Prevention of aspirin-mediated secondary toxicity by combined treatment of carotenoids in macrophages.

Upon understanding the boosting role of carotenoids on the endogenous anti-inflammatory system, it is vital to explore their role in reducing the use of high doses of non-steroidal anti-inflammatory drug (NSAIDs), and their mediated secondary toxicity during the treatment of chronic diseases. The current study investigates the carotenoids potential on inhibition of secondary complications induced by NSAIDs, aspirin (ASA) against lipopolysaccharide (LPS) stimulated inflammation. Initially, this study evaluated a minimal cytotoxic dose of ASA and carotenoids (ß-carotene, BC/lutein, LUT/astaxanthin, AST/fucoxanthin FUCO) in Raw 264.7, U937, and peripheral blood mononuclear cells (PBMCs). In all three cells, carotenoids + ASA treatment reduced the LDH release, NO, and PGE2 efficiently than an equivalent dose of carotenoid or ASA treated alone. Based on cytotoxicity and sensitivity results, RAW 264.7 cells were selected for further cell-based assay. Among carotenoids, FUCO + ASA exhibited an efficient reduction of LDH release, NO, and PGE2 than the other carotenoids (BC + ASA, LUT + ASA, and AST + ASA) treatment. FUCO + ASA combination decreased LPS/ASA induced oxidative stress, pro-inflammatory mediators (iNOS, COX-2, and NF-κB), and cytokines (IL-6, TNF-α, and IL-1ß) efficiently. Further, apoptosis was inhibited by 69.2% in FUCO + ASA, and 46.7% in ASA than LPS treated cells. A drastic decrease in intracellular ROS generation with the increase in GSH was observed in FUCO + ASA compared to LPS/ASA groups. The results documented on the low dose of ASA with a relative physiological concentration of FUCO suggested greater importance for alleviating secondary complications and optimize prolonged chronic disease treatments with NSAID's associated side effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03632-w.

Diagnostic accuracy of the tongue blade test combined with clinical signs to detect maxillary and mandibular fractures in the emergency department.

BACKGROUND: To evaluate the diagnostic accuracy of clinical signs combined with the tongue blade test (TBT) to detect maxillary and mandibular fractures. METHODS: A cross-sectional study enrolled patients with maxillary and mandibular injuries in the emergency department. Physical examination and the TBT were performed, followed by radiological imaging (facial X-ray or computed tomography [CT]). The diagnostic accuracy was calculated for individuals and a combination of clinical findings at predicting maxillary and mandibular fractures. RESULTS: A total of 98 patients were identified, of whom 31.6% had maxillary fractures and 9.2% had mandibular fractures. The combination of malocclusion, tenderness on palpation and swelling with positive TBT had 100% specificity to detect maxillary and mandibular fractures. In the absence of malocclusion, the combination of tenderness on palpation and swelling with positive TBT produced a specificity of 97.8% for maxillary fracture and a specificity of 96.2% for mandibular fracture. A clinical decision tool consisting of malocclusion, tenderness on palpation, swelling and TBT revealed a specificity of 100% and a positive predictive value of 100%. CONCLUSION: The clinical decision tool is potentially useful to rule out mandibular fractures, thus preventing unnecessary radiation exposure.

Can metagenomics unravel the impact of oral bacteriome in human diseases?

Oral microbial ecosystems are vital in maintaining the health of the oral cavity and the entire body. Oral microbiota is associated with the progression of oral diseases such as dental caries, periodontal diseases, head and neck cancer, and several systemic diseases such as cardiovascular disease, rheumatoid arthritis, adverse pregnancy outcomes, diabetes, lung infection, colorectal cancer, and pancreatic cancer. Buccal mucosa, tongue dorsum, hard palate, saliva, palatine tonsils, throat, keratinized gingiva, supra-gingival plaque, subgingival plaque, dentures, and lips are microbial habitats of the oral cavity. Porphyromonas gingivalis may have a role in the development of periodontal diseases, oral cancer, diabetes, and atherosclerotic disease. Fusobacterium nucleatum showed a higher abundance in periodontal diseases, oral and colon cancer, adverse pregnancy outcomes, diabetes, and rheumatoid arthritis. The higher abundance of Prevotella intermedia is typical in periodontal diseases, rheumatoid arthritis, and adverse pregnancy outcome. S. salivarius displayed higher abundance in both dental caries and OSCC. Oral bacteria may influence systemic diseases through inflammation by releasing pro inflammatory cytokines. Identification of oral bacteria using culture-dependent approaches and next-generation sequencing-based metagenomic approaches is believed to significantly identify the therapeutic targets and non-invasive diagnostic indicators in different human diseases. Oral bacteria in saliva could be exploited as a non-invasive diagnostic indicator for the early detection of oral and systemic disorders. Other therapeutic approaches such as the use of probiotics, green tea polyphenol, cold atmospheric plasma (CAP) therapy, antimicrobial photodynamic therapy, and antimicrobial peptides are used to inhibit the growth of biofilm formation by oral bacteria.

Porphyromonas gingivalis may have a role in the development of periodontal diseases, oral cancer, diabetes, and atherosclerotic diseaseFusobacterium nucleatum showed a higher abundance in periodontal diseases, oral and colon cancer, adverse pregnancy outcomes, diabetes, and rheumatoid arthritisOral bacteria may influence systemic diseases through inflammation by releasing pro inflammatory cytokines.Identification of oral bacteria in saliva may be used as a non-invasive diagnostic indicator for the early detection of oral and systemic disorders.

Host immune response against DENV and ZIKV infections.

Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses.

Revisiting Mitochondria Scored Cancer Progression and Metastasis.

The Warburg effect has immensely succored the study of cancer biology, especially in highlighting the role of mitochondria in cancer stemness and their benefaction to the malignancy of oxidative and glycolytic cancer cells. Mitochondrial genetics have represented a focal point in cancer therapeutics due to the involvement of mitochondria in programmed cell death. The mitochondrion has been well established as a switch in cell death decisions. The mitochondrion's instrumental role in central bioenergetics, calcium homeostasis, and translational regulation has earned it its fame in metastatic dissemination in cancer cells. Here, we revisit and review mechanisms through which mitochondria influence oncogenesis and metastasis by underscoring the oncogenic mitochondrion that is capable of transferring malignant capacities to recipient cells.

Correlation of host inflammatory cytokines and immune-related metabolites, but not viral NS1 protein, with disease severity of dengue virus infection.

Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.

Knowledge of and willingness to perform Hands-Only cardiopulmonary resuscitation among college students in Malaysia.

Worldwide, millions of people die of sudden cardiac arrest every year. This is partly due to limited and sometimes ineffective bystander cardiopulmonary resuscitation (CPR). The need for mouth-to-mouth contact, fear of causing harm, litigation, and the complexity of delivering CPR are the main deterrents. In view of this, the basic life support algorithm has been simplified and lay rescuers are encouraged to perform Hands-Only CPR.The objective of this study is to assess knowledge on and willingness to perform Hands-Only CPR among Malaysian college students and to determine the relationship between the two.In an online self-administered survey, college students responded to a questionnaire on demographics, exposure to CPR, knowledge on Hands-Only CPR, and their willingness to perform Hands-Only CPR in 5 different scenarios (family members or relatives, strangers, trauma victims, children, and elderly people).Data for 393 participants were analyzed. For knowledge, the mean score was 8.6 ±â€Š3.2 and the median score was 9. In the sample, 27% of the respondents did not attend any CPR training before, citing that they were unsure where to attend the course. The knowledge score among those who attended CPR training (M = 3.6, S = 2.9) was significantly higher compared to those who did not (M = 6.7, S = 3.0). Out of the 393 participants, 67.7%, 55%, 37.4%, 45%, and 49.1% were willing to perform Hands-Only CPR on family members or relatives, strangers, trauma victims, children, and elderly people, respectively. There were significant associations (P < .001) between knowledge and willing to perform Hands-Only CPR on family members or relatives (OR = 1.32, 95% CI 1.43, 1.43), strangers (OR = 1.31, 95% CI 1.21, 1.42), trauma victims (OR = 1.21, 95% CI 1.12, 1.31), children (OR = 1.28, 95% CI 1.19, 1.39), and elderly people (OR = 1.36 95% CI 1.25, 1.48).Based on this study, knowledge on Hands-Only CPR among local college students is not encouraging. Not many know where to attend such courses. There was significant association between knowledge and willingness to perform Hands-Only CPR.

Factors Associated with Health Care Professionals' Attitude Toward the Presumed Consent System.

OBJECTIVES: This paper explores health care professionals' potential attitude toward organ donation if the presumed consent system were to be implemented in Malaysia, as well as factors associated with this attitude. MATERIALS AND METHODS: We used self-administered questionnaires to investigate the attitude of 382 health care professionals from the University of Malaya Medical Center between January and February 2014. The responses were analyzed using logistic regression. RESULTS: Of the 382 respondents, 175 (45.8%) stated that they would officially object to organ donation if the presumed consent system were to be implemented, whereas the remaining 207 (54.2%) stated that they would not object. The logistic regression showed that health care professionals from the Malay ethnic group were more likely to object than those from Chinese (adjusted odds ratio of 0.342; P = .001) and Indian and other (adjusted odds ratio of 0.341; P = .003) ethnic groups. Health care professionals earning 3000 Malaysian Ringgit or below were more likely to object than those earning above 3000 Malaysian Ringgit (adjusted odds ratio of 1.919; P = .006). Moreover, respondents who were initially unwilling to donate organs, regardless of the donation system, were more likely to object under the presumed consent system than those who were initially willing to donate (adjusted odds ratio of 2.765; P < .001). CONCLUSIONS: Health care professionals in Malaysia have a relatively negative attitude toward the presumed consent system, which does not encourage the implementation of this system in the country at present. To pave the way for a successful implementation of the presumed consent system, efforts should be initiated to enhance the attitude of health care professionals toward this system. In particular, these efforts should at most target the health care professionals who are Malay, earn a low income, and have a negative default attitude toward deceased donation.

Loss of Transfected Human Brain Micro-Vascular Endothelial Cell Integrity during Herpes Simplex Virus Infection.

OBJECTIVE: Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier. METHOD: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection. RESULTS: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells. CONCLUSION: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.

Comparative genomic analysis of ten clinical Streptococcus pneumoniae collected from a Malaysian hospital reveal 31 new unique drug-resistant SNPs using whole genome sequencing.

BACKGROUND: Streptococcus pneumoniae or pneumococcus is a leading cause of morbidity and mortality worldwide, specifically in relation to community-acquired pneumonia. Due to the overuse of antibiotics, S. pneumoniae has developed a high degree of resistance to a wide range of antibacterial drugs. METHODS: In this study, whole genome sequencing (WGS) was performed for 10 clinical strains of S. pneumoniae with different levels of sensitivity to standard antibiotics. The main objective was to investigate genetic changes associated with antibiotic resistance in S. pneumoniae. RESULTS: Our results showed that resistant isolates contain a higher number of non-synonymous single nucleotide polymorphisms (SNPs) as compared to susceptible isolates. We were able to identify SNPs that alter a single amino acid in many genes involved in virulence and capsular polysaccharide synthesis. In addition, 90 SNPs were only presented in the resistant isolates, and 31 SNPs were unique and had not been previously reported, suggesting that these unique SNPs could play a key role in altering the level of resistance to different antibiotics. CONCLUSION: Whole genome sequencing is a powerful tool for comparing the full genome of multiple isolates, especially those closely related, and for analysing the variations found within antibiotic resistance genes that lead to differences in antibiotic sensitivity. We were able to identify specific mutations within virulence genes related to resistant isolates. These findings could provide insights into understanding the role of single nucleotide mutants in conferring drug resistance.

Identifying protein biomarkers in predicting disease severity of dengue virus infection using immune-related protein microarray.

Dengue virus is one of the most widespread flaviviruses that re-emerged throughout recent decades. The progression from mild dengue to severe dengue (SD) with the complications such as vascular leakage and hemorrhage increases the fatality rate of dengue. The pathophysiology of SD is not entirely clear. To investigate potential biomarkers that are suggestive of pathogenesis of SD, a small panel of serum samples selected from 1 healthy individual, 2 dengue patients without warning signs (DWS-), 2 dengue patients with warning signs (DWS+), and 5 patients with SD were subjected to a pilot analysis using Sengenics Immunome protein array. The overall fold changes of protein expressions and clustering heat map revealed that PFKFB4, TPM1, PDCL3, and PTPN20A were elevated among patients with SD. Differential expression analysis identified that 29 proteins were differentially elevated greater than 2-fold in SD groups than DWS- and DWS+. From the 29 candidate proteins, pathways enrichment analysis also identified insulin signaling and cytoskeleton pathways were involved in SD, suggesting that the insulin pathway may play a pivotal role in the pathogenesis of SD.

High dengue virus load differentially modulates human microvascular endothelial barrier function during early infection.

Plasma leakage is the main pathophysiological feature in severe dengue, resulting from altered vascular barrier function associated with an inappropriate immune response triggered upon infection. The present study investigated functional changes using an electric cell-substrate impedance sensing system in four (brain, dermal, pulmonary and retinal) human microvascular endothelial cell (MEC) lines infected with purified dengue virus, followed by assessment of cytokine profiles and the expression of inter-endothelial junctional proteins. Modelling of changes in electrical impedance suggests that vascular leakage in dengue-infected MECs is mostly due to the modulation of cell-to-cell interactions, while this loss of vascular barrier function observed in the infected MECs varied between cell lines and DENV serotypes. High levels of inflammatory cytokines (IL-6 and TNF-α), chemokines (CXCL1, CXCL5, CXCL11, CX3CL1, CCL2 and CCL20) and adhesion molecules (VCAM-1) were differentially produced in the four infected MECs. Further, the tight junctional protein, ZO-1, was down-regulated in both the DENV-1-infected brain and pulmonary MECs, while claudin-1, PECAM-1 and VE-cadherin were differentially expressed in these two MECs after infection. Non-purified virus stock was also studied to investigate the impact of virus stock purity on dengue-specific immune responses, and the results suggest that virus stock propagated through cell culture may include factors that mask or alter the DENV-specific immune responses of the MECs. The findings of the present study show that high DENV load differentially modulates human microvascular endothelial barrier function and disrupts the function of inter-endothelial junctional proteins during early infection with organ-specific cytokine production.

Next generation sequencing reveals the antibiotic resistant variants in the genome of Pseudomonas aeruginosa.

Rapid progress in next generation sequencing and allied computational tools have aided in identification of single nucleotide variants in genomes of several organisms. In the present study, we have investigated single nucleotide polymorphism (SNP) in ten multi-antibiotic resistant Pseudomonas aeruginosa clinical isolates. All the draft genomes were submitted to Rapid Annotations using Subsystems Technology (RAST) web server and the predicted protein sequences were used for comparison. Non-synonymous single nucleotide polymorphism (nsSNP) found in the clinical isolates compared to the reference genome (PAO1), and the comparison of nsSNPs between antibiotic resistant and susceptible clinical isolates revealed insights into the genome variation. These nsSNPs identified in the multi-drug resistant clinical isolates were found to be altering a single amino acid in several antibiotic resistant genes. We found mutations in genes encoding efflux pump systems, cell wall, DNA replication and genes involved in repair mechanism. In addition, nucleotide deletions in the genome and mutations leading to generation of stop codons were also observed in the antibiotic resistant clinical isolates. Next generation sequencing is a powerful tool to compare the whole genomes and analyse the single base pair variations found within the antibiotic resistant genes. We identified specific mutations within antibiotic resistant genes compared to the susceptible strain of the same bacterial species and these findings may provide insights to understand the role of single nucleotide variants in antibiotic resistance.

Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease.

BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks. METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1ß in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD). RESULTS: Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P < 0.0001; AUC = 0.819, P < 0.0001 and AUC = 0.647, P = 0.014 respectively). Furthermore, we also found that the levels of VEGF were directly correlated and sCD14 was inversely correlated with platelet count, suggesting that the endothelial activation and microbial translocation may played a role in pathogenesis of dengue disease. CONCLUSIONS: Given that the elevation IL-18, LBP and sCD14 among patients with severe form of dengue disease, our findings suggest a pathogenic role for an aberrant inflammasome and monocyte activation in the development of severe form of dengue disease.

Japanese encephalitis virus disrupts blood-brain barrier and modulates apoptosis proteins in THBMEC cells.

Japanese encephalitis (JE) is a neurotropic flavivirus that causes inflammation in central nervous system (CNS), neuronal death and also compromises the structural and functional integrity of the blood-brain barrier (BBB). The aim of this study was to evaluate the BBB disruption and apoptotic process in Japanese encephalitis virus (JEV)-infected transfected human brain microvascular endothelial cells (THBMECs). THBMECs were overlaid by JEV with different MOIs (0.5, 1.0, 5.0 and 10.0) and monitored by electrical cell-substrate impedance sensing (ECIS) in a real-time manner in order to observe the barrier function of THBMECs. Additionally, the level of 43 apoptotic proteins was quantified in the virally infected cells with different MOIs at 24h post infection. Infection of THBMEC with JEV induced an acute reduction in transendothelial electrical resistance (TEER) after viral infection. Also, significant up-regulation of Bax, BID, Fas and Fasl and down-regulation of IGFBP-2, BID, p27 and p53 were observed in JEV infected THBMECs with 0.5 and 10 MOIs compared to uninfected cells. Hence, the permeability of THBMECs is compromised during the JEV infection. In addition high viral load of the virus has the potential to subvert the host cell apoptosis to optimize the course of viral infection through deactivation of pro-apoptotic proteins.

Immune Responses to Influenza Virus and Its Correlation to Age and Inherited Factors.

Influenza viruses belong to the family Orthomyxoviridae of enveloped viruses and are an important cause of respiratory infections worldwide. The influenza virus is able to infect a wide variety species as diverse as poultry, marine, pigs, horses, and humans. Upon infection with influenza virus the innate immunity plays a critical role in efficient and rapid control of viral infections as well as in adaptive immunity initiation. The humoral immune system produces antibodies against different influenza antigens, of which the HA-specific antibody is the most important for neutralization of the virus and thus prevention of illness. Cell mediated immunity including CD4+ helper T cells and CD8+ cytotoxic T cells are the other arms of adaptive immunity induced upon influenza virus infection. The complex inherited factors and age related changes are associated with the host immune responses. Here, we review the different components of immune responses against influenza virus. Additionally, the correlation of the immune response to age and inherited factors has been discussed. These determinations lead to a better understanding of the limitations of immune responses for developing improved vaccines to control influenza virus infection.

Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3.

In our previous studies, we generated a short 13 amino acid antimicrobial peptide (AMP), DM3, showing potent antipneumococcal activity in vitro and in vivo. Here we analyse the underlying mechanisms of action using Next-Generation transcriptome sequencing of penicillin (PEN)-resistant and PEN-susceptible pneumococci treated with DM3, PEN, and combination of DM3 and PEN (DM3PEN). DM3 induced differential expression in cell wall and cell membrane structural and transmembrane processes. Notably, DM3 altered the expression of competence-induction pathways by upregulating CelA, CelB, and CglA while downregulating Ccs16, ComF, and Ccs4 proteins. Capsular polysaccharide subunits were downregulated in DM3-treated cells, however, it was upregulated in PEN- and DM3PEN-treated groups. Additionally, DM3 altered the amino acids biosynthesis pathways, particularly targeting ribosomal rRNA subunits. Downregulation of cationic AMPs resistance pathway suggests that DM3 treatment could autoenhance pneumococci susceptibility to DM3. Gene enrichment analysis showed that unlike PEN and DM3PEN, DM3 treatment exerted no effect on DNA-binding RNA polymerase activity but observed downregulation of RpoD and RNA polymerase sigma factor. In contrast to DM3, DM3PEN altered the regulation of multiple purine/pyrimidine biosynthesis and metabolic pathways. Future studies based on in vitro experiments are proposed to investigate the key pathways leading to pneumococcal cell death caused by DM3.

Suppression of ERK1/2 and hypoxia pathways by four Phyllanthus species inhibits metastasis of human breast cancer cells.

Chemotherapies remain far from ideal due to drug resistance; therefore, novel chemotherapeutic agents with higher effectiveness are crucial. The extracts of four Phyllanthus species, namely Phyllanthus niruri, Phyllanthus urinaria, Phyllanthus watsonii, and Phyllanthus amarus, were shown to induce apoptosis and inhibit metastasis of breast carcinoma cells (MCF-7). The main objective of this study was to determine the pathways utilized by these four Phyllanthus species to exert anti-metastatic activities. A cancer 10-pathway reporter was used to investigate the pathways affected by the four Phyllanthus species. Results indicated that these Phyllanthus species suppressed breast carcinoma metastasis and proliferation by suppressing matrix metalloprotein 2 and 9 expression via inhibition of the extracellular signal-related kinase (ERK) pathway. Additionally, inhibition of hypoxia-inducible factor 1-α in the hypoxia pathway caused reduced vascular endothelial growth factor and inducible nitric oxide synthase expression, resulting in anti-angiogenic effects and eventually anti-metastasis. Two-dimensional gel electrophoresis identified numerous proteins suppressed by these Phyllanthus species, including invasion proteins, anti-apoptotic protein, protein-synthesis proteins, angiogenic and mobility proteins, and various glycolytic enzymes. Our results indicated that ERK and hypoxia pathways are the most likely targets of the four Phyllanthus species for the inhibition of MCF-7 metastasis.

The impact of physical activity on cumulative cardiovascular disease risk factors among Malaysian adults.

BACKGROUND: Numerous studies have shown the importance of physical activity in reducing the morbidity and mortality rates caused by cardiovascular disease (CVD). However, most of these studies emphasise little on the cumulative effect of CVD risk factors. Hence, this study investigates the association between physical exercise and cumulative CVD risk factors among adults in three different age groups. METHODS: Using a sample of 7276 respondents drawn from community centers, the REDISCOVER team gathered information on physical activity, CVD risk factors (obesity, diabetes, hypertension, hypercholesterolemia, tobacco use) and socioeconomic and demographic variables in Malaysia. Because the study required medical examination, a convenience sampling frame was preferred in which all volunteers were included in the study. Fasting blood samples and anthropometric (height, weight and more) measurements were collected by trained staffs. Socio-demographic and physical activity variables were recorded through questionnaires. A Chi-square test was performed to identify the bivariate association between the covariates (socioeconomic variables, demographic variables and physical activity) and outcome variable. The association between the main exposure, physical activity, and the outcome variable, cumulative CVD risk factors, was assessed using an ordinal logistic regression model, controlling for socioeconomic status and demographic influences in three different age groups, 35-49, 50-64 and 65 and above. RESULTS: The mean age of participants is 51.8 (SD = 9.4). Respondents in the age groups of 35-49 (aORmoderate = 0.12; 95 % CI: 0.02 - 0.53 ) and 65 and above (aORhigh = 0.58; 95 % CI: 0.24, 0.78) showed a statistically significant inverse relationship between physical activity and cumulative CVD risk factors. However, this relationship was not significant among respondents in the 50-64 age group suggesting the possible influence of other variables, such as stress and environment. CONCLUSIONS: The statistically significant results show a negative association between physical exercise and cumulative CVD risk factors. However, the lack of a significant relationship in the 50-64 age group suggests the need to include other considerations in future studies, such as stress and environment.