Emergence of taurine as a therapeutic agent for neurological disorders

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the body.It alternates between inflammation and oxidative stress-mediated injury in various disease models.As part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular level.Taurine effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord injury.Although various therapies are available,effective management of these disorders remains a global challenge.Approximately 30 million people are affected worldwide.The design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders.The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review.This article is a good resource for understanding the general effects of taurine on various diseases.Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

Clonal distribution and possible micro evolution of methicillin-resistant Staphylococcus aureus strains in a teaching hospital in Malaysia

Objective:To genotypically characterize methicillin-resistant Staphylococcus aureus(MRSA)strains isolated from medical and surgical wards in Universiti Kebangsaan Malaysia Medical Centre(UKMMC)in 2009.Methods:MRSA strains were collected and molecularly typed by pulsed-field gel electrophoresis(PFGE).Results:PFGE typing on 180 MRSA isolated in UKMMC identified 5 pulsotypes(A-E)and 6 singletons,where pulsotypes B and C were suspected to he divergent clones originating from a single ancestor.This study also showed that most MRSA strains were isolated from swab(119 isolates),followed by blood(22 isolates),tracheal aspirate(11isolates)and sputum(10 isolates).On the other hand,urine and bone isolates were less,which were 4 and 1 isolates,respectively.The distribution of different pulsotypes of MRSA among wards suggested that MRSA was communicated in surgical and medical wards in UKMMC,with pulsotype B MRSA as the dominant strain.Besides,it was found that most deceased patients were infected by pulsotype B MRSA,however,no particular pulsotype could be associated with patient age,underlying disease,or ward of admittance.Conclusions:Five pulsotypes of MRSA and 6singletons were identified,with pulsotype B MRSA as the endemic strains circulating in these wards,which is useful in establishment of preventive measures against MRSA transmission.

Cardiovascular Disease Prediction Among the Malaysian Cohort Participants Using Electrocardiogram

A comprehensive study was conducted to differentiate cardiovascular disease (CVD) subjects from non-CVD subjects using short recording electrocardiogram (ECG) of 244 Malaysian adults in The MalaysianCohort project. An automated peak detection algorithm to detect nine fiducialpoints of electrocardiogram (ECG) was developed. Forty-eight features wereextracted in both time and frequency domains, including statistical featuresobtained from heart rate variability and Poincare plot analysis. These includefive new features derived from spectrum counts of five different frequencyranges. Feature selection was then made based on p-value and correlationmatrix. Selected features were used as input for five classifiers of artificialneural network (ANN), k-nearest neighbors (kNN), support vector machine(SVM), discriminant analysis (DA), and decision tree (DT). Results showedthat six features related to T wave were statistically significant in distinguishingCVD and non-CVD groups. ANN had performed the best with 94.44% specificity and 86.3% accuracy, followed by kNN with 80.56% specificity, 86.49%sensitivity and 83.56% accuracy. The novelties of this study were in providingalternative solutions to detect P-onset, P-offset, T-offset as well as QRS-onsetpoints using discrete wavelet transform method. Additionally, two out of thefive newly proposed spectral features were significant in differentiating bothgroups, at frequency ranges of 1–10 Hz and 5–10 Hz. The prediction outcomeswere also comparable to previous related studies and significantly importantin using ECG to predict cardiac-related events among CVD and non-CVDsubjects in the Malaysian population.

Astragalus Polysaccharide Enhances Voriconazole Metabolism under Inflammatory Conditions through the Gut Microbiota

Background and Aims:Voriconazole(VRC),a widely used antifungal drug,often causes hepatotoxicity,which presents a significant clinical challenge.Previous studies demonstrated that Astragalus polysaccharide(APS)can regulate VRC metabolism,thereby potentially mitigating its hepatotoxic effects.In this study,we aimed to explore the mechanism by which APS regulates VRC metabolism.Methods:First,we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale.Second,we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism.Various in vitro and in vivo assays,including cytokine profiling,immunohistochemistry,quantitative polymerase chain reaction,metabolite analysis,and drug concentration measurements,were performed using a lipopolysaccharideinduced rat inflammation model.Finally,experiments such as intestinal biodiversity analysis,intestinal clearance assessments,and Bifidobacterium bifidum replenishment were performed to examine the ability of B.bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut–liver axis.Results:The results indicated that APS does not have a direct effect on hepatocytes.However,the assessment of gut microbiota function revealed that APS significantly increases the abundance of B.bifidum,which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism.The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-κB signaling pathway.Conclusions:The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage,highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells

Objective： The combination effect of Piperbetle （PB） and 5-fluorouracil （5-FU） in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods： HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography （HPLC） was performed to exclude any possible chemical interaction between the compounds. Results： In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose （IC^0 12.5 pmol/L） and a shorter time （24 h） in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively. Conclusions： In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.

Current status of serum metabolites biomarkers for polyps and colorectal cancer:a systematic review

Background:Early detection of colorectal cancer(CRC)is crucial to enhance the disease treatment and prognosis of patients.Colonoscopy remains the gold standard for CRC detection;however,it requires trained personnel with expensive tools.Currently,serum metabolites have been discovered to be used to discriminate patients with polyps and CRC.This study aimed to identify the most commonly detected predictive serum metabolites for polyps and CRC.Methods:A systematic search of the Web of Science,PubMed,and Cochrane Library databases was conducted using PRISMA guidelines.Ten studies investigating serum metabolite biomarkers of CRC and polyps using different analytical platforms and study populations were included.QUADOMICS tool was used to analyse the quality of the included studies.All reported metabolites were then enriched into the pathways using MetaboAnalyst 5.0.Results:We found that several potential signature metabolites overlapped between studies,including tyrosine,lysine,cystine,arabinose,and lactate for CRC and lactate and glutamate for polyps.The most affected pathways related to CRC were the urea cycle,glutathione metabolism,purine metabolism,glutamate metabolism,and ammonia recycling.In contrast,those affected in the polyps were the urea cycle,glutamate metabolism,glutathione metabolism,arginine and proline metabolism,and carnitine synthesis.Conclusions:This review has found commonly detected serum metabolites for polyps and CRC with huge potential to be used in clinical settings.However,the differences between altered pathways in polyps and CRC,other external factors,and their effects on the regulation level,sensitivity,and specificity of each identified metabolite remained unclear,which could benefit from a further extensive cohort study and well-defined analysis equipment.