Reference ranges for all blood parameters were determined by a non-parametric method. The determined reference values were compared between males and females by the Z-test. Reference intervals for hemoglobin (4.5-6.3 g/dL for males and 3.66-5.67 g/dL for females) and hematocrit (36.23-55.93% for males and 30.20-53.86% for females) were significantly (p<0.05) higher in males. No significant (p<0.05) differences were observed between the reference intervals for the red blood cell count. Conclusion: Therefore, we conclude that the commonly used reference intervals should be revised for the Afghan population, as our findings indicated higher reference values for the hemoglobin and hematocrit indices.

Palm-based tocotrienol-rich fraction (TRF) supplementation modulates cardiac sod1 expression, fxr target gene expression, and tauro-conjugated bile acid levels in aleptinemic mice fed a high-fat diet.

Tocotrienol-rich fraction (TRF) has been reported to protect the heart from oxidative stress-induced inflammation. It is, however, unclear whether the protective effects of TRF against oxidative stress involve the activation of farnesoid X receptor (fxr), a bile acid receptor, and the regulation of bile acid metabolites. In the current study, we investigated the effects of TRF supplementation on antioxidant activities, expression of fxr and its target genes in cardiac tissue, and serum untargeted metabolomics of high-fat diet-fed mice. Mice were divided into high-fat diet (HFD) with or without TRF supplementation (control) for 6 weeks. At the end of the intervention, body weight (BW), waist circumference (WC), and random blood glucose were measured. Heart tissues were collected, and the gene expression of sod1, sod2, gpx, and fxr and its target genes shp and stat3 was determined. Serum was subjected to untargeted metabolomic analysis using UHPLC-Orbitrap. In comparison to the control, the WC of the TRF-treated group was higher (p >0.05) than that of the HFD-only group, in addition there was no significant difference in weight or random blood glucose level. Downregulation of sod1, sod2, and gpx expression was observed in TRF-treated mice; however, only sod1 was significant when compared to the HFD only group. The expression of cardiac shp (fxr target gene) was significantly upregulated, but stat3 was significantly downregulated in the TRF-treated group compared to the HFD-only group. Biochemical pathways found to be influenced by TRF supplementation include bile acid secretion, primary bile acid biosynthesis, and biotin and cholesterol metabolism. In conclusion, TRF supplementation in HFD-fed mice affects antioxidant activities, and more interestingly, TRF also acts as a signaling molecule that is possibly involved in several bile acid-related biochemical pathways accompanied by an increase in cardiac fxr shp expression. This study provides new insight into TRF in deregulating bile acid receptors and metabolites in high-fat diet-fed mice.

Hydroxychavicol as a potential anticancer agent (Review).

Piper betle leaves are widely cultivated in Malaysia, India, Indonesia and Thailand. They have been used as a traditional medicine for centuries due to their medicinal properties, including antioxidant, antiproliferative, antibacterial, antifungal and anti-inflammatory properties, which are attributable to their high phenolic contents. Hydroxychavicol (HC), a primary constituent of P. betle leaves, is known to possess antiproliferative activity at micromolar doses on various cancer cell lines of different origins while leaving normal cells unharmed. The present review summarises the mechanisms of action of HC reported in the literature, reviews the scope of work done thus far and outlines the direction of future research on the potential of HC as an anticancer agent. PubMed, Scopus and Web of Science were searched using the keywords (hydroxychavicol OR 4-allylpyrocatechol OR 4-allylcatechol) AND (cancer OR carcinogenesis OR tumour OR carcinoma) to acquire research articles. In vitro studies reported several possible mechanisms for the chemopreventive effects of HC against cancer cell lines, including chronic myelogenous leukaemia (CML), prostate, glioma, breast and colorectal cancers, while in vivo studies encompassed investigations on Ehrlich ascites carcinoma cells in Swiss albino mice and a CML mouse model. These studies suggest that HC exerts its anticancer effect via the modulation of mitochondrial membrane potential and the c-Jun N-terminal kinase, mitogen-activated protein kinase and endoplasmic reticulum-unfolded protein responses pathways and the generation of reactive oxygen species. In summary, future research should focus on combinations of HC with other anticancer drugs and testing in animal models to evaluate its bioavailability, potency and tissue and dose selectivity.

The effects of trans fat diet intake on metabolic parameters and pancreatic tissue in offspring of prenatal bisphenol A exposed rats.

Bisphenol A (BPA) is a plasticiser used in the manufacturing of many products and its effects on human health remain controversial. Up till now, BPA involvement in metabolic syndrome risk and development is still not fully understood. In this study, we aimed to investigate the effect of prenatal BPA exposure with postnatal trans-fat diet intake on metabolic parameters and pancreatic tissue histology. Eighteen pregnant rats were divided into control (CTL), vehicle tween 80 (VHC), and BPA (5 mg/kg/day) from gestational day (GD) 2 until GD 21, then their weaning rat's offspring were fed with normal diet (ND) or trans-fat diet (TFD) from postnatal week (PNW) 3 until PNW 14. The rats were then sacrificed and the blood (biochemical analysis) and pancreatic tissues (histological analysis) were collected. Glucose, insulin, and lipid profile were measured. The study has shown that there was no significant difference between groups with regard to glucose, insulin, and lipid profiles (p > 0.05). All pancreatic tissues showed normal architecture with irregular islets of Langerhans in TFD intake groups compared to offspring that consumed ND. Furthermore, the pancreatic histomorphometry was also affected whereby the study findings revealed that there was a significant increase in the mean number of pancreatic islets in rats from BPA-TFD group (5.987 ± 0.3159 islets/field, p = 0.0022) compared to those fed with ND and BPA non-exposed. In addition, the results have found that prenatal BPA exposure resulted in a significant decrease in the pancreatic islets diameter of the BPA-ND group (183.3 ± 23.28 µm, p = 0.0022) compared to all other groups. In conclusion, prenatal BPA exposure with postnatal TFD in the offspring may affect glucose homeostasis and pancreatic islets in adulthood, and the effect may be more aggravated in late adulthood.

Hybrid Inorganic Organic PSF/Hap Dual-Layer Hollow Fibre Membrane for the Treatment of Lead Contaminated Water.

Lead (Pb) exposure can be harmful to public health, especially through drinking water. One of the promising treatment methods for lead contaminated water is the adsorption-filtration method. To ensure the cost-effectiveness of the process, naturally derived adsorbent shall be utilised. In this study, hydroxyapatite particles, Ca10(PO4)6(OH)2 (HAP) derived from waste cockle shell, were incorporated into the outer layer of polysulfone/HAP (PSf/HAP) dual-layer hollow fibre (DLHF) membrane to enhance the removal of lead from the water source due to its hydrophilic nature and excellent adsorption capacity. The PSf/HAP DLHF membranes at different HAP loadings in the outer layer (0, 10, 20, 30 and 40 wt%) were fabricated via the co-extrusion phase inversion technique. The performance of the DLHF membranes was evaluated in terms of pure water flux, permeability and adsorption capacity towards lead. The results indicated that the HAP was successfully incorporated into the outer layer of the membrane, as visibly confirmed by microscopic analysis. The trend was towards an increase in pure water flux, permeability and lead adsorption capacity as the HAP loading increased to the optimum loading of 30 wt%. The optimized DLHF membrane displayed a reduced water contact angle by 95%, indicating its improved surface hydrophilicity, which positively affects the pure water flux and permeability of the membrane. Furthermore, the DLHF membrane possessed the highest lead adsorption capacity, 141.2 mg/g. The development of a hybrid inorganic-organic DLHF membrane via the incorporation of the naturally derived HAP in the outer layer is a cost-effective approach to treat lead contaminated water.

Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study.

BACKGROUND: Familial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor adaptor protein 1 (LDLRAP1). It is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels leading to premature coronary artery disease. FH can be clinically diagnosed using established clinical criteria, namely, Simon Broome (SB) and Dutch Lipid Clinic Criteria (DLCC), and can be identified using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT), a primary care screening tool. OBJECTIVE: This study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting. METHODS: This is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the "think-aloud" methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool. RESULTS: The recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023. CONCLUSIONS: This study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients' perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47911.

Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care.

BACKGROUND In Malaysia, the prevalence of genetically confirmed heterozygous familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care. CASE REPORT In this case series, we report 3 FH cases detected in primary care due to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein-B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest LDL-c level, 8.6 mmol/L, and prominent tendon xanthomas. In case 2, the patient had an LDL-c level of 5.7 mmol/L and premature corneal arcus. In case 3, the patient had an LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with statins and therapeutic lifestyle modifications. They were referred to the lipid specialists for up-titration of lipid lowering medications. First-degree relatives were identified and referred for cascade testing. CONCLUSIONS This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with lipid specialists.

The Current Findings on the Impact of Prenatal BPA Exposure on Metabolic Parameters: In Vivo and Epidemiological Evidence.

Metabolic syndrome (MS) is a multifactorial disease entity and is not fully understood. Growing evidence suggests that early exposure to bisphenol A (BPA) is a significant risk factor for the development of metabolic diseases. BPA is a monomer used in the manufacturing of polycarbonate plastics, thermal receipt paper, and epoxy resins. Owing to its widespread use, BPA has been detected in human fluids and tissues, including blood, placental breast milk, and follicular fluid. In the present review, we aimed to review the impact of prenatal exposure to different doses of BPA on metabolic parameters as determined by in vivo and epidemiological studies. The PubMed, Scopus, and Web of Science electronic databases were searched to identify articles published during a period of 15 years from 2006 to 2021, and 29 studies met the criteria. Most studies demonstrated that prenatal exposure to low BPA concentrations correlated with alterations in metabolic parameters in childhood and an increased risk of metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM), in adulthood. Therefore, prenatal exposure to low doses of BPA may be associated with an increased risk of obesity and T2DM in a sex-specific manner.

The Effect of Irradiated Riboflavin in Human Tenon's Fibroblast - A Study on Cellular Viability.

PURPOSE/ AIM: The main purpose of this work is to study the cellular viability effect of irradiated riboflavin in cultured human tenon fibroblasts. MATERIALS AND METHODS: The tenon tissue was harvested from a patient undergoing strabismus surgery. The human tenon fibroblast cell culture and isolation were performed according to the standard laboratory cell culturing protocol. The cells were divided into three groups: control, treatment with irradiated and non-irradiated riboflavin. There were five different concentrations (0.00156%, 0.003125%, 0.00625%, 0.0125%, 0.025%) in each group of riboflavin. The fibroblasts were treated with riboflavin and the cellular viability was assessed at 24-hour and 48-hour post treatment with MTT 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide colorimetric assay. The absorbance values were analysed using Magellan microplate reader data analysis. A triplicate of readings was taken. The data were presented as mean ± standard deviation of the triplicates. Statistical analysis was performed with Statistical Package for Social Sciences (SPSS) analysis version 23. RESULTS: Irradiated riboflavin caused a concentration-dependent cell death in human tenon fibroblast cell culture (p < .05). The antiproliferative difference between irradiated and non-irradiated riboflavin was significant up to 48 hours (p < .05). Post hoc multiple comparisons showed higher concentrations of irradiated riboflavin (0.0125% and 0.025%) caused more reduction in cellular viability in human tenon fibroblast cells (p < .05). The duration of treatment is not a causative factor in this study. CONCLUSIONS: This pilot experiment demonstrated that irradiated riboflavin induced cell death in human tenon fibroblast culture in a concentration-dependent manner, but is not time-dependent. Further exploratory investigations should be performed to determine the mechanism of cell death. We postulate that apoptosis occurred in these irradiated riboflavin-treated cells.

A Review of Polychlorinated Biphenyls (PCBs) Pollution in the Air: Where and How Much Are We Exposed to?

Polychlorinated biphenyls (PCBs) were widely used in industrial and commercial applications, until they were banned in the late 1970s as a result of their significant environmental pollution. PCBs in the environment gained scientific interest because of their persistence and the potential threats they pose to humans. Traditionally, human exposure to PCBs was linked to dietary ingestion. Inhalational exposure to these contaminants is often overlooked. This review discusses the occurrence and distribution of PCBs in environmental matrices and their associated health impacts. Severe PCB contamination levels have been reported in e-waste recycling areas. The occurrence of high PCB levels, notably in urban and industrial areas, might result from extensive PCB use and intensive human activity. Furthermore, PCB contamination in the indoor environment is ten-fold higher than outdoors, which may present expose risk for humans through the inhalation of contaminated air or through the ingestion of dust. In such settings, the inhalation route may contribute significantly to PCB exposure. The data on human health effects due to PCB inhalation are scarce. More epidemiological studies should be performed to investigate the inhalation dose and response mechanism and to evaluate the health risks. Further studies should also evaluate the health impact of prolonged low-concentration PCB exposure.

Prenatal Bisphenol a Exposure and Postnatal Trans Fat Diet Alter Small Intestinal Morphology and Its Global DNA Methylation in Male Sprague-Dawley Rats, Leading to Obesity Development.

In this study, we aimed to determine whether a postnatal trans fat diet (TFD) could aggravate prenatal bisphenol A (BPA) exposure effects on offspring's small intestine and adulthood obesity, due to the relatively sparse findings on how the interaction between these two variables interrupt the small intestinal cells. Twelve pregnant rats were administered with either unspiked drinking water (control; CTL) or BPA-spiked drinking water throughout pregnancy. Twelve weaned pups from each pregnancy group were then given either a normal diet (ND) or TFD from postnatal week (PNW) 3 until PNW14, divided into control offspring on normal diet (CTL-ND), BPA-exposed offspring on normal diet (BPA-ND), control offspring on trans fat diet (CTL-TFD), and BPA offspring on trans fat diet (BPA-TFD) groups. Body weight (BW), waist circumference, and food and water intake were measured weekly in offspring. At PNW14, small intestines were collected for global DNA methylation and histological analyses. Marked differences in BW were observed starting at PNW9 in BPA-TFD (389.5 ± 10.0 g; p < 0.05) relative to CTL-ND (339.0 ± 7.2 g), which persisted until PNW13 (505.0 ± 15.6 g). In contrast, water and food intake between offspring were significantly different (p < 0.01−0.05) at earlier ages only (PNW4−6 and PNW7−9, respectively). Furthermore, substantial differences in the general parameters of the intestinal structures were exclusive to ileum crypt length alone, whereby both BPA-ND (150.5 ± 5.1 µm; p < 0.001), and BPA-TFD (130.3 ± 9.9 µm; p < 0.05) were significantly longer than CTL-ND (96.8 ± 8.9 µm). Moreover, BPA-ND (2.898 ± 0.147%; p < 0.05) demonstrated global small intestinal hypermethylation when compared to CTL-ND and CTL-TFD (1.973 ± 0.232% and 1.913 ± 0.256%, respectively). Prenatal BPA exposure may significantly affect offspring's physiological parameters and intestinal function. Additionally, our data suggest that there might be compensatory responses to postnatal TFD in the combined BPA prenatal group (BPA-TFD).

The Effect of BPA-Treated Water on the Small Intestine via an In Vivo Study.

Since the major route of BPA exposure is via the oral route, BPA may have effects on the gastrointestinal tract, especially on the intestinal barrier, where most digestion and absorption processes occur. In this study, the effects of BPA-treated water on the small intestine (SI) and SI tight junction proteins (TJPs) of both pregnant Sprague-Dawley rats and their fetuses were investigated. Previously, hybrid photocatalytic filtration treatment by a visible light driven N-doped TiO2 membrane has successfully removed up to 81.6% of BPA in water. The effect of BPA-untreated (5.00 ± ppm) and BPA-treated water (0.9 ± ppm) after 21 days of exposure on the jejunum and ileum, as well as the expressions of claudin proteins, were investigated by Western blotting (WB) and hematoxylin and eosin (H&E) in order to investigate the potential of the photocatalytic membrane in removing the detrimental effect of BPA. The results suggest that BPA exposure altered the morphology of villi, and affected the expression level of claudin-2, -3, and -4 proteins in the jejunum and ileum of both pregnant rats and their fetuses. Interestingly, villi and claudins expressions were undisrupted in a treated-BPA water group, which indicated that the degradation of BPA via membranes effectively mitigates the effect on BPA on gastrointestinal tract.

Polyvinylidene Difluoride (PVDF) Hollow Fiber Membrane Incorporated with Antibacterial and Anti-Fouling by Zinc Oxide for Water and Wastewater Treatment.

The addition of antibacterial material to hollow fiber membranes improves the membrane anti-biofouling characteristics. Antibacterial membranes were fabricated in this study to improve membrane function while also extending membrane lifetime. Neat polyvinylidene difluoride (PVDF) and PVDF hollow fiber membrane with the incorporation of antibacterial agent zinc oxide (ZnO) nanoparticles with various loading (2.5-7.5 wt.%) were fabricated by using dry/wet spinning method. The membrane structure, particle distribution, functional group, hydrophilicity, and pore size of each membrane were all assessed. The result shows that all ZnO/PVDF hollow fiber membranes have the asymmetric structure with even dispersion of ZnO nanoparticles throughout the membranes. The results showed that increased ZnO loadings considerably improved membrane hydrophilicity, and average pore size, in addition to good performance of pure water flux. Antibacterial testing shows that ZnO incorporated in the membrane matrix and membrane surfaces prevents bacteria that cause biofouling from adhering to the membrane. ZnO/PVDF membrane recorded excellent bovine serum albumin (BSA) rejection at 93.4% ± 0.4 with flux recovery rate at 70.9% ± 2.1. These results suggest that antibacterial ZnO/PVDF hollow fiber membranes are promising in relation to reducing biofouling for various water and wastewater treatment.

Palm tocotrienol rich fraction with palm kernel oil supplementation prevents development of liver steatosis in high fat diet ICR mice.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in Asian countries is increasing at concerning level. Currently, no specific treatment available to prevent its oxidative stress and progression except for diet and lifestyle changes. Vitamin E such as tocotrienol-rich fraction (TRF) has a promising potential in preventing NAFLD progression. TRF is a potent antioxidant but has low bioavailability due to the use of long-chain triglycerides (LCT) as its carrier. Testing of potential therapeutic agents such as TRF are commonly carried out using animal models. These animal models are often costly due to limited access to the supply especially Asian countries and predisposed to high transportation cost. Lower expenditure of NAFLD model should be investigated without forfeiting the outcome of study. Therefore, this study addresses the gap by utilizing the ICR mice as NAFLD model through dietary modification and testing on the newly formulated TRF with combination of palm kernel oil (PKO) as a medium-chain triglycerides (MCT) carrier. METHODS: Fifteen ICR strain mice were randomly group into two control and one treatment group. Control groups received high-fat diet (HFD) only and standard diet while treatment group was given HFD with TRF (200 mg/kg/day). Study was carried out for 10 weeks. Weights were recorded twice a week. At the end of study, all mice were euthanized and data such weights, waist circumference and random blood glucose were recorded. Liver from each mouse were prepared for histology assessment. RESULTS: Mice mean weights and random blood sugar showed no difference between group (P>0.05) while significance waist circumference was larger in HFD and TRF groups compared to SD (P<0.05). Histology assessment showed steatosis in TRF group had lower severity compared to HFD group. NAFLD activity score (NAS) was lower in treatment group compared to HFD group. CONCLUSIONS: TRF showed promising potential as an agent to reduce NAFLD progression in ICR mice. Further study at gene and protein levels are required to fully elucidate the mechanism of this new TRF formulation in reducing NAFLD progression.

Immobilization techniques of a photocatalyst into and onto a polymer membrane for photocatalytic activity.

This article reviews the various techniques of immobilizing a photocatalyst into and onto the polymer membrane for pollutant removal and as a problem solver in handling suspended photocatalyst issues from the previous literature. A particular focus is given to the preparation of mixed matrix membranes and deposition techniques for photocatalytic degradation in applications for wastewater treatment. Advantages and disadvantages in this application are evaluated. Various operating conditions during the process are presented. About 90 recently published studies (2008-2020) are reviewed. From the literature, it was found that TiO2 is the most favoured photocatalyst that is frequently used in photocatalytic water treatment. Dry-wet co-spinning and sputtering techniques emerged as the promising technique for immobilizing a uniformly distributed photocatalyst within the polymeric membrane, and exhibited excellence pollutant removal. In general, the technical applicability is the key factor in selecting the best photocatalyst immobilizing technique for water treatment. Finally, the scope of various techniques that have been reviewed may provide potential for future photocatalytic study.

Understanding the Impact of Perfluorinated Compounds on Cardiovascular Diseases and Their Risk Factors: A Meta-Analysis Study.

Perfluorinated compounds (PFCs) are non-biodegradable synthetic chemical compounds that are widely used in manufacturing many household products. Many studies have reported the association between PFCs exposure with the risk of developing cardiovascular diseases (CVDs). However, those reports are still debatable, due to their findings. Thus, this review paper aimed to analyse the association of PFCs compound with CVDs and their risk factors in humans by systematic review and meta-analysis. Google Scholar, PubMed and ScienceDirect were searched for PFCs studies on CVDs and their risk from 2009 until present. The association of PFCs exposure with the prevalence of CVDs and their risk factors were assessed by calculating the quality criteria, odds ratios (ORs), and 95% confidence intervals (CIs). CVDs risk factors were divided into serum lipid profile (main risk factor) and other known risk factors. The meta-analysis was then used to derive a combined OR test for heterogeneity in findings between studies. Twenty-nine articles were included. Our meta-analysis indicated that PFCs exposure could be associated with CVDs (Test for overall effect: z = 2.2, p = 0.02; Test for heterogeneity: I2 = 91.6%, CI = 0.92-1.58, p < 0.0001) and their risk factors (Test for overall effect: z = 4.03, p < 0.0001; Test for heterogeneity: I2 = 85.8%, CI = 1.00-1.14, p < 0.0001). In serum lipids, total cholesterol levels are frequently reported associated with the exposure of PFCs. Among PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) exposure increased the risk of CVDs than other types of PFCs. Although the risk of PFOA and PFOS were positively associated with CVDs and their risk factors, more observational studies shall be carried out to identify the long-term effects of these contaminants in premature CVDs development in patients.

Untargeted serum metabolites profiling in high-fat diet mice supplemented with enhanced palm tocotrienol-rich fraction using UHPLC-MS.

Excessive high fat dietary intake promotes risk of developing non-alcoholic fatty liver disease (NAFLD) and predisposed with oxidative stress. Palm based tocotrienol-rich fraction (TRF) has been reported able to ameliorate oxidative stress but exhibited poor bioavailability. Thus, we investigated whether an enhanced formulation of TRF in combination with palm kernel oil (medium-chain triglycerides) (ETRF) could ameliorate the effect of high-fat diet (HFD) on leptin-deficient male mice. All the animals were divided into HFD only (HFD group), HFD supplemented with ETRF (ETRF group) and HFD supplemented with TRF (TRF group) and HFD supplemented with PKO (PKO group). After 6 weeks, sera were collected for untargeted metabolite profiling using UHPLC-Orbitrap MS. Univariate analysis unveiled alternation in metabolites for bile acids, amino acids, fatty acids, sphingolipids, and alkaloids. Bile acids, lysine, arachidonic acid, and sphingolipids were downregulated while xanthine and hypoxanthine were upregulated in TRF and ETRF group. The regulation of these metabolites suggests that ETRF may promote better fatty acid oxidation, reduce oxidative stress and pro-inflammatory metabolites and acts as anti-inflammatory in fatty liver compared to TRF. Metabolites regulated by ETRF also provide insight of its role in fatty liver. However, further investigation is warranted to identify the mechanisms involved.