Polymorphisms in P53 and VEGFA genes in different subtypes of periorbital hyperpigmentation in a Malaysian Chinese population.

BACKGROUND/OBJECTIVES: The unknown pathogenesis of periorbital hyperpigmentation makes its treatment difficult. Existing evidence links p53 and VEGFA genes with skin hyperpigmentation. This study was aimed at (i) identifying the clinical pattern of periorbital hyperpigmentation; and (ii) detecting the presence of VEGFA and P53 single nucleotide polymorphism (SNPs) in different subtypes of periorbital hyperpigmentation in Malaysian Chinese. METHODS: A cross-sectional study was conducted among Malaysian Chinese. Clinical assessments were performed, and medical history was collected. Three regions of p53 and two of VEGFA were amplified by PCR followed by direct sequencing using saliva-extracted DNA. RESULTS: Eighty-four participants were recruited (average age 22.2 years). In the majority (n = 62), both eyelids were affected. Facial pigmentary, demarcation lines, tear trough and eye bags were not observed. Mixed (pigmented-vascular) was the most common subtype. Thirteen SNPs were found, nine of which are new. Only three out of 13 SNPs showed significant association with periorbital hyperpigmentation presentation. TA genotype in rs1437756379 (p53) was significantly more prevalent among participants with mixed subtype (P = 0.011) while AC genotype in rs1377053612 (VEGFA) was significantly more prevalent among pigmented subtype (P = 0.028). AA genotype in rs1479430148 (VEGFA) was significantly associated with allergic rhinitis in mixed subtype (P = 0.012). CONCLUSION: Mixed subtype was the most prevalent type of periorbital hyperpigmentation in the study population. Three polymorphisms in p53 and VEGFA genes were statistically linked with different clinical presentations of periorbital hyperpigmentation.

Effectiveness and relevant factors of platelet-rich plasma treatment in managing plantar fasciitis: A systematic review.

BACKGROUND: Plantar fasciitis (PF) is a common foot complaint, affects both active sportsmen and physically inactive middle age group. It is believed that PF results from degenerative changes rather than inflammation. Platelet-rich plasma (PRP) therapy has been introduced as an alternative therapy for PF. This study is aimed to systematically review to the effectiveness and relevant factors of PRP treatment in managing PF. MATERIALS AND METHODS: A search was conducted in electronic databases, including PubMed, Scopus, and Google Scholar using different keywords. Publications in English-language from 2010 to 2015 were included. Two reviewers extracted data from selected articles after the quality assessment was done. RESULTS: A total of 1126 articles were retrieved, but only 12 articles met inclusion and exclusion criteria. With a total of 455 patients, a number of potentially influencing factors on the effectiveness of PRP for PF was identified. In all these studies, PRP had been injected directly into the plantar fascia, with or without ultrasound guidance. Steps from preparation to injection were found equally crucial. Amount of collected blood, types of blood anti-coagulant, methods in preparing PRP, speed, and numbers of time the blood samples were centrifuged, activating agent added to the PRP and techniques of injection, were varied between different studies. Regardless of these variations, superiority of PRP treatment compared to steroid was reported in all studies. CONCLUSION: In conclusion, PRP therapy might provide an effective alternative to conservative management of PF with no obvious side effect or complication. The onset of action after PRP injection also greatly depended on the degree of degeneration.

Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy.

Colorectal cancer is one of the commonest cancers in the world and it is also a common cause of cancer-related death worldwide. Despite advanced treatment strategies, the disease is rarely cured completely due to recurrence. Evidence shows that this is due to a small population of cells, called cancer stem cells (CSCs), in the tumour mass that have the self-renewal and differentiation potential to give rise to a new tumour population. Many pre-clinical and clinical studies have used curcumin and its analogues as anti-cancer agents in various types of cancer, including colorectal cancer. Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth. In this review, we highlight the efficacy of curcumin and its analogues in targeting colorectal CSC and also the underlying molecular mechanism involved. Curcumin, in the presence or absence of other anti-cancer agents, has been shown to reduce the size of tumour mass and growth in both in vivo and in vitro studies by affecting many intracellular events that are associated with cancer progression and CSC formation. An insight into the molecular mechanism has unraveled the mode of action via which curcumin could affect the key regulators in CSC, importantly; (1) the signaling pathways, including Wnt/ß-catenin, Sonic Hedgehog, Notch and PI3K/Akt/mTOR, (2) microRNA and (3) the epithelial-mesenchymal transition at multiple levels. Therefore, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy, therefore, combination therapy using anti-cancer agent with curcumin could be much more effective than treatment using a single cancer agent. This potential treatment modality can be further developed by employing an effective delivery system using a nanotechnology based approach to treat colorectal cancer.

3'-UTR variations and G6PD deficiency.

The combination of two silent mutations, c.1311C>T in exon 11 and IVS11 T93C (glucose-6-phosphate dehydrogenase (G6PD) 1311T/93C), with unknown mechanism, have been reported in G6PD-deficient individuals in Asian populations including Malaysian aboriginal group, Negrito. Here, we report the screening of G6PD gene in 103 Negrito volunteers using denaturing high-performance liquid chromatography (dHPLC) and direct sequencing. A total of 48 individuals (46.6%) were G6PD deficient, 83.3% of these carried G6PD 1311T/93C with enzyme activity ranging from 1.8 to 4.8 U gHb(-1). Three novel single-nucleotide polymorphisms (SNPs), rs112950723, rs111485003 and rs1050757, were found in the G6PD 3'-untranslated region (UTR). Strong association was observed between haplotype 1311T/93C and rs1050757G, which is located inside the 35 bp AG-rich region. In silico analysis revealed that the transition of A to G at position rs1050757 makes significant changes in the G6PD mRNA secondary structure. Moreover, putative micro (mi)RNA target sites were identified in 3'-UTR of G6PD gene, two of these in the region encompassing rs1050757. It could be speculated that rs1050757 have a potential functional effect on the downregulation of mRNA and consequently G6PD deficiency either by affecting mRNA stability and translation or mirRNA regulation process. This is the first report of biochemical association of an SNP in 3'-UTR of G6PD gene and the possible role of mRNA secondary structure.

Mental Health and the COVID-19 Pandemic: Observational Evidence from Malaysia.

The interplay of physical, social, and economic factors during the pandemic adversely affected the mental health of healthy people and exacerbated pre-existing mental disorders. This study aimed to determine the impact of the COVID-19 pandemic on the mental health of the general population in Malaysia. A cross-sectional study involving 1246 participants was conducted. A validated questionnaire consisting of the level of knowledge and practice of precautionary behaviors, the Depression, Anxiety, and Stress Scales (DASS), and the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF) was used as an instrument to assess the impacts of the COVID-19 pandemic. Results revealed that most participants possessed a high level of knowledge about COVID-19 and practiced wearing face masks daily as a precautionary measure. The average DASS scores were beyond the mild to moderate cut-off point for all three domains. The present study found that prolonged lockdowns had significantly impacted (p < 0.05), the mental health of the general population in Malaysia, reducing quality of life during the pandemic. Employment status, financial instability, and low annual incomes appeared to be risk factors (p < 0.05) contributing to mental distress, while older age played a protective role (p < 0.05). This is the first large-scale study in Malaysia to assess the impacts of the COVID-19 pandemic on the general population.

Dietary protein interacts with polygenic risk scores and modulates serum concentrations of C-reactive protein in overweight and obese Malaysian adults.

Dietary intake may interact with gene variants and modulate inflammatory status. This study aimed to investigate the combined effect of fat mass and obesity-associated rs9930501, rs9930506, and rs9932754 and beta-2 adrenergic receptor rs1042713 on C-reactive protein (CRP) concentrations using polygenic risk scores (PRS), and modulatory effect of dietary nutrients on these associations. We hypothesized that higher protein intake is associated with lower inflammatory status in individuals genetically predisposed to obesity. PRS was computed as the weighted sum of the risk alleles possessed and stratified into first (0-0.64), second (0.65-3.59), and third (3.60-8.18) tertiles. A total of 128 overweight and obese Malaysian adults were dichotomized into groups of low and elevated inflammatory status (CRP concentrations ≤3 and >3 mg/L, respectively). One-half of the study participants (51%) were found to have elevated inflammatory status. Second- and third-tertile PRS were significantly associated with increased odds of elevated inflammatory status, 7.56 (95% confidence interval [CI], 1.98-28.80; adjusted P = .003) and 3.87 (95% CI, 1.10-13.60; adjusted P = .035), respectively. Individuals in the third-tertile PRS had significantly lower CRP concentrations (4.61 ± 1.3 mg/L vs 9.60 ± 2.6 mg/L, P = .019) when consuming ≥14% energy from protein (with an average of 18.0% ± 2.4%, 43.0% ± 7.7%, and 39.0% ± 8.0% energy from protein, carbohydrate, and fat per day). In conclusion, third-tertile PRS was significantly associated with increased odds of elevated CRP; higher protein intake may alleviate inflammatory status and reduce CRP concentrations systemically in those individuals.

Combination of Talazoparib and Calcitriol Enhanced Anticancer Effect in Triple-Negative Breast Cancer Cell Lines.

Monotherapy for triple-negative breast cancer (TNBC) is often ineffective. This study aimed to investigate the effect of calcitriol and talazoparib combination on cell proliferation, migration, apoptosis and cell cycle in TNBC cell lines. Monotherapies and their combination were studied for (i.) antiproliferative effect (using real-time cell analyzer assay), (ii.) cell migration (CIM-Plate assay), and (iii.) apoptosis and cell cycle analysis (flow cytometry) in MDA-MB-468 and BT-20 cell lines. The optimal antiproliferative concentration of talazoparib and calcitriol in BT-20 was 91.6 and 10 µM, respectively, and in MDA-MB-468, it was 1 mM and 10 µM. Combined treatment significantly increased inhibition of cell migration in both cell lines. The combined treatment in BT-20 significantly increased late apoptosis (89.05 vs. control 0.63%) and S and G2/M populations (31.95 and 24.29% vs. control (18.62 and 12.09%)). Combined treatment in MDA-MB-468 significantly increased the S population (45.72%) and decreased G0/G1 (45.86%) vs. the control (26.79 and 59.78%, respectively). In MDA-MB-468, combined treatment significantly increased necrosis, early and late apoptosis (7.13, 33.53 and 47.1% vs. control (1.5, 3.1 and 2.83%, respectively)). Talazoparib and calcitriol combination significantly affected cell proliferation and migration, induction of apoptosis and necrosis in TNBC cell lines. This combination could be useful as a formulation to treat TNBC.

Effect of Rice (Oryza sativa L.) Ceramides Supplementation on Improving Skin Barrier Functions and Depigmentation: An Open-Label Prospective Study.

Ceramides plays a crucial role in maintaining skin barrier function. Although foregoing evidence supported beneficial effects of topical ceramides for restoration of the skin barrier, studies on oral ceramides are extremely scarce, with most published data collected from in vivo and in vitro models. Thus, this study aimed to evaluate the efficacy of rice ceramides (RC) supplementation to improve skin barrier function and as a depigmenting agent through comprehensive clinical assessments. This study investigated the beneficial effects of orally administered RC supplementation in 50 voluntary participants. Skin hydration, firmness and elasticity, transepidermal water loss (TEWL), melanin index (MI), erythema index (EI), sebum production, pH, and wrinkle severity were assessed at baseline and during monthly follow-up visits. RC supplementation was found to significantly (p < 0.01) improve skin hydration, sebum production, firmness and elasticity, and wrinkle severity for three assessed areas, namely the left cheek, dorsal neck, and right inner forearm. Additionally, RC significantly (p < 0.01) reduced the rates of TEWL, levels of MI and EI. Analyses of data indicated that participants at older age were more responsive towards the effect of RC supplementation. Our findings suggest that RC supplementation can effectively improve skin barrier function, reduce wrinkle severity, and reduce pigmentation.

Effects of Ambient Particulate Matter (PM2.5) Exposure on Calorie Intake and Appetite of Outdoor Workers.

Malaysia has been experiencing smoke-haze episodes almost annually for the past few decades. PM2.5 is the main component in haze and causes harmful impacts on health due to its small aerodynamic size. This study aimed to explore the implications of PM2.5 exposure on the dietary intake of working individuals. Two phased 13-weeks follow-up study was conducted involving 440 participants, consisting of two cohorts of outdoor and indoor workers. Ambient PM2.5 concentrations were monitored using DustTrakTM DRX Aerosol Monitor. Data on Simplified Nutritional Appetite Questionnaire (SNAQ) and 24 h diet recall were collected weekly. The highest PM2.5 concentration of 122.90 ± 2.07 µg/m3 was recorded in August, and it vastly exceeded the standard value stipulated by US EPA and WHO. SNAQ scores and calorie intake were found to be significantly (p < 0.05) associated with changes in PM2.5 exposure of outdoor workers. Several moderate and positive correlations (R-value ranged from 0.4 to 0.6) were established between SNAQ scores, calorie intake and PM2.5 exposure. Overall findings suggested that long hours of PM2.5 exposure affect personal dietary intake, potentially increasing the risk of metabolic syndromes and other undesired health conditions. The current policy should be strengthened to safeguard the well-being of outdoor workers.

Recombinant C-Reactive Protein: A Potential Candidate for the Treatment of Cutaneous Leishmaniasis of BALB/c Mice Caused by Leishmania major.

PURPOSE: Leishmaniasis, a widespread parasitic disease, is a public health concern that is endemic in more than 90 countries. Owing to the drug resistance and also undesirable complications, designing new therapeutic methods are essential. C-reactive protein (CRP) is an acute phase protein of plasma with several immune modulatory functions. This study aimed to evaluate the effect of human recombinant CRP (hrCRP) on treating cutaneous leishmaniasis in mice models. METHODS: hrCRP was expressed in E. coli Rosetta-gami and extracted from the SDS-PAGE gel. Male BALB/c mice were inoculated subcutaneously at the base of their tails by 1 × 105 stationary-phase of Leishmania major promastigotes (MHRO/IR/75/ER) suspended in sterile phosphate buffered saline (PBS). Nodules and subsequently, ulcers developed 14 days post-injection. 1.5 µg of the purified protein was administered on lesions of pre-infected mice by Leishmania major in the intervention group for five consecutive days. RESULTS: The mean area of the lesions was decreased by about seven folds in the intervention group as compared to the control group after two weeks of the treatment (p = 0.024). The results were verified by the real-time polymerase chain reaction so that the parasite burden was determined 27 times in the control group as compared to the intervention group (p = 0.02). Two weeks after treatment, the conversion of the lesions to scars in the intervention group was observed. CONCLUSION: The results indicate a potential therapeutic role for hrCRP in improving cutaneous leishmaniasis due to Leishmania major in mice models. The healing was in a stage-dependent manner.

Association of ADRB2 rs1042713 with Obesity and Obesity-Related Phenotypes and Its Interaction with Dietary Fat in Modulating Glycaemic Indices in Malaysian Adults.

Gene-diet interaction studies have reported that individual variations in phenotypic traits may be due to variations in individual diet. Our study aimed to evaluate (i) the association of ADRB2 rs1042713 with obesity and obesity-related metabolic parameters and (ii) the effect of dietary nutrients on these associations in Malaysian adults. ADRB2 genotyping, dietary, physical activity, anthropometric, and biochemical data were collected from 79 obese and 99 nonobese individuals. Logistic regression revealed no association between ADRB2 rs1042713 and obesity (p=0.725). However, the carriers of G allele (AG + GG genotypes) of rs1042713 were associated with increased odds of insulin resistance, 2.83 (CI = 1.04-7.70, adjusted p=0.042), in the dominant model, even after adjusting for potential confounders. Obese individuals carrying the G allele were associated with higher total cholesterol (p=0.011), LDL cholesterol levels (p=0.008), and total cholesterol/HDL cholesterol ratio (p=0.048), compared to the noncarriers (AA), even after adjusting for potential confounders. Irrespective of obesity, the carriers of GG genotype had significantly lower fasting glucose levels with low saturated fatty acid intake (<7.3% of TE/day) (4.92 ± 0.1 mmol/L vs 5.80 ± 0.3 mmol/L, p=0.011) and high intake of polyunsaturated fatty acid:saturated fatty acid ratio (≥0.8/day) (4.83 ± 0.1 mmol/L vs 5.93 ± 0.4 mmol/L, p=0.006). Moreover, the carriers of GG genotype with high polyunsaturated fatty acid intake (≥6% of TE/day) had significantly lower HOMA-IR (1.5 ± 0.3 vs 3.0 ± 0.7, p=0.026) and fasting insulin levels (6.8 ± 1.6 µU/mL vs 11.4 ± 2.1 µU/mL, p=0.036). These effects were not found in the noncarriers (AA). In conclusion, G allele carriers of ADRB2 rs1042713 were associated with increased odds of insulin resistance. Obese individuals carrying G allele were compromised with higher blood lipid levels. Although it is premature to report gene-diet interaction on the regulation of glucose and insulin levels in Malaysians, we suggest that higher quantity of PUFA-rich food sources in regular diet may benefit overweight and obese Malaysian adults metabolically. Large-scale studies are required to replicate and confirm the current findings in the Malaysian population.

Lifestyle Interventions for Weight Control Modified by Genetic Variation: A Review of the Evidence.

BACKGROUND/AIMS: Excess weight gain is a result of the interaction between diet, environment, and genes. Evidence suggests that responses to lifestyle interventions to manage weight are partially modified by genetic factors. This review is aimed at summarizing the current evidence from studies done on gene variants - single nucleotide polymorphisms (SNPs) - and intervention outcomes on weight loss and obesity-related traits. METHODS: Intervention studies published in English between 2000 and August 2018 were retrieved from PubMed, Google Scholar, and Web of Science using various keywords. RESULTS: This article is a review of 36 studies conducted in 13 different countries which included a total of 15,931 participants between 19 and 70 years of age. The effect of 26 genes and 64 SNPs on the reduction of body weight and metabolic risk factors in response to diet, exercise, and lifestyle interventions was reviewed. CONCLUSION: Gene-lifestyle interaction studies on the same candidate gene in different populations have reported information which is challenging to interpret. Thus, it is difficult to arrive at a particular model for a strategy on weight management at this point in time. Most of the intervention studies focus on the effect of variants of a single candidate gene on weight loss. Further evidence from large-scale studies is necessary to assess the effect of multiple candidate genes to compute a gene score that could be used in a model intervention programme. Our review suggests that a healthy lifestyle with a balanced diet and regular physical activity will benefit individuals who carry the risk alleles of the obesity-related candidate genes. This message should be the mainstay of the recommendations and guidelines published by nutrition societies across the world.

Feasibility and toxicity of hematopoietic stem cell transplant in multiple sclerosis.

Multiple sclerosis is a debilitating disease of the central nervous system. It affects people of all ages but is more prevalent among 20-40 year olds. Patients with MS can be presented with potentially any neurological symptom depending on the location of the lesion. A quarter of patients with MS suffer from bilateral lower limb spasticity among other symptoms. These devastating effects can be detrimental to the patient's quality of life. Hematopoietic stem cells (HSCs) have been used as a treatment for MS over the past 2 decades but their safety and efficacy has are undetermined. The objective of this study is to evaluate the feasibility and toxicity of autologous HSCs transplantation in MS. A literature search was done from 1997 to 2016 using different keywords. A total of 9 articles, which met the inclusion and exclusion criteria, were included in this review. The type of conditioning regimen and technique of stem cell mobilization are summarized and compared in this study. All studies reported high-dose immunosuppressive therapy with autologous HSCs transplantation being an effective treatment option for severe cases of multiple sclerosis. Fever, sepsis, and immunosuppression side effects were the most observed adverse effects that were reported in the selected studies. HSCs is a feasible treatment for patients with MS; nevertheless the safety is still a concern due to chemo toxicity.

The therapeutic potential of stem cells and progenitor cells for the treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is usually seen in those above 50 years old. Current medical treatments only provide symptomatic relief but cannot cure the disease. There are claims that PD can be cured by stem cell transplant. The present study is aimed to assess the clinical potency and safety of stem cell in treating PD. A total of eleven articles were included for analysis, with four randomised control trials (RCTs), five non-RCTs and 2 follow up studies. All the four non-RCTs showed improvement of Unified Parkinson's Disease Rating Scale with no adverse events. However, results from RCTs showed no significant differences in the rating score among the transplant group and the Sham surgery group. The secondary analysis of one study showed a significant improvement of the rating score in those patients aged 60 and younger. Transplant group also associated with an overall higher incidence of adverse events. In conclusion, the RCTs and non-RCTs produced opposite results. When the studies were performed as non-RCTs in small number of patients, they showed promising result in the patients. It could say that currently the use of stem cell/progenitor cells in treating PD need much research despite having the implanted stem cell to be able to survive and integrated. The survival of implanted dopamine neurons in the striatum, however, does not indicate a success in correcting PD symptoms. Further investigations will shed light on the application and mechanism of action of stem cells in treating PD. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s13770-016-9093-2 and is accessible for authorized users.