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In Malaysia, pneumonic pasteurellosis is one of the major problems in the small ruminant industry. Small ruminants especially goats are more susceptible to the disease that usually occurs due to stressful conditions. Cortisol plays an important role in the disease development of pneumonic pasteurellosis. The main objective of this study was to determine the correlation between cortisol concentration in vaccinated and non-vaccinated pneumonic goats. A total of 15 normal goats and 9 clinically infected pneumonic goats were selected from 2 vaccinated farms, whereas 15 normal goats and 31 clinically infected pneumonic goats from 2 non-vaccinated farms were selected for this study. Goats with clinical signs of nasal discharges, coughing with crackle lung sound were diagnosed as pneumonic goats. Blood samples were collected from the selected goats for cortisol evaluation. The study revealed that non-vaccinated clinically infected pneumonic goats exhibited a slightly higher (p>0.05) cortisol value compared to the other experimental goats. Therefore, it can be concluded that the use of plasma cortisol concentration as a measure of stress contributing towards pneumonic pasteurellosis in goats might not be the best way to confirm the influences of the disease. [ABSTRACT FROM AUTHOR]

Background: Dengue is a mosquito-borne disease caused by four distinct, closely related dengue viruses (DENV). Global dengue incidence has markedly increased in the past decades. The World Health Organization reported that cases increased from 505,430 in 2000 to 5.2 million in 2019. Similarly, the total dengue cases in Malaysia increased from 7,103 in 2000 to a peak of 130,101 in 2019. Knowledge, attitude, and practice (KAP) remain the most effective dengue prevention and control tools. Furthermore, school-based health education is key to enhancing knowledge and raising awareness of the seriousness of dengue among schoolchildren and transferring knowledge and practice from classrooms to homes. Thus, it is necessary to plan an integrated module for the primary prevention of dengue infection, specifically among schoolchildren., Aims: The present study intends to develop, implement, and evaluate the effectiveness of a theory-based integrated dengue education and learning (iDEAL) module in improving the KAP, environmental cleanliness index, and dengue index among schoolchildren in Selangor and Kuala Lumpur., Methods: This study is a single-blinded, cluster randomised controlled trial to be conducted from 1 September 2023 to 31 August 2025. The study will involve 20 primary and 20 secondary schools in Selangor and Kuala Lumpur. The 1600 participants will be randomly allocated to intervention and control groups based on selected clusters to avoid contamination. A cluster is a comparable school that fulfils the inclusion and exclusion criteria. The intervention group will receive the iDEAL module, while the control group will receive standard education. The iDEAL module will be developed following a systematic procedure and delivered in-person by trained researchers to the participants. The outcome will be measured using validated, self-administered questionnaires at baseline (T0), immediately (T1), one month (T2), and three months (T3) post-intervention to measure the intervention module effectiveness. The data will be analysed using IBM Statistical Package for Social Science (SPSS) version 28 and descriptive and inferential statistics. Within-group changes over time will be compared using one-way repeated measure analysis of variance for continuous and normally distributed variables. Within-group analysis of categorical data will use Cochran's Q test. The main effect and interaction between and within the intervention and control groups at T0, T1, T2, and T3 will be tested using the generalised linear mixed model (GLMM). Hypothetically, the KAP, environmental cleanliness index, and dengue index among the intervention group will be significantly improved compared to the control group. The hypothesis will be tested using a significance level with a p-value of 0.05 and a confidence interval of 95%., Conclusions: The study protocol outlines developing and testing an iDEAL module for schoolchildren in Selangor and Kuala Lumpur, with no socio-demographic differences expected. The intervention aims to improve KAP, environmental cleanliness index, and dengue index, potentially reducing dengue risk. Results could inform public health policies, emphasizing school-based interventions' importance in combating diseases like dengue., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Dapari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Breast cancer deaths disproportionately affect women living in low- and middle-income countries (LMICs). Patient navigation has emerged as a cost-effective and impactful approach to enable women with symptoms or suspicious mammogram findings to access timely diagnosis and patients with breast cancer to access timely and appropriate multimodality treatment. However, few studies have systematically evaluated the impact of patient navigation on timeliness of diagnosis and treatment in LMICs., Methods: We established a nurse- and community-navigator-led navigation program in breast clinics of four public hospitals located in Peninsular and East Malaysia and evaluated the impact of navigation on timeliness of diagnosis and treatment., Results: Patients with breast cancer treated at public hospitals reported facing barriers to accessing care, including having a poor recognition of breast cancer symptoms and low awareness of screening methods, and facing financial and logistics challenges. Compared with patients diagnosed in the previous year, patients receiving navigation experienced timely ultrasound (84.0% v 65.0%; P < .001), biopsy (84.0% v 78.0%; P = .012), communication of news (63.0% v 40.0%; P < .001), surgery (46% v 36%; P = .008), and neoadjuvant therapy (59% v 42%, P = .030). Treatment adherence improved significantly (98.0% v 87.0%, P < .001), and this was consistent across the network of four breast clinics., Conclusion: Patient navigation improves access to timely diagnosis and treatment for women presenting at secondary and tertiary hospitals in Malaysia.

Background: Improving help-seeking behaviour is a key component of down-staging breast cancer and improving survival, but the specific challenges faced by low-income women in an Asian setting remain poorly characterized. Here, we determined the extent of help-seeking delay among Malaysian breast cancer patients who presented at late stages and explored sub-groups of women who may face specific barriers., Methods: Time to help-seeking was assessed in 303 women diagnosed with advanced breast cancer between January 2015 and March 2020 at a suburban tertiary hospital in Malaysia. Two-step cluster analysis was conducted to identify subgroups of women who share similar characteristics and barriers. Barriers to help-seeking were identified from nurse interviews and were analyzed using behavioural frameworks., Results: The average time to help-seeking was 65 days (IQR = 250 days), and up to 44.5% of women delayed by at least 3 months. Three equal-sized clusters emerged with good separation by time to help-seeking (p < 0.001). The most reported barrier across clusters was poor knowledge about breast health or breast cancer symptoms (36.3%), regardless of help-seeking behaviour (p = 0.931). Unexpectedly, women with no delay (9 days average) and great delay (259 days average) were more similar to each other than to women with mild delays (58 days average), but, women who experienced great delay reported poor motivation due to fear and embarrassment (p = 0.066) and a lack of social support (p = 0.374) to seek help., Conclusions: Down-staging of breast cancer in Malaysia will require a multi-pronged approach aimed at modifying culturally specific social and emotional barriers, eliminating misinformation, and instilling motivation to seek help for breast health for the women most vulnerable to help-seeking delays., (© 2023. The Author(s).)

Development of resistance to chemo- and radiotherapy in patients suffering from advanced cervical cancer narrows the therapeutic window for conventional therapies. Previously we reported that a combination of the selective BCL-2 family inhibitors ABT-263 and A-1210477 decreased cell proliferation in C33A, SiHa and CaSki human cervical cancer cell lines. As ABT-263 binds to both BCL-2 and BCL-XL with high affinity, it was unclear whether the synergism of the drug combination was driven either by singly inhibiting BCL-2 or BCL-XL, or inhibition of both. In this present study, we used the BCL-2 selective inhibitor ABT-199 and the BCL-XL selective inhibitor A1331852 to resolve the individual antitumor activities of ABT-263 into BCL-2 and BCL-XL dependent mechanisms. A-1210477 was substituted for the orally bioavailable S63845. Four cervical cancer cell lines were treated with the selective BCL-2 family inhibitors ABT-199, A1331852 and S63845 alone and in combination using 2-dimensional (2D) and 3-dimensional (3D) cell culture models. The SiHa, C33A and CaSki cell lines were resistant to single agent treatment of all three drugs, suggesting that none of the BCL-2 family of proteins mediate survival of the cells in isolation. HeLa cells were resistant to single agent treatment of ABT-199 and A1331852 but were sensitive to S63845 indicating that they depend on MCL-1 for survival. Co-inhibition of BCL-2 and MCL-1 with ABT-199 and S63845, inhibited cell proliferation of all cancer cell lines, except SiHa. However, the effect of the combination was not as pronounced as combination of A1331852 and S63845. Co-inhibition of BCL-XL and MCL-1 with A1331852 and S63845 significantly inhibited cell proliferation of all four cell lines. Similar data were obtained with 3-dimensional spheroid cell culture models generated from two cervical cancer cell lines in vitro . Treatment with a combination of A1331852 and S63845 resulted in inhibition of growth and invasion of the 3D spheroids. Collectively, our data demonstrate that the combination of MCL-1-selective inhibitors with either selective inhibitors of either BCL-XL or BCL-2 may be potentially useful as treatment strategies for the management of cervical cancer., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Authors.)

Main Conclusion: The rice leaf mitochondrial DNA is  more methylated compared to the rice grain mitochondrial DNA. The old rice leaf mitochondrial DNA has also a higher methylation level than the young rice leaf mitochondrial DNA. The presence of DNA methylation in rice organelles has not been well characterized. We have previously shown that cytosine methylation of chloroplast DNA is different between leaf and grain, and varies between young and old leaves in rice. However, the variation in cytosine methylation of mitochondrial DNA is still poorly characterized. In this study, we have investigated cytosine methylation of mitochondrial DNA in the rice grain and leaf. Based on CpG, CHG, and CHH methylation analyses, the leaf mitochondrial DNA was found to be  more methylated compared to the grain mitochondrial DNA. The methylation of the leaf mitochondrial DNA was also higher in old compared to young leaves. Differences in methylation were observed at different cytosine positions of the mitochondrial DNA between grain and leaf, although there were also positions with a similar level of high methylation in all the tissues examined. The differentially methylated cytosine positions in rice mitochondrial DNA were observed mostly in the intergenic region and in some mitochondrial-specific genes involved in ATP production, transcription, and translation. The functional importance of cytosine methylation in the life cycle of rice mitochondria is still to be determined.

Key Message: Grain amyloplast and leaf chloroplast DNA sequences are identical in rice plants but are differentially methylated. The leaf chloroplast DNA becomes more methylated as the rice plant ages. Rice is an important crop worldwide. Chloroplasts and amyloplasts are critical organelles but the amyloplast genome is poorly studied. We have characterised the sequence and methylation of grain amyloplast DNA and leaf chloroplast DNA in rice. We have also analysed the changes in methylation patterns in the chloroplast DNA as the rice plant ages. Total genomic DNA from grain, old leaf and young leaf tissues were extracted from the Oryza sativa ssp. indica cv. MR219 and sequenced using Illumina Miseq. Sequence variant analysis revealed that the amyloplast and chloroplast DNA of MR219 were identical to each other. However, comparison of CpG and CHG methylation between the identical amyloplast and chloroplast DNA sequences indicated that the chloroplast DNA from rice leaves collected at early ripening stage was more methylated than the amyloplast DNA from the grains of the same plant. The chloroplast DNA became more methylated as the plant ages so that chloroplast DNA from young leaves was less methylated overall than amyloplast DNA. These differential methylation patterns were primarily observed in organelle-encoded genes related to photosynthesis followed by those involved in transcription and translation.

Wound healing is a natural intricate cascade process involving cellular, biochemical and molecular mechanism to restore the injured or wounded tissue. Malaysia's multi-ethnic social fabric is reflected in its different traditional folk cuisines with different nutritional important ingredients. Despite these differences, there are some commonly used pantry ingredients among Malaysians and these ingredients may possess some healing power for acute and chronic wounds. These essential nutritional ingredients are included Amla (Ribes uva-crispa), Cinnamon (Cinnamomun venum), Curry Leaves (Murraya koenigii), Coriander (Coriandrum sativum), Fenugreek (Trigonella foenum-graecum), Garlic (Allium indica), Onion (Allium cepa) and Tamarind (Tamarindus indica). This article provides a review of the remedies with confirmed wound healing activities from previous experiments conducted by various researchers. Most of the researchers have focused only on the preliminary studies through appropriate model; hence detailed investigations which including pharmacological and pre-clinical studies are needed to discover its molecular mechanisms. In this review article, we have discussed about the wound healing potential of few commonly used edible plants and their known mechanism.

Colorectal cancer (CRC) is ranked as the fourth most lethal and commonly diagnosed cancer in the world according to the National Cancer Institute's latest report. Treatment methods for CRC are constantly being studied for advancement, which leads for more clinically effective cancer curing strategy. Patients with prolonged chronic inflammation caused by ulcerative colitis or similar inflammatory bowel disease are known to have high risks of developing CRC. But at a molecular level, oxidative stress due to reactive oxygen species (ROS) is an important trigger for cancer. Hence, in recent years, exogenous antioxidants have been immensely experimented in pre-clinical and clinical trials, considering it as a potential cure for CRC. Significantly, potential antioxidant compounds especially derivatives of medicinal plants have received great attention in the current research trend for CRC treatment. Though antioxidant compounds seem to have beneficial properties for the treatment of CRC, there are also limitations for pure compounds to be tested clinically. Therefore, this review aims to delineate the pharmacological awareness among researchers on using antioxidant compounds to treat CRC and the measures taken to prove the effectiveness of such compounds as impending drug candidates for CRC treatment in modern medication., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Alternanthera sessilis , an edible succulent herb, has been widely used as herbal drug in many regions around the globe. Inflammation is a natural process of the innate immune system, accompanied with the increase in the level of proinflammatory mediators, for example, nitric oxide (NO) and prostaglandin (PGE 2 ); cytokines such as interleukin 6 (IL-6), interleukin 1 β (IL-1 β ), and tumor necrosis factor alpha (TNF α ); and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via the activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κ B) subunit p65 due to the phosphorylation of inhibitory protein, I κ B α . Inflammation over a short period of time is essential for its therapeutic effect. However, prolonged inflammation can be detrimental as it is related to many chronic diseases such as delayed wound healing, cardiovascular disease, arthritis, and autoimmune disorders. Therefore, ways to curb chronic inflammation have been extensively investigated. In line with that, in this present study, we attempted to study the suppression activity of the proinflammatory cytokines and mediators as a characteristic of anti-inflammatory action, by using stem extract of A. sessilis in the lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The results showed that the extract has significantly inhibited the production of the proinflammatory mediators including NO and PGE 2 ; cytokines comprising IL-6, IL-1 β , and TNF α ; and enzymes covering the iNOS and COX-2 by preventing the I κ B α from being degraded, to inhibit the nuclear translocation of NF- κ B subunit p65 in order to hinder the inflammatory pathway activation. These results indicated that the stem extract of A. sessilis could be an effective candidate for ameliorating inflammatory-associated complications.

Objective: There are number of studies which report that BCL-2 anti-apoptotic proteins (e.g. BCL-2, BCL-XL, and MCL-1) are highly expressed in cervical cancer tissues compared to the normal cervical epithelia. Despite these reports, targeting these proteins for cervical cancer treatment has not been explored extensively. BH3-mimetics that inhibit specific BCL-2 anti-apoptotic proteins may hold encouraging treatment outcomes for cervical cancer management. Hence, the aim of this pilot study is to investigate the sensitivity of cervical cancer cell lines to combination of two BH3-mimetics namely ABT-263 which selectively inhibits BCL-2, BCL-XL and BCL-w and A-1210477, a selective MCL-1 inhibitor., Results: We report that combination of A-1210477 and ABT-263 exhibited synergistic effects on all cervical cancer cell lines tested. Drug sensitization studies revealed that A-1210477 sensitised the cervical cancer cell lines SiHa and CaSki to ABT-263 by 11- and fivefold, respectively. Sensitization also occurred in the opposite direction whereby ABT-263 sensitised SiHa and CaSki to A-1210477 by eightfold. This report shows that combination of ABT-263 and A-1210477 could be a potential treatment strategy for cervical cancer. Extensive drug mechanistic studies and drug sensitivity studies in physiological models are necessary to unleash the prospect of this combination for cervical cancer therapy.

Impaired wound healing is one of the serious problems among the diabetic patients. Currently, available treatments are limited due to side effects and cost effectiveness. In line with that, we attempted to use a natural source to study its potential towards the wound healing process. Therefore, Alternanthera sessilis ( A. sessilis ), an edible and medicinal plant, was chosen as the target sample for the study. During this investigation, the wound closure properties using stem extract of A. sessilis were analyzed. Accordingly, we analyzed the extract on free radical scavenging capacity and the cell migration of two most prominent cell types on the skin, human dermal fibroblast (NHDF), keratinocytes (HaCaT), and diabetic human dermal fibroblast (HDF-D) to mimic the wound healing in diabetic patients. The bioactive compounds were identified using gas chromatography-mass spectrometry (GC-MS). We discovered that the analysis exhibited a remarkable antioxidant, proliferative, and migratory rate in NHDF, HaCaT, and HDF-D in dose-dependent manner, which supports wound healing process, due to the presence of wound healing associated phytocompounds such as Hexadecanoic acid. This study suggested that the stem extract of A. sessilis might be a potential therapeutic agent for skin wound healing, supporting its traditional medicinal uses.

Background: Moringa oleifera (MO), commonly known as the drumstick tree, is used in folklore medicine for the treatment of skin disease., Objective: The objective of this study is to evaluate the ethyl acetate (EtOAc) fraction of MO leaves for in vitro antibacterial, antioxidant, and wound healing activities and conduct gas chromatography-mass spectrometry (GC-MS) analysis., Materials and Methods: Antibacterial activity was evaluated against six Gram-positive bacteria and 10 Gram-negative bacteria by disc diffusion method. Free radical scavenging activity was assessed by 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical hydrogen peroxide scavenging and total phenolic content (TPC). Wound healing efficiency was studied using cell viability, proliferation, and scratch assays in diabetic human dermal fibroblast (HDF-D) cells., Results: The EtOAc fraction showed moderate activity against all bacterial strains tested, and the maximum inhibition zone was observed against Streptococcus pyogenes (30 mm in diameter). The fraction showed higher sensitivity to Gram-positive strains than Gram-negative strains. In the quantitative analysis of antioxidant content, the EtOAc fraction was found to have a TPC of 65.81 ± 0.01. The DPPH scavenging activity and the hydrogen peroxide assay were correlated with the TPC value, with IC 50 values of 18.21 ± 0.06 and 59.22 ± 0.04, respectively. The wound healing experiment revealed a significant enhancement of cell proliferation and migration of HDF-D cells. GC-MS analysis confirmed the presence of 17 bioactive constituents that may be the principal factors in the significant antibacterial, antioxidant, and wound healing activity., Conclusion: The EtOAc fraction of MO leaves possesses remarkable wound healing properties, which can be attributed to the antibacterial and antioxidant activities of the fraction., Summary: Moringa oleifera (MO) leaf ethyl acetate (EtOAc) fraction possesses antibacterial activities toward Gram-positive bacteria such as Streptococcus pyogenes , Streptococcus faecalis , Bacillus subtilis , Bacillus cereus and Staphylococcus aureus , and Gram-negative bacteria such as Proteus mirabilis and Salmonella typhimurium MO leaf EtOAc fraction contained the phenolic content of 65.81 ± 0.01 and flavonoid content of 37.1 ± 0.03, respectively. In addition, the fraction contained 17 bioactive constituents associated with the antibacterial, antioxidant, and wound healing properties that were identified using gas chromatography-mass spectrometry analysisMO leaf EtOAc fraction supports wound closure rate about 80% for treatments when compared with control group. Abbreviations used: MO: Moringa oleifera ; EtOAc: Ethyl acetate; GC-MS: Gas Chromatography-Mass Spectrometry; HDF-D: Diabetic Human Dermal Fibroblast cells., Competing Interests: There are no conflicts of interest.

Nasopharyngeal carcinoma (NPC) is a type of cancer endemic in Asia, including Malaysia, Southern China, Hong Kong and Taiwan. Treatment resistance, particularly in recurring cases, remains a challenge. Thus, studies to develop novel therapeutic agents are important. Potential therapeutic compounds may be effectively examined using two-dimensional (2D) cell culture models, three-dimensional (3D) spheroid models or in vivo animal models. The majority of drug assessments for cancers, including for NPC, are currently performed with 2D cell culture models. This model offers economical and high-throughput screening advantages. However, 2D cell culture models cannot recapitulate the architecture and the microenvironment of a tumor. In vivo models may recapitulate certain architectural and microenvironmental conditions of a tumor, however, these are not feasible for the screening of large numbers of compounds. By contrast, 3D spheroid models may be able to recapitulate a physiological microenvironment not observed in 2D cell culture models, in addition to avoiding the impediments of in vivo animal models. Thus, the 3D spheroid model offers a more representative model for the study of NPC growth, invasion and drug response, which may be cost-effective without forgoing quality.

Spheroids have been shown to recapitulate the tumour in vivo with properties such as the tumour microenvironment, concentration gradients, and tumour phenotype. As such, it can serve as a platform for determining the growth and invasion behaviour pattern of the cancer cells as well as be utilised for drug sensitivity assays; capable of exhibiting results that are closer to what is observed in vivo compared to two-dimensional (2D) cell culture assays. This study focused on establishing a three-dimensional (3D) cell culture model using the Nasopharyngeal Carcinoma (NPC) cell line, HK1 and analysing its growth and invasion phenotypes. The spheroids will also serve as a model to elucidate their sensitivity to the chemotherapeutic drug, Flavopiridol. The liquid overlay method was employed to generate the spheroids which was embedded in bovine collagen I matrix for growth and invasion phenotypes observation. The HK1 cells formed compact spheroids within 72 hours. Our observation from the 3 days experiments revealed that the spheroids gradually grew and invaded into the collagen matrix, showing that the HK1 spheroids are capable of growth and invasion. Progressing from these experiments, the HK1 spheroids were employed to perform a drug sensitivity assay using the chemotherapeutic drug, Flavopiridol. The drug had a dose-dependent inhibition on spheroid growth and invasion.

In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions were not cytotoxic to macrophages at concentrations up to 200 µg/mL. The ethyl acetate fraction suppressed LPS-induced production of nitric oxide and proinflammatory cytokines in macrophages in a concentration-dependent manner and was more effective than the other fractions. Immunoblot observations revealed that the ethyl acetate fraction effectively inhibited the expression of inflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor (NF)-κB p65 through suppression of the NF-κB signaling pathway. Furthermore, it upregulated the expression of the inhibitor of κB (IκBα) and blocked the nuclear translocation of NF-κB. These findings indicated that the ethyl acetate fraction of M. oleifera exhibited potent anti-inflammatory activity in LPS-stimulated macrophages via suppression of the NF-κB signaling pathway.