SLC1A2 Gene Polymorphism Influences Methamphetamine-Induced Psychosis

SLC1A2 is a gene encoded for the excitatory amino acid transporter 2 which is responsible for glutamate reuptake from the synaptic cleft in the central nervous system. Recent studies have suggested that polymorphisms on glutamate transporters can affect drug dependence, leading to the development of neurological diseases and psychiatric disorders. Our study investigated the association of rs4755404 single nucleotide polymorphism (SNP) of the SLC1A2 gene with methamphetamine (METH) dependence and METH-induced psychosis and mania in a Malaysian population. The rs4755404 gene polymorphism was genotyped in METH-dependent male subjects (n = 285) and male control subjects (n = 251). The subjects consisted of the four ethnic groups in Malaysia (Malay, Chinese, Kadazan-Dusun, and Bajau). Interestingly, there was a significant association between rs4755404 polymorphism and METH-induced psychosis in the pooled METH-dependent subjects in terms of genotype frequency (p = 0.041). However, there was no significant association between rs4755404 polymorphism and METH dependence. Also, the rs455404 polymorphism was not significantly associated with METH-induced mania for both genotype frequencies and allele frequencies in the METH-dependent subjects, regardless of stratification into the different ethnicities. Our study suggests that the SLC1A2 rs4755404 gene polymorphism confers some susceptibility to METH-induced psychosis, especially for those who carry the GG homozygous genotype

SLC1A2 Gene Polymorphism Influences Methamphetamine-Induced Psychosis

SLC1A2 is a gene encoded for the excitatory amino acid transporter 2 which is responsible for glutamate reuptake from the synaptic cleft in the central nervous system. Recent studies have suggested that polymorphisms on glutamate transporters can affect drug dependence, leading to the development of neurological diseases and psychiatric disorders. Our study investigated the association of rs4755404 single nucleotide polymorphism (SNP) of the SLC1A2 gene with methamphetamine (METH) dependence and METH-induced psychosis and mania in a Malaysian population. The rs4755404 gene polymorphism was genotyped in METH-dependent male subjects (n = 285) and male control subjects (n = 251). The subjects consisted of the four ethnic groups in Malaysia (Malay, Chinese, Kadazan-Dusun, and Bajau). Interestingly, there was a significant association between rs4755404 polymorphism and METH-induced psychosis in the pooled METH-dependent subjects in terms of genotype frequency (p = 0.041). However, there was no significant association between rs4755404 polymorphism and METH dependence. Also, the rs455404 polymorphism was not significantly associated with METH-induced mania for both genotype frequencies and allele frequencies in the METH-dependent subjects, regardless of stratification into the different ethnicities. Our study suggests that the SLC1A2 rs4755404 gene polymorphism confers some susceptibility to METH-induced psychosis, especially for those who carry the GG homozygous genotype

Different domains of dengue research in Malaysia: A systematic review and meta-analysis of questionnaire-based studies

This review provided a systematic overview of the questionnaire-related dengue studies conducted in Malaysia and evaluated their reliability and validity used in the questionnaires. An extensive literature search was conducted using various electronic databases, including PubMed, EMBASE, Medline, and ScienceDirect. Systematic reviews and meta-analysis (PRISMA) were selected as the preferred item reporting method. Out of 88 identified dengue-related, 57 published from 2000 to April 2020 met the inclusion criteria and were included. Based on the meta-analysis, a poor mean score was obtained for knowledge (49%), attitude (44%), and preventive practice (55%). The study showed that the level of knowledge on cardinal signs and modes of transmission for dengue virus were highest among health care workers, followed by students (international and local) and lastly community residents. In treatment-seeking behaviours, only half of the respondents (50.8%) would send their child to the nearest health clinics or hospitals when a child became restless or lethargic. The acceptance rate for dengue vaccine, bacteria (Wolbachia), as a vector for dengue control and self-test diagnostic kit for dengue showed considerably high (88.4%, 70%, and 44.8%, respectively). Health belief model (HBM) constructs, such as perceived barriers, perceived severity, perceived susceptibility, self-efficacy, and perceived benefit influence prevention practices. Lastly, only 23 articles (40.3%) had piloted or pretested the questionnaire before surveying, in which three reported Cronbach’s alpha coefficient (0.70–0.90). A need for active participation of communities and healthcare personnel, promotion of awareness, and safe complementary medicines, as well as assessment of psychometric properties of questionnaire use in dengue surveys in Malaysia, in order for assessing dengue reliably and valid

Different domains of dengue research in the Philippines: A systematic review and meta- analysis of questionnaire-based studies

Dengue is the most rapidly spreading mosquito-borne viral disease of humans worldwide, including southeast Asia region. This review provides a comprehensive overview of questionnaire-related dengue studies conducted in the Philippines and evaluates their reliability and validity in these surveys. A review protocol constructed by a panel of experienced academic reviewers was used to formulate the methodology, research design, search strategy and selection criteria. An extensive literature search was conducted between March–June 2020 in various major electronic biomedical databases including PubMed, EMBASE, MEDLINE and ScienceDirect. A systematic review and meta-analysis (PRISMA) were selected as the preferred item reporting method. Out of a total of 34 peer-reviewed dengue-related KAP studies that were identified, 15 published from 2000 to April 2020 met the inclusion criteria. Based on the meta-analysis, a poor mean score was obtained for each of knowledge (68.89), attitude (49.86) and preventive practice (64.69). Most respondents were equipped with a good knowledge of the major clinical signs of dengue. Worryingly, 95% of respondents showed several negative attitudes towards dengue prevention, claiming that this was not possible and that enacting preventive practices was not their responsibility. Interestingly, television or radio was claimed as the main source of gaining dengue information (range 50–95%). Lastly, only five articles (33.3%) piloted or pretested their questionnaire before surveying, of which three reported Cronbach’s alpha coefficient (range 0.70 to 0.90). This review indicates that to combat the growing public health threat of dengue to the Philippines, we need the active participation of resident communities, full engagement of healthcare personnel, promotion of awareness campaigns, and access to safe complementary and alternative medicines. Importantly, the psychometric properties of each questionnaire should be assessed rigorously

Molecular regulatory roles of long non-coding RNA HOTTIP: An overview in gastrointestinal cancers

Gastrointestinal (GI) cancers presented an alarmingly high number of new cancer cases worldwide and are highly characterised by poor prognosis. The poor overall survival is mainly due to late detection and emerging challenges in treatment, particularly chemoresistance. Thus, the identification of novel molecular targets in GI cancer is highly regarded as the main focus. Recently, long non-coding RNAs (lncRNAs) have been discovered as potential novel molecular targets for combating cancer, as they are highly associated with carcinogenesis and have a great impact on cancer progression. Amongst lncRNAs, HOTTIP has demonstrated a prominent oncogenic regulation in cancer progression, particularly in GI cancers, including oesophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. This review aimed to present a focused update on the regulatory roles of HOTTIP in GI cancer progression and chemoresistance, as well as deciphering the associated molecular mechanisms underlying their impact on cancer phenotypes and chemoresistance and the key molecules involved. It has been reported that it regulates the expression of various genes and proteins in GI cancers that impact cellular functions, including proliferation, adhesion, migration and invasion, apoptosis, chemosensitivity, and tumour differentiation. Furthermore, HOTTIP was also discovered to have a higher diagnostic value as compared to existing diagnostic biomarkers. Overall, HOTTIP has presented itself as a novel therapeutic target and potential diagnostic biomarker in the development of GI cancer treatment

Molecular Targets of Aptamers in Gastrointestinal Cancers: Cancer Detection, Therapeutic Applications, and Associated Mechanisms

Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers’ generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications

Matrix metalloproteinases in chemoresistance: regulatory roles, molecular interactions, and potential inhibitors

Cancer is one of the major causes of death worldwide. Its treatments usually fail when the tumor has become malignant and metastasized. Metastasis is a key source of cancer recurrence, which often leads to resistance towards chemotherapeutic agents. Hence, most cancer-related deaths are linked to the occurrence of chemoresistance. Although chemoresistance can emerge through a multitude of mechanisms, chemoresistance and metastasis share a similar pathway, which is an epithelial-to-mesenchymal transition (EMT). Matrix metalloproteinases (MMPs), a class of zinc and calcium-chelated enzymes, are found to be key players in driving cancer migration and metastasis through EMT induction. The aim of this review is to discuss the regulatory roles and associated molecular mechanisms of specific MMPs in regulating chemoresistance, particularly EMT initiation and resistance to apoptosis. A brief presentation on their potential diagnostic and prognostic values was also deciphered. It also aimed to describe existing MMP inhibitors and the potential of utilizing other strategies to inhibit MMPs to reduce chemoresistance, such as upstream inhibition of MMP expressions and MMP-responsive nanomaterials to deliver drugs as well as epigenetic regulations. Hence, manipulation of MMP expression can be a powerful tool to aid in treating patients with chemo-resistant cancers. However, much still needs to be done to bring the solution from bench to bedside

Behavioural and molecular study of methamphetamine use and addiction in a rat model /Sim Maw Shin

Methamphetamine (METH) is a highly addictive psycho-stimulant that induces behavioral changes, most likely due to high level of METH-induced dopamine in the brain. Nucleus accumbens (NAc) and hippocampus are the critical part of the brain in which the changes occur in drug addiction. However, little is known about the underlying molecular mechanisms of METH-induced addiction on miRNA, transcriptome and protein expression. The main objectives of this study are to study the behavioral changes that occur with use and addiction to METH and to determine the global miRNA, transcriptome and protein profiling in the NAc and hippocampus of METH-addicted rats, and also to identify miRNAs, genes and proteins which are associated with METH exposure and addiction. The experimental rats were divided into 3 groups of 6 each: a control group, a single dose METH (5 mg/kg, i.p.) treatment group and a continuous 15 alternate days METH (0.25, 0.5, 1, 2, 3, 4, 5 mg/kg) treatment group. Addiction behavior in rats was determined using Conditioned Place Preference (CPP) task. The analysis of the miRNA and transcriptome profiling in the NAc and hippocampus was performed using Affymetric microarray GeneChip® System, while the protein profiling was performed using Thermo Scientific LTQ Orbitrap mass spectrometer. The results of the study showed that the continuous 15 alternate days METH treatment rats showed a preference for the drug-paired compartment of the CPP. However, a one-time acute treatment with 5 mg/kg METH did not show any significant difference in preference when compared with the control group. Addiction behavior was only seen when rats consumed increasing doses of METH over a continuous exposure period. We also found that the continuous exposure with administration of increasing doses may reduce the learning and memory ability in rats. Differential molecular profiling indicated that 170 miRNAs, 3 genes and 15 proteins were up-regulated, while iv 4 miRNAs, 26 genes and 27 proteins were down-regulated in the NAc when the continuous METH treatment group was compared with the controls. In comparing the METH addiction group (continuous treatment) with the non-addiction group (acute treatment), 38 miRNAs, 6 genes and 25 proteins were shown to be up-regulated and 4 miRNAs, 32 genes and 15 proteins were down-regulated. In the hippocampus, 180 miRNAs, 8 genes and 28 proteins were up-regulated, while 10 miRNAs, 13 genes and 5 proteins were down-regulated when the continuous treatment group was compared with the controls. In comparing the addiction group with those without addiction, 104 miRNAs, 10 genes and 33 proteins were shown to be up-regulated and 5 miRNAs, 20 genes and 20 proteins were down-regulated. The level of significance applied was when changes were more than two fold change and with ANOVA and FDR test with p<0.05. Our results suggest that the rat model that has been developed is adequate as an addiction behavior model for METH, and that dynamic changes occur in the expression of mRNAs, miRNAs and proteins with METH exposure and addiction

Psychosocial risk factors associated with lifetime Amphetamine-Type Stimulants (ATS) dependence in Drug Detention Centres: perspectives from the multiethnicity study.

ATS dependence in Malaysia is growing tremendously across multiracial Malaysian groups, increasing concerns among public health experts and the community. This study highlighted the chronicity of ATS dependence and factors associated with ATS use. Interviewer-administered questionnaires were administered using ASSIST 3.0. A total of N = 327 multiracial people who use ATS were enrolled in this study. The study findings show that 190/327 (58.1%) respondents were ATS dependent. Malays reported the highest number of ATS-dependent (55.8%), followed by Bajau (21.6%) and Kadazan-Dusun (16.8%) ethnic. Across all races, three factors were significantly associated with the ATS dependence: respondents who had a lifetime history of needle sharing aOR = 0.023 (95% CI: 0.003, 0.183) and a lifetime history of heroin use aOR = 0.192 (95% CI: 0.093, 0.396) were at a reduced odd of ATS dependent. Meanwhile, being married reduced the likelihood of becoming dependent on ATS with aOR = 0.378 (95% CI: 0.206, 0.693) compared to being single or divorced. This study revealed that the use of ATS among multiracial Malaysians is alarmingly high, including those in detention centers. Comprehensive harm reduction strategies are urgently needed to prevent the spreading of infectious diseases and other negative health consequences associated with ATS use