Polyphenols Profile and Enzyme Inhibitory Properties of Blumea lacera (Burm. f.) DC.: A Potential Candidate against Obesity, Aging, and Skin Disorder.

Blumea lacera (Burm. f.) DC. is attracting scientific interest due to the diverse biological activities of its various parts and its use in folk medicine. The present study was undertaken to investigate the tissue-specific differential expression pattern of its total bioactive compounds. The study was further extended to whole plant phenolics profiling, in vitro enzyme inhibition activities, followed by in silico enzyme inhibition analysis to assess its potential as herbal medicine. The amount of total phenolics in different tissues was followed in decreasing order as old leaf, flower bud, root, young leaf, flower, old stem, and young stem, while that for the flavonoids was old leaf, root, young leaf, flower bud, flower, young stem, and old stem. This study identified rosmarinic acid, quercetin, and kaempferol in this plant for the first time. The solvent extracts demonstrated strong inhibition of lipase and tyrosinase activity, along with varying degrees of inhibition of acetylcholinesterase and butyrylcholinesterase activity. Among the detected compounds, ten displayed strong in silico binding affinities with the tested enzymes. The findings provide a new insight into further investigation of the medicinal potential of this species against obesity, neurological disorders, and aberrant skin color.

Burden of stroke in the Kingdom of Saudi Arabia: A soaring epidemic.

Stroke is a key cerebrovascular disease that is related to high morbidity and mortality in the globe. The Kingdom of Saudi Arabia (KSA) is not an exception where stroke is fast developing into a serious challenge due to the high mortality rate. Additionally, stroke presents a tremendous economic burden and has a devastating effect on the quality of lives of individuals. The number of stroke cases are increasing yearly, thus posing a major challenge to the health care system. Therefore, it is crucial to implement primary and secondary prevention strategies in the KSA. Nevertheless, as compared with developed countries, information on the prevalence, socio-demographic properties and prevention of stroke remains scarce that could be attributed to the shortage of research conducted in this specified region. The review is written to address the various aspects of stroke in the KSA, based on current literatures search using PubMed, Scopus, Web of Science and Google Scholar databases, to identify studies published since inception to Dec 2020.

Normalisation of human chorionic gonadotrophin (hCG) levels in a patient with partial molar pregnancy with a uterine mass without chemotherapy: impact of using herbal remedies.

OBJECTIVES: Level of ßhCG and the presence of any uterine mass of hydatidiform mole need a careful review or monitoring in order to prevent metastasis, provide an early treatment and avoid unnecessary chemotherapy. CASE PRESENTATION: A 36-year old fifth gravida patient who had a missed abortion was diagnosed as having a molar pregnancy with beta human chorionic gonadotrophin (ßhCG) level of 509,921 IU/L. Her lung field was clear and she underwent suction and curettage (S & C) procedure. However, after six weeks, AA presented to the emergency department with a massive bleeding, although her ßhCG level had decreased to 65,770 IU/L. A trans-abdominal ultrasound indicated the presence of an intra-uterine mass (3.0 × 4.4 cm). Nevertheless, her ßhCG continued to show a declining trend (8,426 IU/L). AA was advised to undergo a chemotherapy but she refused, citing preference for alternative medicine like herbs instead. She opted for an "at own risk" (AOR) discharge with scheduled follow up. Subsequently, her condition improved with her ßhCG showing a downward trend. Surprisingly, at six months post S & C, her ßhCG ameliorated to 0 IU/L with no mass detected by ultrasound. CONCLUSIONS: Brucea javanica fruits, Pereskia bleo and Annona muricata leaves can potentially be useful alternatives to chemotherapy and need further studies.

Prevalence, risk factors and clinical characteristics of respiratory syncytial virus-associated lower respiratory tract infections in Kelantan, Malaysia.

Respiratory syncytial virus (RSV) is a common pathogen affecting the respiratory tract in infants. To date, there is limited data on RSV occurrence in Malaysia especially in the northeast of Peninsular Malaysia which is significantly affected by the rainy (monsoon) season. This study aimed to determine the prevalence, risk factors (the presence of a male sibling and older school-age siblings, parental education level, monthly income, chronic lung disease, immunocompromised, being a passive smoker, multipara, breastfeeding, prematurity, congenital heart disease, nursery attendance, and rainy season) as well as clinical manifestations of RSV in hospitalized infants and children with lower respiratory tract infection (LRTI). Patients' nasopharyngeal aspirates were tested for RSV antigen, questionnaires, and seasonal variations were used to assess RSV infection. Approximately 22.6% of children were infected with RSV; mean age 7.68 ± 5.45 months. The peak incidence of RSV as a causative agent for LRTI in infants was less than or equal to 1-year old (83%) with approximately 50.5% of the affected children in the younger age group (6 months amd below). RSV infection was significantly but independently associated with the rainy season (odds ratio, 3.307; 95% confidence interval, 1.443-3.688; P < 0.001). The infection was also associated ( P < 0.05) with a higher number of severe clinical courses, poor feeding, vomiting, increased need for medical care and a shorter mean duration of symptoms before hospital admission. Our study suggested administration of the passive prophylaxis for RSV to high-risk infants during the rainy season in the months of October to January.

Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy.

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.

TRADITIONAL CARDIOVASCULAR RISK-FACTORS AMONG HEALTHCARE WORKERS IN KELANTAN, MALAYSIA.

We conducted a cross sectional study of cardiovascular risk factors among healthcare workers at four government hospitals in Kelantan, Malaysia. We randomly selected 330 subjects fulfilling the following study criteria: those who had been working for at least one year at that health facility, Malaysians citizens and those with some form of direct contact with patients. We conducted an interview, obtained physical measurements, a fasting blood sugar and fasting lipid profiles among 308 subjects. The mean age of the subjects was 43.5 years, 82% were female; 30.8%, 14.3%, 10.4%, 1.3% and 1.6% of the subjects had dyslipidemia, hypertension, diabetes mellitus, a history of stroke and a history of ischemic heart disease, respectively. Forty-two percent of subjects had at least one medical condition. The mean body mass index (BMI) was 27.0 kg/M2 (SD=4.8) and 24.3% had a BMI > or =30 kg/M2. The mean systolic and diastolic blood pressures were 121.5 mmHg (SD=14.0) and 76.5 mmHg (SD=9.7), respectively and the mean waist-hip ratio was 0.84 (SD=0.1). The mean fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein were 5.8 mmol/l (SD=2.4), 5.5 mmol/l (SD=1.0), 1.4 mmol/l (SD=0.9), 1.5 mmol/l (SD=0.3) and 3.5 mmol/l (SD=0.9), respectively. Our study population had a smaller proportion of hypertension than that of the general Malaysian population. They had higher fasting total cholesterol, slightly lower fasting blood sugar, with a large proportion of them, obese and had diabetes. Immediate intervention is needed to reduce the traditional cardiovascular risk factors in this population. Keywords: cardiovascular risk factors, health care workers, Malaysia

Therapeutic Interventions for the Suppression of Alzheimer's Disease: Quest for a Remedy.

Protein aggregation is facilitated by the generation of partially folded intermediates that lack most of the tertiary interactions, but retain the complete secondary structure. These partially folded states cross-link each other to form protein aggregates. Protein aggregates in an advanced stage result in the formation of amyloid fibrils, which have high tensile strength. These amyloid fibrils are associated with a number of pathologies, especially Alzheimer's disease, which involves the aggregation of the Aß peptide. In recent years, much attention has been paid to the generation of potent therapeutics to reduce Aß peptide fibrillation. This review summarizes the range of molecules used for this therapy, showing their potency against Aß amyloids, and suggests a positive future for the eradication of this dreaded disease.

Gene, ethnic and gender influences predisposition of adverse drug reactions to artesunate among Malaysians.

CONTEXT: Artesunate (AS) and amodiaquine (AQ) are two prodrugs widely used as antimalarial agents and are metabolized by the CYP P450 2A6 (CYP 2A6) and CYP P450 2C8 (CYP 2C8) enzymes, respectively. OBJECTIVE: In this study, we aim to investigate the association of both genes on AS and AQ's tolerabilities in the hope of identifying a pharmacogenetic approach that could be useful in prediction and prevention of adverse drug reactions (ADRs) among Malaysian population. MATERIALS AND METHODS: In this randomized crossover study, loose and AS/AQ formulations were administered to normal healthy volunteers (n = 24) over two study phases. The drugs' tolerabilities (incidence of facial flushing, giddiness, headache, nausea, abdominal discomfort, progression of liver enzymes and neutrophil counts) were compared between the two treatment arms. Volunteers were also genotyped for the CYP2C8 and CYP2A6 variants. RESULTS: The frequency of the CYP2A6*1B, CYP2A6*4, CYP2A6*8 and CYP2A6*9 alleles were 54.2%, 16.7%, 4.2% and 10.4%, respectively. No mutations for CYP2C8 gene were, however, detected. Most (96%) of the subjects were of the Malay ethnicity. Subjects having the CYP2A6*1B variants responsible for ultra rapid metabolism of AS suffered a significantly higher incidence of ADRs. DISCUSSION: Our study is the first to report that CYP2A6 genotyping influences AS's ADR. Gender also plays a role where females reported more incidences of nausea (p < 0.05). CONCLUSION: It is concluded that genetic polymorphisms of CYP2A6 as well as gender influence the side effect profiles of subjects receiving AS among this Malaysian population.

CYP3A4*18 polymorphisms and anti-hepatitis A virus seroprevalence.

BACKGROUND/AIMS: CYP3A4 is the major cytochrome in humans which shows reduced activity in chronic liver disease as well as in hepatic cirrhosis. The detection of this polymorphism may give an indication on the prognosis of patients having chronic viral hepatitis with superimposed hepatitis A infection. The aim of this study is to correlate the seroprevalence of anti-HAV antibodies in chronic liver disease patients having CYP3A4*18 polymorphisms. METHODOLOGY: This is a prospective study where patients (n=119) blood was tested for anti-HAVIgG and CYP3A4*18 polymorphism. RESULTS: The overall anti-HAV seroprevalence was 88.2%. The etiology of CLD was hepatitis B in 96 patients (80.7%) and hepatitis C in 23 patients (19.3%). There was a significant increase in the age of the prevalence of this disease after 30 years of age (p=0.008). CYP3A4*18 polymorphism was detected in 3 (2.5%) of the patients with chronic liver disease. However, there was no significant association between CP3A4*18 mutation and anti-HAV serology. CONCLUSIONS: Age was the most important factor in determining anti-HAV positivity. It is concluded that CYP3A4*18 genetic polymorphism does not play a main role in influencing the seroprevalence of anti-hepatitis A among chronic viral hepatitis B and C liver disease patients.