Differential expression of six cytokines in Rattus rattus exposed to leptospirosis: A comprehensive transcriptomic analysis.

Background: Rattus rattus are the main carriers of various zoonotic diseases including leptospirosis. Regrettably, information underlying the cytokine response of wild R. rattus upon leptospirosis infection is lacking.

Cost-effectiveness analysis of biologic sequential treatments for moderate-to-severe psoriasis: A Malaysian healthcare system perspective.

Objective: In Malaysia, there is now a dearth of recommendations pertaining to the priority of biologic treatments for the effective management of psoriasis, given the multitude of available therapeutic alternatives. Present analysis reports results of a cost-effectiveness model that determines the most optimal arrangement of biologic treatments, with a particular focus of adding biosimilars to the existing treatment pathway for psoriasis in Malaysia.

Methods: A Markov model was developed to compare the cost effectiveness of various biologic sequential treatments in a hypothetical cohort of moderate to severe psoriasis patient in Malaysia over a lifetime horizon.

A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation.

Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients.

Targeted Isolation of Antiviral Labdane Diterpenes from the Bark of (Annonaceae) using LC-MS/MS-Based Molecular Networking.

In the search of new inhibitors for human coronavirus (HCoV), we screened extracts of endemic Annonaceae plants on an assay using a cellular model of Huh-7 cells infected with the human alphacoronavirus HCoV-229E. The EtOAc bark extract of the rare Southeast Asian plant exhibited inhibition of HCoV-229E and SARS-CoV-2 viruses with IC values of 3.8 and 7.

Synthesis of 2,4-dihydroxyacetophenone derivatives as potent PDE-1 and -3 inhibitors: and insights.

Synthesis of novel -Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. -Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their PDE-1 and -3 inhibitory activities.

Novel hydrazone schiff's base derivatives of polyhydroquinoline: synthesis, prolyl oligopeptidase inhibitory activity and their Molecular docking study.

This research work reports the synthesis of new derivatives of the hydrazone Schiff bases () based on polyhydroquinoline nucleus through multistep reactions. HR-ESIMS,H- and C-NMR spectroscopy were used to structurally infer all of the synthesized compounds and lastly evaluated for prolyl oligopeptidase inhibitory activity. All the prepared products displayed good to excellent inhibitory activity when compared with standard z-prolyl-prolinal.

Enhancing tuberculosis treatment adherence and motivation through gamified real-time mobile app utilization: a single-arm intervention study.

Background: Finding innovative methods to enhance Tuberculosis treatment adherence in Malaysia is imperative, given the rising trend of non-adhere TB patients. Direct Observed Therapy (DOTS) has been used to ensure Tuberculosis (TB) drug compliance worldwide. However, due to its inconvenience, digitalizing this system into a virtual monitoring system via a mobile app can help deliver a more efficient tuberculosis management system.

Determining the Willingness to Pay for Innovative Oncology Medicines in Malaysia.

Objectives: Early access to innovative oncology medicine is crucial to provide better treatment alternatives to patients with cancer. However, innovative oncology medicines often come at higher prices, thus limiting the government's ability for its universal coverage. Hence an alternative paying mechanism is needed.

In vitro evaluation of cytotoxicity and genotoxicity of porous nickel titanium dental implants produced by metal injection molding technique.

Porous NiTi (pNiTi) is a promising biomaterial for functional long-term implantation that has been produced using various manufacturing techniques and tested for biocompatibility. pNiTi produced using a more recent technology of Metal Injection Molding (MIM) has shown better physical and mechanical properties than those produced by earlier manufacturing methods, but its biocompatibility has yet to be determined. Hence, extracts from pNiTi dental implants produced by MIM were tested for cytotoxicity and genotoxicity in this work.

A Gamified Real-time Video Observed Therapies (GRVOTS) Mobile App via the Modified Nominal Group Technique: Development and Validation Study.

Background: The success rate of tuberculosis (TB) treatment in Malaysia remains below the recommended World Health Organization target of 90% despite the implementation of directly observed therapy, short-course, a physical drug monitoring system, since 1994. With increasing numbers of patients with TB in Malaysia defaulting on treatment, exploring another method to improve TB treatment adherence is vital. The use of gamification and real-time elements via video-observed therapies in mobile apps is one such method expected to induce motivation toward TB treatment adherence.

Correlation of chemical profiles obtained from H-NMR and LC-MS metabolomics with α-glucosidase inhibition activity for varietal selections of Ficus deltoidea.

Introduction: Ficus deltoidea Jack (Moraceae) is a plant used in Malaysia to treat various ailments, including diabetes. The presence of several varieties raises essential questions regarding which is the potential bioactive variety and what are the bioactive metabolites.

Objectives: Here, we explored the phytochemical diversity of the seven varieties from Peninsular Malaysia using Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS) analyses and correlated it with the α-glucosidase inhibitory activity.

Effects of Concurrent Tasks on Gait Performance in Children With Traumatic Brain Injury Versus Children With Typical Development.

Objective: To investigate how gait parameters in children with traumatic brain injury (TBI) versus typically developing (TD) children are influenced by secondary concurrent tasks and examine the correlations between gait parameters and attention and balance in children with TBI.

Methods: Sixteen children with TBI (mean age, 11.63±1.

Biocatalytic modifications of ethynodiol diacetate by fungi, anti-proliferative activity, and acetylcholineterase inhibitory of its transformed products.

The fungal transformations of ethynodiol diacetate (1) were investigated for the first-time using Botrytis cinerea, Trichothecium roseum, and R3-2 SP 17. The metabolites obtained are as following: 17α-Ethynyl-17β-acetoxyestr-4-en-3-one-15β-ol (2), 19-nor-17a-ethynyltestosterone (3), and 17α-ethynyl-3β-hydroxy-17β-acetoxyestr-4-ene (4). The new metabolite, 2 (IC = 104.

Medroxyprogesterone derivatives from microbial transformation as anti-proliferative agents and acetylcholineterase inhibitors (combined in vitro and in silico approaches).

The fungal transformations of medroxyrogesterone (1) were investigated for the first time using Cunninghamella elegans, Trichothecium roseum, and Mucor plumbeus. The metabolites obtained are as following: 6β, 20-dihydroxymedroxyprogesterone (2), 12β-hydroxymedroxyprogesterone (3), 6β, 11β-dihydroxymedroxyprogesterone (4), 16β-hydroxymedroxyprogesterone (5), 11α, 17-dihydroxy-6α-methylpregn-4-ene-3, 20-dione (6), 11-oxo-medroxyprogesterone (7), 6α-methyl-17α-hydroxypregn-1,4-diene-3,20-dione (8), and 6β-hydroxymedroxyprogesterone (9), 15β-hydroxymedroxyprogesterone (10), 6α-methyl-17α, 11β-dihydroxy-5α-pregnan-3, 20-dione (11), 11β-hydroxymedroxyprogesterone (12), and 11α, 20-dihydroxymedroxyprogesterone (13). Among all the microbial transformed products, the newly isolated biotransformed product 13 showed the most potent activity against proliferation of SH-SY5Y cells.

Appropriateness of empirical antibiotics: risk factors of adult patients with sepsis in the ICU.

Background The appropriateness of antibiotics is the basis for improving the survival of patients with sepsis. Objective This study aimed to determine the appropriateness of empirical antibiotics, reasons for non-appropriate empirical antibiotics, risk factors of mortality, length of stay in intensive care unit (ICU-LOS) and Acute Physiology And Chronic Health Evaluation II (APACHE II) score predictors in adult patients with sepsis. Setting An adult ICU of a tertiary hospital in  Malaysia.

Synthesis of Novel Triazinoindole-Based Thiourea Hybrid: A Study on α-Glucosidase Inhibitors and Their Molecular Docking.

A new class of triazinoindole-bearing thiosemicarbazides (-) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogs exhibited excellent inhibitory potential, with IC values ranging from 1.30 ± 0.

Synthesis of Chromen-4-One-Oxadiazole Substituted Analogs as Potent -Glucuronidase Inhibitors.

Chromen-4-one substituted oxadiazole analogs - have been synthesized, characterized and evaluated for -glucuronidase inhibition. All analogs exhibited a variable degree of -glucuronidase inhibitory activity with IC values ranging in between 0.8 ± 0.

Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study.

We have synthesized quinoxaline analogs (⁻), characterized by ¹H-NMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC = 38.68 ± 4.

Laevifins A-G, clerodane diterpenoids from the Bark of Croton oblongus Burm.f.

A phytochemical investigation of the stem barks of the Malaysian Croton oblongus Burm.f. (Syn.

Protective effects of seed extract on lead induced neurotoxicity during development and early life in mouse models.

Lead (Pb), a ubiquitous heavy metal and a known neurotoxicant, produces adverse effects on the brain increased production of reactive oxygen species (ROS) and causes oxidative stress. In this study we examined the neuroprotective effects of the ethanolic extract of seeds on Pb induced oxidative stress in the developing brain of mice. Mouse pups were exposed to low (0.

Neuroprotective effects of Foeniculum vulgare seeds extract on lead-induced neurotoxicity in mice brain.

The present study investigates the neuroprotective effects of Foeniculum vulgare seeds in a lead (Pb)-induced brain neurotoxicity mice model. The dried seeds extract of Foeniculum vulgare was prepared with different concentrations of organic solvents (ethanol, methanol, n-hexane). The in vitro antioxidant activity of Foeniculum vulgare seed extracts was assessed through DPPH assay and the chemical composition of the extracts was determined by high-resolution H NMR spectroscopy.

Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors.

Three new norditerpenoids alkaloids, 1β-hydroxy,14β-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, H and C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies.

Exposure to Electrophiles Impairs Reactive Persulfide-Dependent Redox Signaling in Neuronal Cells.

Electrophiles such as methylmercury (MeHg) affect cellular functions by covalent modification with endogenous thiols. Reactive persulfide species were recently reported to mediate antioxidant responses and redox signaling because of their strong nucleophilicity. In this study, we used MeHg as an environmental electrophile and found that exposure of cells to the exogenous electrophile elevated intracellular concentrations of the endogenous electrophilic molecule 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), accompanied by depletion of reactive persulfide species and 8-SH-cGMP which is a metabolite of 8-nitro-cGMP.

Effects of Kinesio Taping on Dynamic Balance Following Fatigue: a Randomized Controlled Trial.

The objective of the study was to determine the effects of Kinesio taping (KT) in inhibiting fatigue and preserving dynamic balance. Male recreational athletes were recruited to participate in this study. Participants were blinded from the group assignment and divided into four groups (Group A; KT and fatigue, Group B; no tape and fatigue, Group C; KT and no fatigue and Group D; no tape and no fatigue) using sequentially opaque, sealed envelopes.

Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats.

Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats.