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Pharmacophore Based Virtual Screening Approach to Identify Selective PDE4B Inhibitors

Gaurav A, Gautam V

Iran J Pharm Res, 2017;16(3):910-923.
PMID: 29201082

Phosphodiesterase 4 (PDE4) has been established as a promising target in asthma and chronic obstructive pulmonary disease. PDE4B subtype selective inhibitors are known to reduce the dose limiting adverse effect associated with non-selective PDE4B inhibitors. This makes the development of PDE4B subtype selective inhibitors a desirable research goal. To achieve this goal, ligand based pharmacophore modeling approach is employed. Separate pharmacophore hypotheses for PDE4B and PDE4D inhibitors were generated using HypoGen algorithm and 106 PDE4 inhibitors from literature having thiopyrano [3,2-d] Pyrimidines, 2-arylpyrimidines, and triazines skeleton. Suitable training and test sets were created using the molecules as per the guidelines available for HypoGen program. Training set was used for hypothesis development while test set was used for validation purpose. Fisher validation was also used to test the significance of the developed hypothesis. The validated pharmacophore hypotheses for PDE4B and PDE4D inhibitors were used in sequential virtual screening of zinc database of drug like molecules to identify selective PDE4B inhibitors. The hits were screened for their estimated activity and fit value. The top hit was subjected to docking into the active sites of PDE4B and PDE4D to confirm its selectivity for PDE4B. The hits are proposed to be evaluated further using in-vitro assays.

Matched MeSH terms: Pulmonary Disease, Chronic Obstructive
Chronic Cold-Water-Induced Hypothermia Impairs Memory Retrieval and Nepeta menthoides as a Traditional "Hot" Herb Reverses the Impairment

Ahmadian-Attar MM, Ahmadiani A, Kamalinejad M, Dargahi L, Mosaddegh M

Iran J Pharm Res, 2014;13(Suppl):185-93.
PMID: 24711845

Iranian Traditional Medicine (ITM) describes a kind of dementia with similar signs and symptoms of Alzheimer's disease (AD). It explains the pathology of dementia with cold intemperament of the brain, which means that the brain is colder than its healthy form. ITM strategy for treatment of dementia is to heat the brain up by medical "hot" herbs. Nepeta menthoides (NM) is one of these "hot" herbs. To evaluate the veracity of ITM concept about dementia and its treatment, we first try to examine if coldness of brain can make memory impairment. If so, can NM reverse memory impairment? Rats in cold-water-induced hypothermic (CWH) groups were immersed up to the neck in 3.5 °C water, for 5 min during 14 consecutive days. As a control, rats were forced to swim in warm water at the same conditions. To eliminate the impact of forced swimming stress, a group of intact rats was also added. After last swimming in day 14, some groups received drug (100 or 500 mg/ Kg aqueous extract of NM) or vehicle via i.p. injection. Learning and memory were assessed by Morris water maze, and tau hyperphosphorylation was measured by western blotting. The results showed that CWH impairs learning and memory and induces tau hyperphosphorylation. 100 mg/Kg of NM reversed memory impairment as well as tau hyperphosphorylation. ITM theory about the relationship between brain hypothermia and dementia is in accordance with our findings.

Matched MeSH terms: Alzheimer Disease
Bursal transcriptome profiling of different inbred chicken lines reveals key differentially expressed genes at 3 days post-infection with very virulent infectious bursal disease virus

Farhanah MI, Yasmin AR, Mat Isa N, Hair-Bejo M, Ideris A, Powers C, et al.

J Gen Virol, 2018 Jan;99(1):21-35.
PMID: 29058656 DOI: 10.1099/jgv.0.000956

Infectious bursal disease is a highly contagious disease in the poultry industry and causes immunosuppression in chickens. Genome-wide regulations of immune response genes of inbred chickens with different genetic backgrounds, following very virulent infectious bursal disease virus (vvIBDV) infection are poorly characterized. Therefore, this study aims to analyse the bursal tissue transcriptome of six inbred chicken lines 6, 7, 15, N, O and P following infection with vvIBDV strain UK661 using strand-specific next-generation sequencing, by highlighting important genes and pathways involved in the infected chicken during peak infection at 3 days post-infection. All infected chickens succumbed to the infection without major variations among the different lines. However, based on the viral loads and bursal lesion scoring, lines P and 6 can be considered as the most susceptible lines, while lines 15 and N were regarded as the least affected lines. Transcriptome profiling of the bursa identified 4588 genes to be differentially expressed, with 2985 upregulated and 1642 downregulated genes, in which these genes were commonly or uniquely detected in all or several infected lines. Genes that were upregulated are primarily pro-inflammatory cytokines, chemokines and IFN-related. Various genes that are associated with B-cell functions and genes related to apoptosis were downregulated, together with the genes involved in p53 signalling. In conclusion, bursal transcriptome profiles of different inbred lines showed differential expressions of pro-inflammatory cytokines and chemokines, Th1 cytokines, JAK-STAT signalling genes, MAPK signalling genes, and their related pathways following vvIBDV infection.

Matched MeSH terms: Disease Susceptibility; Infectious bursal disease virus/growth & development; Infectious bursal disease virus/pathogenicity*
Fulltext Effects of Photodynamic Therapy on Tumor Metabolism and Oxygenation Revealed by Fluorescence and Phosphorescence Lifetime Imaging

Shirmanova MV, Lukina MM, Sirotkina MA, Shimolina LE, Dudenkova VV, Ignatova NI, et al.

Int J Mol Sci, 2024 Jan 30;25(3).
PMID: 38338976 DOI: 10.3390/ijms25031703

This work was aimed at the complex analysis of the metabolic and oxygen statuses of tumors in vivo after photodynamic therapy (PDT). Studies were conducted on mouse tumor model using two types of photosensitizers-chlorin e6-based drug Photoditazine predominantly targeted to the vasculature and genetically encoded photosensitizer KillerRed targeted to the chromatin. Metabolism of tumor cells was assessed by the fluorescence lifetime of the metabolic redox-cofactor NAD(P)H, using fluorescence lifetime imaging. Oxygen content was assessed using phosphorescence lifetime macro-imaging with an oxygen-sensitive probe. For visualization of the perfused microvasculature, an optical coherence tomography-based angiography was used. It was found that PDT induces different alterations in cellular metabolism, depending on the degree of oxygen depletion. Moderate decrease in oxygen in the case of KillerRed was accompanied by an increase in the fraction of free NAD(P)H, an indicator of glycolytic switch, early after the treatment. Severe hypoxia after PDT with Photoditazine resulted from a vascular shutdown yielded in a persistent increase in protein-bound (mitochondrial) fraction of NAD(P)H. These findings improve our understanding of physiological mechanisms of PDT in cellular and vascular modes and can be useful to develop new approaches to monitoring its efficacy.

Matched MeSH terms: Disease Models, Animal
Global, regional, and national burdens of depressive disorders in adolescents and young adults aged 10-24 years from 1990 to 2019: A trend analysis based on the Global Burden of Disease Study 2019

Luo J, Tang L, Kong X, Li Y

Asian J Psychiatr, 2024 Feb;92:103905.
PMID: 38262303 DOI: 10.1016/j.ajp.2023.103905

BACKGROUND: Depressive disorders (DD) including dysthymia and major depressive disorder (MDD) are common among adolescents and young adults. However, global trends in DD burden remain unclear.
METHODS: We analysed data from the Global Burden of Disease 2019 study on incidence, prevalence, disability-adjusted life years (DALYs), and mortality due to DD from 1990 to 2019 at global, regional and national levels.
RESULTS: Globally, dysthymia incidence increased notably in females, older age groups, and lower-middle income countries from 1990 to 2019. In contrast, MDD incidence decreased slightly over this period except in high-income North America. Females and middle-income countries had the highest dysthymia burden while North America had the highest MDD incidence and DALYs. Oman and Malaysia experienced largest increases in dysthymia and MDD burden respectively.
CONCLUSION: Despite certain global indicators suggesting a leveling off or decrease, it's clear that depressive disorders continue to be a significant and increasing issue, particularly among women, teenagers, and young adults. Differences between regions and countries indicate that specific interventions aimed at addressing economic inequalities, improving healthcare systems, and taking cultural factors into account could make a real difference in lessening the burden of depressive disorders. More research is needed to understand what's driving these trends so that we can develop better strategies for preventing and managing these conditions.

Matched MeSH terms: Global Burden of Disease
Increased RUNX1 mutations in breast cancer disease progression

Ariffin NS

Pathol Res Pract, 2024 Feb;254:155076.
PMID: 38219493 DOI: 10.1016/j.prp.2023.155076

Despite advances in screening, therapy and surveillance, breast cancer remains threatening to women. Worst, patients suffer from side effects of treatments and cancer cells become resistant. The emergence of RUNX1 in breast cancer has put it in a spotlight due to its roles in the disease progression. It also plays important roles in normal mammary glands such as for cell growth, proliferation, migration and stemness. However, mutations in the RUNX1 gene have changed the regulation of these phenotypes and the full spectrum of its implications in breast cancer patients is unknown. In this study therefore, the pattern of RUNX1 mutations in breast cancer patients was examined to understand its fundamental impacts on the disease. The perturbation of RUNX1 and its mutations in breast cancer was elucidated through different studies reported in cBioPortal in the past ten years. From our analyses, the majority of RUNX1 mutations were found in the primary breast cancer, with women constituted most of the mutations, especially on the left side of the breast. Similarly, increased number of mutations was observed in ER-positive breast cancer patients and this was also the case at the early stage of the disease development. The level of RUNX1 mutations also increased gradually as patients got older and the peak was highest in the patients of 60-70 years old. Altogether, these data indicated that the mutated RUNX1 gene contributed to the progression of breast cancer and understanding of its regulatory mechanisms is crucial to therapeutically target this gene in the future.

Matched MeSH terms: Disease Progression
Fulltext The paediatric global musculoskeletal task force - 'towards better MSK health for all'

Foster HE, Scott C, Tiderius CJ, Dobbs MB

Pediatr Rheumatol Online J, 2020 Jul 14;18(1):60.
PMID: 32664961 DOI: 10.1186/s12969-020-00451-8

There is increasing concern about the emerging global non-communicable diseases (NCDs) burden. The focus has mainly been on NCDs in adults but it is important that MSK morbidity in both children and adults is included in strategic planning. There have been considerable advances in the understanding and treatment options for children and young people (CYP) and clinical outcomes are improving for those who can access such high quality care. However vast inequity exists and there are many CYP who live in areas of the world with high burden of health care challenges, compounded by paucity of specialist care and limited access to treatments. The Paediatric Global Musculoskeletal Task Force aims to raise awareness about unmet needs for CYP with MSK conditions, promotion of MSK health through lifestyle and the avoidance of injury. We aim to leverage change through 'working together better'.

Matched MeSH terms: Global Burden of Disease
Fulltext Predictors of stakeholders' intention to adopt nutrigenomics

Mustapa MAC, Amin L, Frewer LJ

Genes Nutr, 2020 Sep 22;15(1):16.
PMID: 32962632 DOI: 10.1186/s12263-020-00676-y

BACKGROUND: Nutrigenomics is an emerging science that studies the relationship between genes, diet and nutrients that can help prevent chronic disease. The development of this science depends on whether the public accept its application; therefore, predicting their intention to adopt it is important for its successful implementation.
OBJECTIVE: This study aims to analyse Malaysian stakeholders' intentions to adopt nutrigenomics, and determines the factors that influence their intentions.
METHODS: A survey was conducted based on the responses of 421 adults (aged 18 years and older) and comprising two stakeholder groups: healthcare providers (n = 221) and patients (n = 200) who were located in the Klang Valley, Malaysia. The SPSS software was used to analyse the descriptive statistics of intention to adopt nutrigenomics and the SmartPLS software was used to determine the predicting factors affecting their decisions to adopt nutrigenomics.
RESULTS: The results show that the stakeholders perceived the benefits of nutrigenomics as outweighing its risks, suggesting that the perceived benefits represent the most important direct predictor of the intention to adopt nutrigenomics. The perceived risks of nutrigenomics, trust in key players, engagement with medical genetics and religiosity also predict the intention to adopt nutrigenomics. Additionally, the perceived benefits of nutrigenomics served as a mediator for four factors: perceived risks of nutrigenomics, engagement with medical genetics, trust in key players and religiosity, whilst the perceived risks were a mediator for engagement with medical genetics.
CONCLUSION: The findings of this study suggest that the intentions of Malaysian stakeholders to adopt nutrigenomics are a complex decision-making process where all the previously mentioned factors interact. Although the results showed that the stakeholders in Malaysia were highly positive towards nutrigenomics, they were also cautious about adopting it.

Matched MeSH terms: Chronic Disease
Psychosocial assessment of quarantine (sign-on and sign-off) among oil and gas workers in Malaysia during COVID-19 outbreak

Shohaime NA, Masngut MI, Aris MSM

Med J Malaysia, 2024 Mar;79(Suppl 1):96-103.
PMID: 38555892

INTRODUCTION: COVID-19 still wreaking havoc in Malaysia, with 3,221,680 cases and 32,326 deaths as of 20 February 2022. In the Oil and Gas industry, implementing quarantine before mobilising to or after mobilising from onshore and offshore locations was mandatory to help stop the spread of the virus. However, previous studies have shown that quarantine can significantly impact public mental health. This study intends to assess the psychosocial stress experienced by Oil and Gas industry employees during periods of quarantine in various regions (PMA: Terengganu, SBA: Sabah, SKA: Sarawak) and between onshore and offshore employees. Additionally, it aims to identify the factors that are linked to psychosocial stress in this workforce.
MATERIALS AND METHODS: A cross-sectional study involving 86 respondents was conducted using an online survey between the middle of March and April 2022. The Perceived Stress Scale (PSS) developed by Cohen et al., (1983) was used to assess the stress levels of individuals. Data analysis was carried out using the SPSS statistical program, which included descriptive statistics, Mann-Whitney, Kruskal Wallis and Linear Regression tests.
RESULTS: The majority of respondents, 75.6% (n=65) reported moderate stress levels, while 14.0% (n=12) declared severe stress levels. The Mann-Whitney test showed no significant difference in psychosocial stress scores among workers between onshore and offshore (χ2=-0.523, p=0.601), whereas the Kruskal Wallis test showed a significant difference in psychosocial stress scores among workers between states (PMA, SKA, and SBA) (χ2=6.415, p=0.040). According to the regression test, workers with medical histories of diabetes and Covid-19 (R2=0.158) (p<0.005) are two factors linked to psychosocial stress.
CONCLUSION: The study found that there were significant differences in psychosocial stress among oil and gas workers between SKA, SBA, and PMA due to quarantine activity. Mobile workers and those with certain medical histories were identified as being particularly vulnerable to psychosocial stress. However, it was noted that the overall improvement in the quarantine period had a positive impact on the mental health of these workers.

Matched MeSH terms: Disease Outbreaks
Fulltext Lives versus Livelihoods? Perceived economic risk has a stronger association with support for COVID-19 preventive measures than perceived health risk

Nisa CF, Bélanger JJ, Faller DG, Buttrick NR, Mierau JO, Austin MMK, et al.

Sci Rep, 2021 May 06;11(1):9669.
PMID: 33958617 DOI: 10.1038/s41598-021-88314-4

This paper examines whether compliance with COVID-19 mitigation measures is motivated by wanting to save lives or save the economy (or both), and which implications this carries to fight the pandemic. National representative samples were collected from 24 countries (N = 25,435). The main predictors were (1) perceived risk to contract coronavirus, (2) perceived risk to suffer economic losses due to coronavirus, and (3) their interaction effect. Individual and country-level variables were added as covariates in multilevel regression models. We examined compliance with various preventive health behaviors and support for strict containment policies. Results show that perceived economic risk consistently predicted mitigation behavior and policy support-and its effects were positive. Perceived health risk had mixed effects. Only two significant interactions between health and economic risk were identified-both positive.

Matched MeSH terms: Communicable Disease Control
Fulltext Trust predicts COVID-19 prescribed and discretionary behavioral intentions in 23 countries

Pagliaro S, Sacchi S, Pacilli MG, Brambilla M, Lionetti F, Bettache K, et al.

PLoS One, 2021;16(3):e0248334.
PMID: 33690672 DOI: 10.1371/journal.pone.0248334

The worldwide spread of a new coronavirus (SARS-CoV-2) since December 2019 has posed a severe threat to individuals' well-being. While the world at large is waiting that the released vaccines immunize most citizens, public health experts suggest that, in the meantime, it is only through behavior change that the spread of COVID-19 can be controlled. Importantly, the required behaviors are aimed not only at safeguarding one's own health. Instead, individuals are asked to adapt their behaviors to protect the community at large. This raises the question of which social concerns and moral principles make people willing to do so. We considered in 23 countries (N = 6948) individuals' willingness to engage in prescribed and discretionary behaviors, as well as country-level and individual-level factors that might drive such behavioral intentions. Results from multilevel multiple regressions, with country as the nesting variable, showed that publicized number of infections were not significantly related to individual intentions to comply with the prescribed measures and intentions to engage in discretionary prosocial behaviors. Instead, psychological differences in terms of trust in government, citizens, and in particular toward science predicted individuals' behavioral intentions across countries. The more people endorsed moral principles of fairness and care (vs. loyalty and authority), the more they were inclined to report trust in science, which, in turn, statistically predicted prescribed and discretionary behavioral intentions. Results have implications for the type of intervention and public communication strategies that should be most effective to induce the behavioral changes that are needed to control the COVID-19 outbreak.

Matched MeSH terms: Disease Outbreaks
Fulltext Eradication of Helicobacter pylori infection improves levodopa action, clinical symptoms and quality of life in patients with Parkinson's disease

Hashim H, Azmin S, Razlan H, Yahya NW, Tan HJ, Manaf MR, et al.

PLoS One, 2014;9(11):e112330.
PMID: 25411976 DOI: 10.1371/journal.pone.0112330

BACKGROUND: Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson's disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients.
METHODS: A prospective study involving idiopathic PD patients on levodopa therapy. 13C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa 'onset' time and ON-duration were recorded.
RESULTS: Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement.
CONCLUSIONS: H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02112812.

Matched MeSH terms: Parkinson Disease/drug therapy*; Parkinson Disease/microbiology*; Parkinson Disease/pathology
Fulltext Medicinal Plants and Their Inhibitory Activities against Pancreatic Lipase: A Review

Seyedan A, Alshawsh MA, Alshagga MA, Koosha S, Mohamed Z

Evid Based Complement Alternat Med, 2015;2015:973143.
PMID: 26640503 DOI: 10.1155/2015/973143

Obesity is recognized as a major life style disorder especially in developing countries and it is prevailing at an alarming speed in new world countries due to fast food intake, industrialization, and reduction of physical activity. Furthermore, it is associated with a vast number of chronic diseases and disabilities. To date, relatively effective drugs, from either natural or synthetic sources, are generally associated with serious side effects, often leading to cessation of clinical trials or even withdrawal from the market. In order to find new compounds which are more effective or with less adverse effects compared to orlistat, the drug that has been approved for obesity, new compounds isolated from natural products are being identified and screened for antiobesity effects, in particular, for their pancreatic lipase inhibitory effect. Pancreatic lipase inhibitory activity has been extensively used for the determination of potential efficacy of natural products as antiobesity agents. In attempts to identify natural products for overcoming obesity, more researches have been focused on the identification of newer pancreatic lipase inhibitors with less unpleasant adverse effects. In this review, we consider the potential role of plants that have been investigated for their pancreatic lipase inhibitory activity.

Matched MeSH terms: Chronic Disease
Fulltext Eight Weeks of Cosmos caudatus (Ulam Raja) Supplementation Improves Glycemic Status in Patients with Type 2 Diabetes: A Randomized Controlled Trial

Cheng SH, Ismail A, Anthony J, Ng OC, Hamid AA, Barakatun-Nisak MY

Evid Based Complement Alternat Med, 2015;2015:405615.
PMID: 26713097 DOI: 10.1155/2015/405615

Objectives. Optimizing glycemic control is crucial to prevent type 2 diabetes related complications. Cosmos caudatus is reported to have promising effect in improving plasma blood glucose in an animal model. However, its impact on human remains ambiguous. This study was carried out to evaluate the effectiveness of C. caudatus on glycemic status in patients with type 2 diabetes. Materials and Methods. In this randomized controlled trial with two-arm parallel-group design, a total of 101 subjects with type 2 diabetes were randomly allocated to diabetic-ulam or diabetic controls for eight weeks. Subjects in diabetic-ulam group consumed 15 g of C. caudatus daily for eight weeks while diabetic controls abstained from taking C. caudatus. Both groups received the standard lifestyle advice. Results. After 8 weeks of supplementation, C. caudatus significantly reduced serum insulin (-1.16 versus +3.91), reduced HOMA-IR (-1.09 versus +1.34), and increased QUICKI (+0.05 versus -0.03) in diabetic-ulam group compared with the diabetic controls. HbA1C level was improved although it is not statistically significant (-0.76% versus -0.37%). C. caudatus was safe to consume. Conclusions. C. caudatus supplementation significantly improves insulin resistance and insulin sensitivity in patients with type 2 diabetes.

Matched MeSH terms: Disease Models, Animal
Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Mueller SH, Lai AG, Valkovskaya M, Michailidou K, Bolla MK, Wang Q, et al.

Genome Med, 2023 Jan 26;15(1):7.
PMID: 36703164 DOI: 10.1186/s13073-022-01152-5

BACKGROUND: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.
METHODS: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.
RESULTS: In European ancestry samples, 14 genes were significantly associated (q

Matched MeSH terms: Genetic Predisposition to Disease
Fulltext Prevalence of diabetic retinopathy, proliferative diabetic retinopathy and non-proliferative diabetic retinopathy in Asian T2DM patients: a systematic review and Meta-analysis

Yang QH, Zhang Y, Zhang XM, Li XR

Int J Ophthalmol, 2019;12(2):302-311.
PMID: 30809489 DOI: 10.18240/ijo.2019.02.19

AIM: To investigate the pooled prevalence of diabetic retinopathy (DR), proliferative DR (PDR) and nonproliferative DR (NPDR) in Asian type 2 diabetes mellitus (T2DM) patients.
METHODS: We performed a systematic search online search using PubMed, EMBASE, Web of Science, the Cochrane Library, and China WeiPu Library to identify eligible studies that reported the prevalence of DR, PDR and NPDR in Asian T2DM patients. Effect size (ES) with 95% confidence interval (CI) was used to evaluate the prevalence of DR, PDR and NPDR in Asian T2DM patients, respectively.
RESULTS: There were 41 references and 48 995 T2DM patients involved in this study. The prevalence of DR, PDR, and NPDR was 28%, 6%, and 27% in T2DM patients, respectively; while the prevalence of PDR and NPDR in DR patients was 17% and 83%, respectively. Subgroup analysis showed that prevalence of DR in T2DM patients from Singaporean, Indian, South Korean, Malaysian, Asian, and Chinese was 33%, 42%, 16%, 35%, 21% and 25%, respectively. In T2DM patients with NPDR from Indian, South Korean, Malaysian, Asian, Chinese, higher prevalence was found than that in PDR patients (45% vs 17%, 13% vs 3%, 30% vs 5%, 23% vs 2% and 22% vs 3%), as well as in DR patients (74% vs 26%, 81% vs 19%, 86% vs 14%, 92% vs 8% and 85% vs 15%). The prevalence of PDR in T2DM from India was higher than patients from other locations of Asia, and the same results were also observed in NPDR patients.
CONCLUSION: In either T2DM Asian patients or DR patients, NPDR is more common than PDR. Based on our results, we should pay more attention to NPDR screening and management in T2DM patients, and we also recommend suitable interventions to prevent its progression.

Matched MeSH terms: Disease Progression
Fulltext A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

Zhong J, Jermusyk A, Wu L, Hoskins JW, Collins I, Mocci E, et al.

J Natl Cancer Inst, 2020 Oct 01;112(10):1003-1012.
PMID: 31917448 DOI: 10.1093/jnci/djz246

BACKGROUND: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown.
METHODS: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples).
RESULTS: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction.
CONCLUSIONS: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.

Matched MeSH terms: Genetic Predisposition to Disease
Fulltext In vitro and in vivo toxicity of garcinia or hydroxycitric Acid: a review

Chuah LO, Yeap SK, Ho WY, Beh BK, Alitheen NB

Evid Based Complement Alternat Med, 2012;2012:197920.
PMID: 22924054 DOI: 10.1155/2012/197920

Obesity is one of the pandemic chronic diseases commonly associated with health disorders such as heart attack, high blood pressure, diabetes or even cancer. Among the current natural products for obesity and weight control, Garcinia or more specifically hydroxycitric acid (HCA) extracted from Garcinia has been widely used. The evaluation of the potential toxicity of weight control supplement is of the utmost importance as it requires long term continuous consumption in order to maintain its effects. Majority of reports demonstrated the efficacy of Garcinia/HCA without any toxicity found. However, a few clinical toxicity reports on weight-loss diet supplements of which some were combinations that included Garcinia/HCA as an active ingredient showed potential toxicity towards spermatogenesis. Nonetheless, it cannot be concluded that Garcinia/HCA is unsafe. Those products which have been reported to possess adverse effects are either polyherbal or multi-component in nature. To date, there is no case study or report showing the direct adverse effect of HCA. The structure, mechanism of action, long history of the use of Garcinia/HCA and comprehensive scientific evidence had shown "no observed adverse effect level (NOAEL)" at levels up to 2800 mg/day, suggesting its safety for use.

Matched MeSH terms: Chronic Disease
Fulltext Nutraceutical Use among Patients with Chronic Disease Attending Outpatient Clinics in a Tertiary Hospital

Mahmood NA, Hassan MR, Ahmad S, Mohd Nawi H, Pang NTP, Syed Abdul Rahim SS, et al.

Evid Based Complement Alternat Med, 2020;2020:9814815.
PMID: 33224262 DOI: 10.1155/2020/9814815

Food-drug interphase products, referring to nutraceuticals in this study, are a category of health products containing a combination of food ingredients with active substances for oral consumption. Many of these products are marketed as an alternative to prescription medicine to treat various ailments despite the lack of scientific evidence, influencing patients with chronic diseases to consume nutraceutical products. This study aimed to determine the prevalence and factors associated with knowledge, attitude, and practice of nutraceutical use among patients with chronic disease attending to the outpatient clinic. This is a cross-sectional study involving patients with chronic disease at the outpatient specialist clinic. Samples were recruited from the outpatient clinic using convenience sampling. Data was collected using a self-administered questionnaire, which was self-constructed and validated. We found that the use of nutraceuticals was prevalent among 17.9% of respondents. More than half (60.9%) of the respondents have poor knowledge of nutraceutical and 53.1% of respondents have a positive attitude towards nutraceutical. Gender and morbidities were the factors associated with the practice of nutraceutical usage. Female patients are more likely to have increased use of nutraceutical than male patients and patients with multiple morbidities have higher odds of using nutraceutical than patients with single morbidities. There is a high number of patients who consume nutraceutical products and public knowledge of nutraceutical needs to be improved further. The government should develop appropriate regulation and monitoring of nutraceutical products.

Matched MeSH terms: Chronic Disease
Fulltext Response Surface Optimisation for the Production of Antioxidant Hydrolysates from Stone Fish Protein Using Bromelain

Auwal SM, Zarei M, Abdul-Hamid A, Saari N

Evid Based Complement Alternat Med, 2017;2017:4765463.
PMID: 29234403 DOI: 10.1155/2017/4765463

Protein hydrolysates produced from different food sources exhibit therapeutic potential and can be used in the management of chronic diseases. This study was targeted to optimise the conditions for the hydrolysis of stone fish protein to produce antioxidant hydrolysates using central composite design (CCD) by response surface methodology (RSM). The stone fish protein was hydrolysed under the optimum predicted conditions defined by pH (6.5), temperature (54°C), E/S ratio (1.5%), and hydrolysis time (360 min). The hydrolysates were then evaluated for 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) scavenging activity and ferrous ion- (Fe2+-) chelating activity. Results validation showed no significant difference between the experimental values of DPPH• scavenging activity (48.94%) and Fe2+-chelating activity (25.12%) obtained at 54.62% degree of hydrolysis (DH) compared to their corresponding predicted values of 49.79% and 24.08% at 53.08% DH, respectively. The hydrolysates demonstrated non-Newtonian behavior (n < 1) with stronger shear-thinning effect and higher viscosities at increasing concentration. Thus, RSM can be considered as a promising strategy to optimise the production of stone fish protein hydrolysates containing antioxidant peptides. It is hoped that this finding will enhance the potential of stone fish protein hydrolysates (SHs) as therapeutic bioactive ingredient in functional foods development.

Matched MeSH terms: Chronic Disease

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