Role of cell surface proteins and toll-like receptors in the pathogenesis of Streptococcus pneumoniae.

Objectives: Pneumococcal cell wall (PCW) is an inflammatory component in Streptococcus pneumoniae. The cell surface proteins and the toll-like receptors (TLR) signaling response were investigated in the human lung epithelial (A549) cells inoculated with PCW of different serotypes. Materials and Methods: The presence of genes encoding these proteins was determined using polymerase chain reaction (PCR). The structure of the cell walls was analyzed by proton nuclear magnetic resonance (1H NMR). The A549 cell line was challenged with PCW extracts of different serotypes. RNA from the infected host cells was extracted and tested against a total of 84 genes associated with TLR signaling pathways (TLR 1-6 and 10) using RT2 Profiler PCR Array. Results: Cell surface proteins; ply, lytA, nanA, nanB, and cbpD genes were present in all serotypes. The distribution and structure of surface protein genes suggest behavioral changes in the molecules, contributing to the resilience of the strains to antibiotic treatment. Conclusion: TLR2 showed the highest expression, while serotypes 1, 3, and 5 induced higher TNFα and IL-1α, suggesting to be more immunogenic than the other strains tested.

Naturally Occurring Phytochemicals to Target Breast Cancer Cell Signaling.

Almost 70% of clinically used antineoplastic drugs are originated from natural products such as plants, marine organism, and microorganisms and some of them are also structurally modified natural products. The naturally occurring drugs may specifically act as inducers of selective cytotoxicity, anti-metastatic, anti-mutagenic, anti-angiogenesis, antioxidant accelerators, apoptosis inducers, autophagy inducers, and cell cycle inhibitors in cancer therapy. Precisely, several reports have demonstrated the involvement of naturally occurring anti-breast cancer drugs in regulating the expression of oncogenic and tumor suppressors associated with carcinogen metabolism and signaling pathways. Anticancer therapies based on nanotechnology have the potential to improve patient outcomes through targeted therapy, improved drug delivery, and combination therapies. This paper has reviewed the current treatment for breast cancer and the potential disadvantages of those therapies, besides the various mechanism used by naturally occurring phytochemicals to induce apoptosis in different types of breast cancer. Along with this, the contribution of nanotechnology in improving the effectiveness of anticancer drugs was also reviewed. With the development of sciences and technologies, phytochemicals derived from natural products are continuously discovered; however, the search for novel natural products as chemoprevention drugs is still ongoing, especially for the advanced stage of breast cancer. Continued research and development in this field hold great promise for advancing cancer care and improving patient outcomes.

Genotypic characteristics of Uropathogenic Escherichia coli isolated from complicated urinary tract infection (cUTI) and asymptomatic bacteriuria-a relational analysis.

Background: Uropathogenic Escherichia coli (UPEC) is the predominant agent causing various categories of complicated urinary tract infections (cUTI). Although existing data reveals that UPEC harboured numerous virulence determinants to aid its survival in the urinary tract, the reason behind the occurrence of differences in the clinical severity of uninary tract infections (UTI) demonstrated by the UPEC infection is poorly understood. Therefore, the present study aims to determine the distribution of virulence determinants and antimicrobial resistance among different phylogroups of UPEC isolated from various clinical categories of cUTI and asymptomatic bacteriuria (ASB) E. coli isolates. The study will also attempt a relational analysis of the genotypic characteristics of cUTI UPEC and ASB E. coli isolates. Methods: A total of 141 UPEC isolates from cUTI and 160 ASB E. coli isolates were obtained from Universiti Malaya Medical Centre (UMMC). Phylogrouping and the occurrence of virulence genes were investigated using polymerase chain reaction (PCR). Antimicrobial susceptibility of the isolates to different classes of antibiotics was determined using the Kirby Bauer Disc Diffusion method. Results: The cUTI isolates were distributed differentially among both Extraintestinal Pathogenic E. coli (ExPEC) and non-ExPEC phylogroups. Phylogroup B2 isolates were observed to possess the highest average aggregative virulence score (7.17), a probable representation of the capability to cause severe disease. Approximately 50% of the cUTI isolates tested in this study were multidrug resistant against common antibiotics used to treat UTI. Analysis of the occurrence of virulence genes among different cUTI categories demonstrated that UPEC isolates of pyelonephritis and urosepsis were highly virulent and had the highest average aggregative virulence scores of 7.80 and 6.89 respectively, compared to other clinical categories. Relational analysis of the occurrence of phylogroups and virulence determinants of UPEC and ASB E. coli isolates showed that 46.1% of UPEC and 34.3% of ASB E. coli from both categories were distributed in phylogroup B2 and had the highest average aggregative virulence score of 7.17 and 5.37, respectively. The data suggest that UPEC isolates which carry virulence genes from all four virulence genes groups studied (adhesions, iron uptake systems, toxins and capsule synthesis) and isolates from phylogroup B2 specifically could predispose to severe UTI involving the upper urinary tract. Therefore, specific analysis of the genotypic characteristics of UPEC could be further explored by incorporating the combination of virulence genes as a prognostic marker for predicting disease severity, in an attempt to propose a more evidence driven treatment decision-making for all UTI patients. This will go a long way in enhancing favourable therapeutic outcomes and reducing the antimicrobial resistance burden among UTI patients.

Metabolic Syndrome Screening and Nutritional Status of Patients with Psoriasis: A Scoping Review.

Background: Patients with plaque psoriasis have an increased risk of metabolic syndrome. However, no studies have assessed the nutritional status or screening methods of this population. Aims: This review aimed to identify and summarise metabolic syndrome screening criteria and the tools/methods used in nutrition assessment in patients with plaque psoriasis. Data synthesis: PubMed, Web of Science, Ovid and Scopus were searched from inception to March 2023, following the Arkensey and O'Malley framework, to identify articles that report nutritional assessment methods/tools and metabolic screening criteria. Twenty-one studies were identified. Overall, these studies used four different screening criteria to define metabolic syndrome. Patients with psoriasis had a high prevalence of metabolic syndrome and had a poor nutritional status compared to controls. However, only anthropometric measures such as weight, height and waist circumference were employed to determine the nutritional status. Only two studies assessed the vitamin D status. Conclusions: Patients with psoriasis have a poor nutritional status, and they are at risk of nutrient deficiencies. However, these health aspects are not routinely assessed and may increase the risk of malnutrition among these patients. Therefore, additional assessments, such as body composition and dietary assessment, are needed to determine the nutritional status to provide a suitable intervention.

Association between vision and cognitive function among community-dwelling older adults in Selangor, Malaysia.

AIM: To determine the association between distance and near visual acuity (VA) and cognitive function among older adults in Selangor, Malaysia. METHODS: A total of 230 older adults (age ≥60y) participated in this study. Habitual distance and near VA were measured using the Early Treatment Diabetic Retinopathy Study Chart and Lighthouse Near Visual Acuity Chart, respectively. Global cognitive function was assessed using the Mini-Mental State Examination (M-MSE) and the Malay language version of the Montreal Cognitive Assessment (M-MoCA). Digit Symbol (DS) subtest was used to measure information processing. RESULTS: No significant association was observed between vision and M-MSE and M-MoCA scores. However, poor distance and near VA were found to be significantly associated with low DS scores [distance VA: ß=-0.01, R 2=0.1, P=0.02; odds ratio (OR)=2.84, 95% confidence interval (CI), 1.10-7.33, P=0.03; near VA: ß=-0.05, R 2=0.08, P=0.00; OR=3.32, 95%CI, 1.28-8.59, P=0.01]. CONCLUSION: Poor vision is associated with a decline in information processing in older adults and substantiates the importance of preserving good vision in maintaining cognitive function.

Knowledge and Compliance among Contact Lens Wearers Living in Kuala Lumpur, Malaysia: A Cross-Sectional Study.

Background: Many factors determine the success of wearing contact lens, including knowledge and compliance towards lens care. This study aimed to evaluate the level of knowledge and compliance between two groups of adult contact lens wearers in Kuala Lumpur, Malaysia. Methods: A total of 60 participants aged 18-30 years old volunteered to participate in this study (30 participants prescribed contact lenses at the Universiti Kebangsaan Malaysia [UKM] optometry clinic and 30 participants fitted at private practices). Participants were interviewed using a structured questionnaire consisting of nine questions on basic knowledge related to lens wear and 13 questions on compliance, categorised into questions on the cleaning process, disinfection, accessories care and replacement schedule. Results: All participants wore disposable contact lens 53.3% (n = 32) participants preferred using monthly disposable lenses. Both groups had the same level of knowledge, except knowledge of the effects of makeup (P < 0.000) and duration of the solution used for cleaning (P < 0.010), showing lack of knowledge on contact lenses among participants in private practices group. There were no significant differences between the groups in terms of the level of compliance with the cleaning process (P = 0.830), disinfection (P = 0.725), accessories care (P = 0.865) and replacement schedule (P = 0.699). Conclusion: Participants from UKM optometry clinic had better knowledge on wearing contact lens; moreover, both groups had good compliance towards lens care. Contact lens practitioners should provide all the necessary information to contact lens wearers so that they are equipped to handle contact lenses correctly, which would minimise the risk of eye complications.

Evaluation of Antimicrobial and Antibiofilm Activity of Citrus medica Fruit Juice Based Carbon Dots against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is one of the common immortal pathogens that cause intense chronic infections in low-immunity patients, significantly evading the immune system and suppressing the respiratory system. This work reports on the synthesis of prominent members of the carbon family, carbon quantum dots (CQDs), from a natural carbon precursor, Citrus medica (C. medica) fruit, and their inhibiting property against P. aeruginosa. CQDs synthesized by the conventional hydrothermal method with an average particle size of 4.5 nm exhibit renowned antimicrobial properties. To enhance the properties of the CQDs, nitrogen was doped using ammonium hydroxide as a nitrogen source, and absorption and fluorescence studies and the elemental composition of CQDs were also reported. CQDs potentially inhibited the growth of bacteria at the lowest concentration level of 1.25% (v/v). Similarly, CQDs moderately inhibited biofilm formation at the concentration level of 0.07% (v/v) for both clinical and control strains of P. aeruginosa. A fluorescence microscopy study revealed that the treated strain shows a moderately reduced biofilm formation when compared to the control strain of P. aeruginosa PAO1.

In Silico Evaluation of Bioactive Compounds of Artemisia pallens Targeting the Efflux Protein of Multidrug-Resistant Acinetobacter baumannii (LAC-4 Strain).

Acinetobacter baumannii (A. baumannii) is one of the major representative aetiologies of recalcitrant nosocomial infections. Genotypic and phenotypic alterations in A. baumannii have resulted in a significant surge in multidrug resistance (MDR). Of all the factors responsible for the development of antimicrobial resistance (AMR), efflux protein pumps play a paramount role. In pursuit of a safe alternative for the prevention and control of A. baumannii infections, bioactive compounds from the aerial parts of the medicinal plant Artemisia pallens were studied. GC-MS analysis of the ethanol extract of A. pallens detected five major compounds: lilac alcohol A, spathulenol, lilac alcohol C, n-hexadecanoic acid, and vulgarin. In silico examinations were performed using the Schrödinger suite. Homology modelling was performed to predict the structure of the efflux protein of A. baumannii-LAC-4 strain (MDR Ab-EP). The identified bioactive compounds were analysed for their binding efficiency with MDR Ab-EP. High binding efficiency was observed with vulgarin with a glide score of -4.775 kcal/mol and stereoisomers of lilac alcohol A (-3.706 kcal/mol) and lilac alcohol C (-3.706 kcal/mol). Our molecular dynamic simulation studies unveiled the stability of the ligand-efflux protein complex. Vulgarin and lilac alcohol A possessed strong and stable binding efficiency with MDR Ab-EP. Furthermore, validation of the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the ligands strongly suggested that these compounds could serve as a lead molecule in the development of an alternate drug from A. pallens.

Genotypic and phenotypic characterization of Escherichia coli isolated from indigenous individuals in Malaysia.

Objectives: The occurrence of asymptomatic verocytotoxin (VT)-producing Escherichia coli (VTEC) infections among humans in recent years is posing a high risk to public health. Thus, the role of asymptomatic human carriers as a source of dissemination should not be underestimated. This study aimed to elucidate the phenotypic and genotypic characteristics of E. coli in the stool samples collected from indigenous individuals in Malaysia. Materials and Methods: E. coli strains (n=108) were isolated from stool samples obtained from 41 indigenous individuals. All strains were subjected to Repetitive Extragenic Palindromic-Polymerase Chain Reaction (REP-PCR) typing and confirmation of VTEC variants. Non-duplicate strains were selected based on REP-PCR profiles and further subjected to antimicrobial susceptibility test (AST). The genotypic and phenotypic characteristics of the strains were then correlated with the demographic data of the subjects. Results: A total of 66 REP-PCR profiles grouped in 53 clusters (F=85%) were obtained. Four genetically distinct strains were confirmed as VTEC (eaeA-positive). The predominant resistance was against ampicillin (34.2%), followed by trimethoprim-sulfamethoxazole (32.9%), ampicillin-sulbactam (5.5%), and ciprofloxacin (1.4%). All isolates were sensitive to amoxicillin-clavulanate, cefuroxime, ceftriaxone, imipenem, and meropenem. Conclusion: Genetically diverse E. coli and VTEC strains were found to colonize the intestines of the indigenous populations. This study is important for the prospective surveillance of E. coli among the indigenous individuals in Malaysia, especially in asymptomatic VTEC infection and antimicrobial resistance phenomenon.

Biofilm-Associated Agr and Sar Quorum Sensing Systems of Staphylococcus aureus Are Inhibited by 3-Hydroxybenzoic Acid Derived from Illicium verum.

Biofilm-producing Staphylococcus aureus (S. aureus) is less sensitive to conventional antibiotics than free-living planktonic cells. Here, we evaluated the antibiofilm activity of Illicium verum (I. verum) and one of its constituent compounds 3-hydroxybenzoic acid (3-HBA) against multi-drug-resistant S. aureus. We performed gas chromatography-mass spectroscopy (GC-MS) to identify the major constituents in the methanolic extract of I. verum. Ligand-receptor interactions were studied by molecular docking, and in vitro investigations were performed using crystal violet assay, spreading assay, hemolysis, proteolytic activity, and growth curve analysis. The methanolic extract of I. verum inhibited S. aureus at 4.8 mg/mL, and GC-MS analysis revealed anethole, m-methoxybenzaldehyde, and 3-HBA as the major constituents. Molecular docking attributed the antibiofilm activity to an active ligand present in 3-HBA, which strongly interacted with the active site residues of AgrA and SarA of S. aureus. At a subinhibitory concentration of 2.4 mg/mL, the extract showed biofilm inhibition. Similarly, 3-HBA inhibited biofilm activity at 25 µg/mL (90.34%), 12.5 µg/mL (77.21%), and 6.25 µg/mL (62.69%) concentrations. Marked attrition in bacterial spreading was observed at 2.4 mg/mL (crude extract) and 25 µg/mL (3-HBA) concentrations. The methanol extract of I. verum and 3-HBA markedly inhibited ß-hemolytic and proteolytic activities of S. aureus. At the lowest concentration, the I. verum extract (2.4 mg/mL) and 3-HBA (25 µg/mL) did not inhibit bacterial growth. Optical microscopy and SEM analysis confirmed that I. verum and 3-HBA significantly reduced biofilm dispersion without disturbing bacterial growth. Together, we found that the antibiofilm activity of I. verum and 3-HBA strongly targeted the Agr and Sar systems of S. aureus.

Effect of Cryopreservation Method Supported with Biochemical Analyses in the Axillary Bud of Jewel Orchid, Ludisia discolor.

This study investigated conserving an endangered terrestrial jewel orchid Ludisia discolor, using in vitro grown axillary buds. Excised segments of axillary buds (4-5 mm in length) were precultured on a modified Murashige and Skoog (MS) medium supplemented with 0.2 M sucrose for 24 h and osmoprotected in a loading solution for 20 min. Then, axillary buds were dehydrated in plant vitrification solution 2 (PVS2) for 10 min at 0 °C and incubated in liquid nitrogen for 1 h. Subsequently, axillary buds were rewarmed rapidly by dilution solution and transferred to a growth recovery medium supplemented with 0.05 µM melatonin, which led to an improved survival chance (16.67%) for cryopreserved L. discolor. The osmotic stress and the overproduction of reactive oxygen species (ROS) during cryopreservation stages may result in cryoinjuries and poor survival as increased levels of proline (5.51 µmol/g), catalase (85.64 U/g), peroxidase (565.37 U/g), and ascorbate peroxidase activities (12.19 U/g) were detected after dehydration, preculture, rewarming, and loading stage, respectively. Results obtained from this study indicate that further experimental designs which apply different PVS and exogenous antioxidants are needed for improved survival and regrowth of L. discolor.

One Health surveillance approaches for melioidosis and glanders: The Malaysian perspective.

The One Health concept was initiated to promote the integration of human, animal, and environmental ecosystems into healthcare to ensure effective control and the sustainable governance of multifaceted health matters. Climate change, deforestation, and rigorous farming disrupt the environment, which serves as the natural habitat for many animals and microbes, increasing the likelihood of disease transmission between humans and animals. Melioidosis (neglected tropical diseases) and glanders are of humans and animals caused by the gram-negative bacteria Burkholderia pseudomallei and its close relative Burkholderia mallei, respectively. In Malaysia, although melioidosis is endemic, it is not a notifiable disease. Hence, the true prevalence of melioidosis in Malaysia is unknown and varies in different regions of the country, with reported hotspots associated with agriculture-related activities. To date, no incidence of human glanders has been reported in Malaysia, although occupational exposure for equine handlers and veterinary professionals remains a concern. Additionally, antibiotics are widely used in the healthcare and veterinary sectors to treat or prevent B. pseudomallei and B. mallei infections, leading to the emergence of resistance in B. pseudomallei. Lack of surveillance, research, assessment, and management of glanders and melioidosis is a major issue in Malaysia. Proper assessment systems and cross-discipline cooperation are vital to recognize and manage both diseases. Experts and practitioners from clinical and veterinary disciplines, environmentalists, law enforcement, policymakers, researchers, local communities, and other experts need to communicate, collaborate, and coordinate activities to fill the knowledge gap on glanders and melioidosis to reduce morbidity and mortality rates in the country. This review aims to define the organizational and functional characteristics of One Health surveillance approaches for glanders and melioidosis from a Malaysian perspective.

Overview of the distribution of Burkholderia pseudomallei sequence types and the Emergence of sequence type 1342 in Malaysia.

Burkholderia pseudomallei, a Gram-negative bacterial pathogen that causes melioidosis, is of public health importance in endemic areas including Malaysia. An investigation of the molecular epidemiology links of B. pseudomallei would contribute to better understanding of the clonal relationships, transmission dynamics and evolutionary change. Multilocus sequence typing (MLST) of 45 clinical B. pseudomallei isolates collected from sporadic melioidosis cases in Malaysia was performed. In addition, a total of 449 B. pseudomallei Malaysian strains submitted to the MLST database from 1964 until 2019 were included in the temporal analysis to determine the endemic sequence types (STs), emergence and re-emergence of ST(s). In addition, strain-specific distribution was evaluated using BURST tool. Genotyping of 45 clinical strains was resolved into 12 STs, and the majority were affiliated with ST46 (n = 11) and ST1342 (n = 7). Concomitantly, ST46 was the most prevalent ST in Malaysia, which was first reported in 1964. All the Malaysian B. pseudomallei strains were resolved into 76 different STs with 36 of them uniquely present only in Malaysia. ST1342 was most closely related to ST1034, in which both STs were unique to Malaysia and first isolated from soil samples in Pahang, a state in Malaysia. The present study revealed a high diversity of B. pseudomallei in Malaysia. Localized evolution giving rise to the emergence of new STs was observed, suggesting that host and environmental factors play a crucial role in the evolutionary changes in B. pseudomallei.

Role of Polyphenol in Regulating Oxidative Stress, Inflammation, Fibrosis, and Apoptosis in Diabetic Nephropathy.

Diabetic Nephropathy (DN) is known as one of the driving sources of End-Stage Renal Disease (ESRD). DN prevalence continues to increase in every corner of the world andthat has been a major concern to healthcare professionals as DN is the key driver of Diabetes Mellitus (DM) morbidity and mortality. Hyperglycaemia is closely connected with the production of Reactive Oxygen Species (ROS) that cause oxidative stress response as well as numerous cellular and molecular modifications. Oxidative stress is a significant causative factor to renal damage, as it can activate other immunological pathways, such as inflammatory, fibrosis, and apoptosis pathways. These pathways can lead to cellular impairment and death as well as cellular senescence. Natural substances containing bioactive compounds, such as polyphenols, have been reported to exert valuable effects on various pathological conditions, including DM. The role of polyphenols in alleviating DN conditions has been documented in many studies. In this review, the potential of polyphenols in ameliorating the progression of DN via modulation of oxidative stress, inflammation, fibrosis, and apoptosis, as well as cellular senescence, has been addressed. This information may be used as the strategies for the management of DN and development as nutraceutical products to overcome DN development.

Effective Therapeutic Options for Melioidosis: Antibiotics versus Phage Therapy.

Melioidosis, also known as Whitmore's disease, is a potentially fatal infection caused by the Gram-negative bacteria Burkholderia pseudomallei with a mortality rate of 10-50%. The condition is a "glanders-like" illness prevalent in Southeast Asian and Northern Australian regions and can affect humans, animals, and sometimes plants. Melioidosis received the epithet "the great mimicker" owing to its vast spectrum of non-specific clinical manifestations, such as localised abscesses, septicaemia, pneumonia, septic arthritis, osteomyelitis, and encephalomyelitis, which often lead to misdiagnosis and ineffective treatment. To date, antibiotics remain the backbone of melioidosis treatment, which includes intravenous therapy with ceftazidime or meropenem, followed by oral therapy with TMP-SMX or amoxicillin/clavulanic acid and supported by adjunctive treatment. However, bacteria have developed resistance to a series of antibiotics, including clinically significant ones, during treatment. Therefore, phage therapy has gained unprecedented interest and has been proposed as an alternative treatment. Although no effective phage therapy has been published, the findings of experimental phage therapies suggest that the concept could be feasible. This article reviews the benefits and limitations of antibiotics and phage therapy in terms of established regimens, bacterial resistance, host specificity, and biofilm degradation.

Genomic comparison and phenotypic profiling of small colony variants of Burkholderia pseudomallei.

Burkholderia pseudomallei (B. pseudomallei) is an intracellular pathogen that causes melioidosis, a life-threatening infection in humans. The bacterium is able to form small colony variants (SCVs) as part of the adaptive features in response to environmental stress. In this study, we characterize the genomic characteristics, antimicrobial resistance (AMR), and metabolic phenotypes of B. pseudomallei SCV and wild type (WT) strains. Whole-genome sequence analysis was performed to characterize the genomic features of two SCVs (CS and OS) and their respective parental WT strains (CB and OB). Phylogenetic relationship between the four draft genomes in this study and 19 publicly available genomes from various countries was determined. The four draft genomes showed a close phylogenetic relationship with other genomes from Southeast Asia. Broth microdilution and phenotype microarray were conducted to determine the AMR profiles and metabolic features (carbon utilization, osmolytes sensitivity, and pH conditions) of all strains. The SCV strains exhibited identical AMR phenotype with their parental WT strains. A limited number of AMR-conferring genes were identified in the B. pseudomallei genomes. The SCVs and their respective parental WT strains generally shared similar carbon-utilization profiles, except for D,L-carnitine (CS), g-hydroxybutyric acid (OS), and succinamic acid (OS) which were utilized by the SCVs only. No difference was observed in the osmolytes sensitivity of all strains. In comparison, WT strains were more resistant to alkaline condition, while SCVs showed variable growth responses at higher acidity. Overall, the genomes of the colony morphology variants of B. pseudomallei were largely identical, and the phenotypic variations observed among the different morphotypes were strain-specific.

OneHealth Approaches Contribute Towards Antimicrobial Resistance: Malaysian Perspective.

On a global scale, antimicrobial resistance (AMR) is recognized as a One Health challenge due to the continual and increased development and distribution of resistant microbes and genes among humans, animals, and the environment. These sectors contribute to the increase in AMR, as antibiotics are widely used in healthcare to treat or prevent bacterial infection; as growth enhancers, therapeutics and metaphylactics in animal husbandry; and transmitted in the environment through irrigation using wastewater or inappropriate disposal and treatment of human and agricultural waste. However, there is a major drawback in terms of the lack of research assessing the coexistence of AMR in these sectors. Extensive research highlighted food-animal manufacture structures that are likely to harbor reservoirs or promote transmission of AMR, in addition to increasing human colonization with AMR commensal bacteria. Numerous antibiotic stewardship policies have been designed and implemented in medical practices and animal husbandry in high- and middle-income countries. However, research concentrating on high-income settings, attitudes, emotions, and beliefs on the utilization of antimicrobials remain underexplored in lower- and middle-income countries such as Malaysia. Microbiological, epidemiological, and social science exploration are required at community and farming across the One Health range to fill huge gaps in information and knowledge of AMR. Manipulating human activities and character associated with antibiotics is a multifaceted progression that includes elements like knowledge, social behavior, attitudes, approaches, social standards, socioeconomic settings, peer pressure, experiences, and biophysical environment. Therefore, understanding these aspects in the utilization of antimicrobial drugs among the different sectors is essential to develop and implement policies to curb AMR development and transmission that overarch all sectors within the One Health consortium in Malaysia.

Hijacking of the Host's Immune Surveillance Radars by Burkholderia pseudomallei.

Burkholderia pseudomallei (B. pseudomallei) causes melioidosis, a potentially fatal disease for which no licensed vaccine is available thus far. The host-pathogen interactions in B. pseudomallei infection largely remain the tip of the iceberg. The pathological manifestations are protean ranging from acute to chronic involving one or more visceral organs leading to septic shock, especially in individuals with underlying conditions similar to COVID-19. Pathogenesis is attributed to the intracellular ability of the bacterium to 'step into' the host cell's cytoplasm from the endocytotic vacuole, where it appears to polymerize actin filaments to spread across cells in the closer vicinity. B. pseudomallei effectively evades the host's surveillance armory to remain latent for prolonged duration also causing relapses despite antimicrobial therapy. Therefore, eradication of intracellular B. pseudomallei is highly dependent on robust cellular immune responses. However, it remains ambiguous why certain individuals in endemic areas experience asymptomatic seroconversion, whereas others succumb to sepsis-associated sequelae. Here, we propose key insights on how the host's surveillance radars get commandeered by B. pseudomallei.

Cytotoxic Activity of Isoniazid Derivative in Human Breast Cancer Cells.

BACKGROUND/AIM: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells. MATERIALS AND METHODS: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays. RESULTS: ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G2/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death. CONCLUSION: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models.

Zerumbone mediates apoptosis and induces secretion of proinflammatory cytokines in breast carcinoma cell culture.

Objectives: To investigate the potential anti-breast cancer activity of zerumbone in regulating apoptotic mediators and cytokines in comparison with paclitaxel (positive control). Materials and Methods: In this study, assays such as viability, apoptosis, reactive oxygen species, cell cycle, DNA fragmentation, and cytokines were carried out on MCF-7 cells after treatment with zerumbone and paclitaxel. Results: The results showed that zerumbone demonstrated a higher (18-fold) IC50 value (126.7 µg/ml) than paclitaxel (7.29 µg/ml) in order to suppress proliferation and induce cell death of MCF-7. The cell cycle arrest at the G0/G1 phase and excessive intracellular ROS production during the in vitro zerumbone treatment indicated occurrence of apoptotic cell death although nuclear DNA fragmentation was not observed. The flow cytometer analysis of treated cells revealed secretion of proinflammatory cytokines suggesting the potential immunomodulatory activity of zerumbone. Conclusion: Although, zerumbone exhibited a higher IC50 value compared with paclitaxel yet its anticancer activity against MCF-7 cells is still parallel to paclitaxel hence zerumbone has the potential to be an antineoplastic agent in the treatment of breast cancer especially the luminal type A.