Predictors of musculoskeletal disorders among special education teachers in Sabah, Malaysia.

Special education teachers encounter considerable occupational challenges, yet there is limited information concerning musculoskeletal disorders (MSD) within this group. Therefore, this study aimed to address this gap by determining the prevalence of MSD, investigating associated factors of MSD, and identifying predictors of MSD among special education teachers. A cross-sectional study was conducted among special education teachers in Kota Kinabalu and Penampang, Sabah. Data were collected through self-administered questionnaires and musculoskeletal fitness assessments. Chi-square tests and independent t-tests were utilized to determine factors associated with MSD, while multiple logistic regression was performed to develop a comprehensive predictive model for MSD, which was then validated and tested for model fitness. A total of 122 individuals participated in the study, yielding a response rate of 95 %. The findings revealed a high prevalence of MSD (77.9 %) among special education teachers, with the lower back, shoulder, neck, knee, upper back, and foot being the most affected regions. The multivariable regression model identified several predictors of MSD, including marital status (adjusted odds ratio [aOR] = 4.78, 95 % confidence interval [CI] = 1.49-15.40), body fat percentage (aOR = 1.06, 95 % CI = 1.00-1.12), teaching in prolonged standing for few days a week (aOR = 3.20, 95 % CI = 0.99-10.29) or every day (aOR = 6.20, 95 % CI = 1.44-26.70), mindfulness (aOR = 0.47, 95 % CI = 0.22-0.98), and back extensor strength (aOR = 5.86, 95 % CI = 1.92-17.92). This study highlights the necessity of implementing interventions focusing on the ergonomic, psychological, and musculoskeletal fitness components to mitigate the prevalence of MSD and improve the overall well-being of special education teachers.

The Pleiotropic Role of Extracellular ATP in Myocardial Remodelling.

Myocardial remodelling is a molecular, cellular, and interstitial adaptation of the heart in response to altered environmental demands. The heart undergoes reversible physiological remodelling in response to changes in mechanical loading or irreversible pathological remodelling induced by neurohumoral factors and chronic stress, leading to heart failure. Adenosine triphosphate (ATP) is one of the potent mediators in cardiovascular signalling that act on the ligand-gated (P2X) and G-protein-coupled (P2Y) purinoceptors via the autocrine or paracrine manners. These activations mediate numerous intracellular communications by modulating the production of other messengers, including calcium, growth factors, cytokines, and nitric oxide. ATP is known to play a pleiotropic role in cardiovascular pathophysiology, making it a reliable biomarker for cardiac protection. This review outlines the sources of ATP released under physiological and pathological stress and its cell-specific mechanism of action. We further highlight a series of cardiovascular cell-to-cell communications of extracellular ATP signalling cascades in cardiac remodelling, which can be seen in hypertension, ischemia/reperfusion injury, fibrosis, hypertrophy, and atrophy. Finally, we summarize current pharmacological intervention using the ATP network as a target for cardiac protection. A better understanding of ATP communication in myocardial remodelling could be worthwhile for future drug development and repurposing and the management of cardiovascular diseases.

A Case Report on Core Muscles Training for Knee Osteoarthritis Through Core Muscles Activations and Gait Analysis.

Knee osteoarthritis (OA) is a chronic joint disease that can affect all ages, but it is more common in the elderly. Pharmacological and non-pharmacological treatments have been invented evolutionarily over the years to halt this disease. Exercise is one of the first-line treatments for knee OA as well as for prevention. This case study features a 47-year-old man who has grade IV bilateral knee OA and has never had any surgery and takes fish oil daily as a supplement. His walking pattern was significantly impacted by the chronic knee discomfort he had in both legs. Thus, the walking gait of this patient was analyzed together with core muscle activation before and after two weeks of core resistance exercise intervention. The knee pain score was assessed using the Western Ontario and McMaster Universities Index (WOMAC). The outcomes of this research depict that core resistance training has the potential to be used as an alternative, non-surgical and non-pharmacological treatment for a patient with knee OA.

Modulation of POPDC1 Expression by Phenothiazine and Trifluoperazine Suppress Colon Cancer Growth and Migration.

OBJECTIVE: The aim of this study was to investigate the effects of CaM antagonist, PTZ, and TFP on cell proliferation and migration of colon cancer cells and its impact on POPDC protein expression. METHODS: The 50% inhibitory concentration (IC50) of PTZ and TFP in SW1116, SW480, HCT-15, and COLO205 colon cancer cell lines are measured using MTT. Western blot and immunocytochemistry were used to determine the expression of PCNA, cyclin D1 (CD1), and POPDC proteins. Cell migration was observed using a scratch wound-healing assay. RESULTS: Treatment with PTZ and TFP inhibited colon cancer cells growth in a dose-dependent manner. PTZ and TFP significantly inhibited the activation of proliferation markers, PCNA and CD1, and the migration of colon cancer cells. Furthermore, POPDC protein was significantly suppressed in all cell types of colon cancer, particularly in SW480. Finally, the CaM antagonist upregulates the POPDC1 expression in colon cancer cells. CONCLUSION: These findings suggest that CaM antagonists suppress colon cancer cells proliferation via downregulation of CD1 and PCNA. In addition, POPDC protein could be used as a biomarker in colon cancer, and CaM antagonist could be used to regulate POPDC1 expression. This study suggests that targeting POPDC1 with CaM inhibition could be a potential therapeutic strategy for colon cancer treatment. 
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Carpaine Promotes Proliferation and Repair of H9c2 Cardiomyocytes after Oxidative Insults.

Carpaine has long been identified as the major alkaloid in Carica papaya leaves that possess muscle relaxant properties. Limited study on the molecular signaling properties of carpaine urges us to conduct this study that aims to elucidate the mechanism underlying the cardioprotective effect of carpaine in embryonic cardiomyocytes of the H9c2 cell line. The 50% inhibitory concentration (IC50) of carpaine was first determined using a colorimetric MTT assay to establish the minimum inhibitory concentration for the subsequent test. Using a 1 µM carpaine treatment, a significant increase in the H9c2 proliferation rate was observed following 24 and 48 h of incubation. A Western blot analysis also revealed that carpaine promotes the upregulation of the cell cycle marker proteins cyclin D1 and PCNA. Carpaine-induced H9c2 cell proliferation is mediated by the activation of the FAK-ERK1/2 and FAK-AKT signaling pathways. In the setting of ischemia-reperfusion injury (IRI), carpaine provided a significant protective role to recover the wounded area affected by the hydrogen peroxide (H2O2) treatment. Furthermore, the oxidative-stress-induced reduction in mitochondrial membrane potential (MMP) and overproduction of reactive oxygen species (ROS) were attenuated by carpaine treatment. The current study revealed a novel therapeutic potential of carpaine in promoting in vitro cardiomyocyte proliferation and repair following injury.

Genotype-Phenotype Study of ß-Thalassemia Patients in Sabah.

ß-thalassemia is a serious public health problem in Sabah due to its high prevalence. This study aimed to investigate the effects of different types of ß-globin gene mutations, coinheritance with α-globin gene mutations, XmnI-Gγ, and rs368698783 polymorphisms on the ß-thalassemia phenotypes in Sabahan patients. A total of 111 patients were included in this study. The sociodemographic profile of the patients was collected using a semi-structured questionnaire, while clinical data were obtained from their medical records. Gap-PCR, ARMS-PCR, RFLP-PCR, and multiplex PCR were performed to detect ß- and α-globin gene mutations, as well as XmnI-Gγ and rs368698783 polymorphisms. Our data show that the high prevalence of ß-thalassemia in Sabah is not due to consanguineous marriages (5.4%). A total of six different ß-globin gene mutations were detected, with Filipino ß°-deletion being the most dominant (87.4%). There were 77.5% homozygous ß-thalassemia patients, 16.2% compound heterozygous ß-thalassemia patients, and 6.3% ß-thalassemia/Hb E patients. Further evaluation on compound heterozygous ß-thalassemia and ß-thalassemia/Hb E patients found no concomitant α-globin gene mutations and the rs368698783 polymorphism. Furthermore, the XmnI-Gγ (-/+) genotype did not demonstrate a strong impact on the disease phenotype, as only two of five patients in the compound heterozygous ß-thalassemia group and two of three patients in the ß-thalassemia/Hb E group had a moderate phenotype. Our findings indicate that the severity of the ß-thalassemia phenotypes is closely related to the type of ß-globin gene mutations but not to the XmnI-Gγ and rs368698783 polymorphisms.

Dual Anti-Malarial and GSK3ß-Mediated Cytokine-Modulating Activities of Quercetin Are Requisite of Its Potential as a Plant-Derived Therapeutic in Malaria.

Although death in malaria is attributed to cerebrovascular blockage and anaemia, overwhelming cytokine production can contribute to the severity of the disease. Therefore, mitigation of dysregulated inflammatory signalling may provide further benefit for malaria treatment. Quercetin (3,3',4',5,7-pentahydroxyflavone) is known to inhibit glycogen synthase kinase-3ß (GSK3ß), a potent regulator of both pro- and anti-inflammatory effects. Quercetin is therefore a potential therapeutic to modulate the imbalanced cytokine production during malarial infection. Anti-malarial effects of quercetin were evaluated in murine models of severe and cerebral malaria using Plasmodium berghei NK65 and ANKA strains, respectively. Western blotting and analysis of cytokines were carried out to determine the GSK3ß-mediated cytokine-modulating effects of quercetin in infected animals. Quercetin (25 mg/kg BW) treatment in P. berghei NK65-infected animals resulted in 60.7 ± 2.4% suppression of parasitaemia and significantly decreased serum levels of TNF-α and IFN-γ, whilst levels of IL-10 and IL-4 were elevated significantly. Western analysis revealed that pGSK3ß (Ser9) increased 2.7-fold in the liver of quercetin-treated NK65-infected animals. Treatment of P. berghei ANKA-infected mice with quercetin (15 mg/kg BW) increased (2.3-fold) pGSK3ß (Ser9) in the brains of infected animals. Quercetin is a potential plant-derived therapeutic for malaria on the basis that it can elicit anti-malarial and GSK3ß-mediated cytokine-modulating effects.

TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy.

Myocardial atrophy, characterized by the decreases in size and contractility of cardiomyocytes, is caused by severe malnutrition and/or mechanical unloading. Extracellular adenosine 5'-triphosphate (ATP), known as a danger signal, is recognized to negatively regulate cell volume. However, it is obscure whether extracellular ATP contributes to cardiomyocyte atrophy. Here, we report that ATP induces atrophy of neonatal rat cardiomyocytes (NRCMs) without cell death through P2Y2 receptors. ATP led to overproduction of reactive oxygen species (ROS) through increased amount of NADPH oxidase (Nox) 2 proteins, due to increased physical interaction between Nox2 and canonical transient receptor potential 3 (TRPC3). This ATP-mediated formation of TRPC3-Nox2 complex was also pathophysiologically involved in nutritional deficiency-induced NRCM atrophy. Strikingly, knockdown of either TRPC3 or Nox2 suppressed nutritional deficiency-induced ATP release, as well as ROS production and NRCM atrophy. Taken together, we propose that TRPC3-Nox2 axis, activated by extracellular ATP, is the key component that mediates nutritional deficiency-induced cardiomyocyte atrophy.

The Antimalarial Effect of Curcumin Is Mediated by the Inhibition of Glycogen Synthase Kinase-3ß.

Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3ß (GSK3ß)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3ß. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3ß and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3ß.