Expression of LC3A, LC3B and p62/SQSTM1 autophagy proteins in hepatocellular carcinoma (HCC) tissues and the predicted microRNAs involved in the autophagy-related pathway.

BACKGROUND: Autophagy plays multifaceted roles in regulating hepatocellular carcinoma (HCC) and the mechanisms involved are under-explored. Regulatory microRNAs (miRNAs) have been reported to target autophagy proteins but their roles in HCC is not well studied. Using HCC patient tissues, this study aims to investigate the association of autophagy with several clinicopathological parameters as well as identifying the autophagy-related miRNAs and the possible pathways. METHODS AND RESULTS: Autophagy level in the HCC patient-derived cancer and non-cancer tissues was determined by immunohistochemistry (IHC) targeting SQSTM1, LC3A and LC3B proteins. Significance tests of clinicopathological variables were tested using the Fisher's exact or Chi-square tests. Gene and miRNA expression assays were carried out and analyzed using Nanostring platform and software followed by validation of other online bioinformatics tools, namely String and miRabel. Autophagy expression was significantly higher in cancerous tissues compared to adjacent non-cancer tissues. High LC3B expression was associated with advanced tumor histology grade and tumor location. Nanostring gene expression analysis revealed that SQSTM1, PARP1 and ATG9A genes were upregulated in HCC tissues compared to non-cancer tissues while SIRT1 gene was downregulated. These genes are closely related to an autophagy pathway in HCC. Further, using miRabel tool, three downregulated miRNAs (hsa-miR-16b-5p, hsa-miR-34a-5p, and hsa-miR-660-5p) and one upregulated miRNA (hsa-miR-539-5p) were found to closely interact with the abovementioned autophagy-related genes. We then mapped out the possible pathway involving the genes and miRNAs in HCC tissues. CONCLUSIONS: We conclude that autophagy events are more active in HCC tissues compared to the adjacent non-cancer tissues. We also reported the possible role of several miRNAs in regulating autophagy-related genes in the autophagy pathway in HCC. This may contribute to the development of potential therapeutic targets for improving HCC therapy. Future investigations are warranted to validate the target genes reported in this study using a larger sample size and more targeted molecular technique.

Association of Fusobacterium nucleatum infection with the clinicopathological characteristics in colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) is a global health problem. The gut microbiome is now recognized as an important underlying factor to the initiation and progression of CRC. Fusobacterium nucleatum (FN) is one of the most studied bacteria in the aetiology of CRC. This study provided cohort evidence on the association of FN infection with clinicopathologic features in CRC patients. METHODS: We analysed the cancerous and adjacent non-cancerous formalin-fixed paraffin embedded (FFPE) tissue of 83 CRC patients from a single medical centre in Malaysia. TaqMan probe-based qPCR targeting the 16S rRNA gene was used to detect the presence of FN in the extracted FFPE DNA. The differences in FN expression between cancer and non-cancer tissues were evaluated. Association studies between FN infection in the tumour and relative FN abundance with available clinical data were conducted. RESULTS: FN was more abundant in the cancerous tissue compared to non-cancerous tissue (p = 0.0025). FN infection in the tumour was significantly associated with lymph node metastasis (p = 0.047) and cancer staging (p = 0.032), but not with other clinicopathologic variables. In double-positive patients where FN was detected in both cancerous and non-cancerous tissue, the expression fold-change of FN, calculated using 2-ΔΔCT formula, was significantly higher in patients with tumour size equal to or greater than 5 cm (p = 0.033) and in KRAS-mutated patients (p = 0.046). CONCLUSIONS: FN is enriched in CRC tumour tissue and is associated with tumour size, lymph node metastasis, cancer staging, and KRAS mutation in this single-centre small cohort study.

Low dose and low dose rate radioluminescence dosimetry.

Review is provided of a number of low-dose, low dose rate situations that in study require advances in the development of dosimetric facilities. Using a clinical linac set up to provide doses down to the few mGy level, the performance of a real-time radioluminescence system has then been illustrated, accommodating pulsed as well as continuous dose delivery. The system gate times provide for tracking of the pattern of dose delivery, allowing detailed account of dose and dose-rate variations. The system has been tested in both x-ray and electron mode dose delivery.

Knowledge of Sarcopenia and Associated Factors Among the Malaysian General Public: A Cross-sectional Study / 예방의학회지

Objectives@#Sarcopenia has emerged as a significant aging-related disease that affects many facets of societal-level and patient-level public health. This study analysed knowledge of sarcopenia and associated socio-demographic factors among the general public of Malaysia in order to effectively improve its prevention and countermeasures. @*Methods@#A cross-sectional online survey was conducted in Selangor, Malaysia, using Google Forms among 202 Malaysian adults from January 1, 2021 to March 31, 2021. Descriptive statistics were used to analyse the socio-demographic characteristics and knowledge scores. The continuous variables were evaluated using the independent t-test, Mann–Whitney test, and one-way analysis of variance test. The Spearman correlation coefficient was employed to determine the correlation between socio-demographic characteristics and knowledge score levels. @*Results@#The final analysis included 202 participants. The mean±standard deviation age was 49.03±12.65. Only 6.9% of participants had good knowledge of sarcopenia and were aware of sarcopenia’s characteristics, consequences, and treatments. Post-hoc comparisons using the Dunnett T3 test showed statistical significance in mean knowledge score and age group (p=0.011) and education level (p≤0.001). The Mann–Whitney test revealed that gender (p=0.026) and current smoking status (p=0.023) significantly influenced knowledge scores. @*Conclusions@#The general public’s knowledge of sarcopenia was found to be poor to moderate and associated with age and education status. Therefore, education and interventions by policymakers and healthcare professionals to improve public knowledge of sarcopenia in Malaysia are needed.

Patient-related factors associated with medication adherence behavior in patients with end-stage renal disease: A systematic review.

Objectives: This systematic review aims to identify influencing factors of medication adherence behavior in patients with end-stage renal disease (ESRD), with a special interest in patient-related factors based on the World Health Organization adherence model. Materials and Methods: Primary electronic databases comprising PubMed, Scopus, Web of Science, Embase and Cochrane Library, as well as ProQuest (Health and Medical), ProQuest (Psychology), and EBSCOHost (APA PsychARTICLES) were used to search for literature on patient-related factors in medication adherence, from inception till August 31, 2021. Results: 479 articles were identified and six articles meeting eligibility criteria were reviewed and remained in this systematic review. The present review found that despite different tools being used to measure ESRD's perception of medication's necessity and beliefs, there was a profound association between perception and beliefs with medication adherence behavior. There is a positive relationship between knowledge, belief, educational level, ethnicity, female, and medication adherence behavior. Mixed finding was reported between perception, age, and medication adherence behavior. However, there were no studies on patients' attitudes and medication adherence behavior as suggested in the WHO adherence model. Conclusion: Only a limited number of patient-related factors were available for evaluation in the current systematic review. Additional research is needed to advance the understanding of medication adherence behavior affected by patient-related factors on the medication and illness. However, the findings must be taken with caution because of the limited studies included in this review.

Hepatitis B virus DNA methylation and its potential role in chronic hepatitis B.

Hepatitis B virus (HBV) infection led to 66% liver deaths world-wide in year 2015. Thirty-seven per cent of these deaths were the result of chronic hepatitis B (CHB)-associated hepatocellular carcinoma (HCC). Although early diagnosis of HCC improves survival, early detection is rare. Methylation of HBV DNA including covalently closed circular DNA (cccDNA) is more often encountered in HCC cases than those in CHB and cirrhosis. Three typical CpG islands within the HBV genome are the common sites for methylation. The HBV cccDNA methylation affects the viral replication and protein expression in the course of infection and may associate with the disease pathogenesis and HCC development. We review the current findings in HBV DNA methylation that provide insights into its role in HCC diagnosis.

Insights into Controlling the Spread of COVID-19: A Study Inspired by Seven of the Earliest Vaccinated Countries.

Background: The aim of the study is to derive deeper insights into the control of the spread of COVID-19 during the second half of 2021, from seven countries that are among the earliest to have accelerated the deployment of COVID-19 vaccines. Methodology. This study used data from the Global COVID-19 Index and Google COVID-19 Community Mobility Reports. Data was extracted on the 5th of each month from July to December 2021. Seven countries were selected-United Kingdom, United States of America, Israel, Canada, France, Italy, and Austria. The sample comprised number of new cases, hospitalisations, ICU admissions and deaths due to COVID-19, government stringency measures, partial and full vaccination coverage, and changes in human mobility. Principal component analysis was conducted, and the results were interpreted and visualized through 2-dimensional and 3-dimensional plots to reveal the systematic patterns of the data. Results: The first three principal components captured around 77.3% of variance in the data. The first component was driven by the spread of COVID-19 (31.6%), the second by mobility activities (transit, retail, and recreational) (24.3%), whereas the third by vaccination coverage, workplace-related mobility, and government stringency measures (21.4%). Visualizations showed lower or moderate levels of severity in COVID-19 during this period for most countries. By contrast, the surge in the USA was more severe especially in September 2021. Human mobility activities peaked in September for most countries and then receded in the following months as more stringent government measures were imposed, and countries began to grapple with a surge in COVID-19 cases. Conclusion: This study delineated the spread of COVID-19, human mobility patterns, widespread vaccination coverage, and government stringency measures on the overall control of COVID-19. While at least moderate levels of stringency measures are needed, high vaccine coverage is particularly important in curbing the spread of this disease.

COVID-19 vaccine hesitancy and its associated factors in Malaysia.

The success of the COVID-19 vaccination programme to achieve herd immunity depends on the proportion of the population inoculated. COVID-19 vaccination hesitancy is a barrier to reaching a sufficient number of people to achieve herd immunity. This study aims to determine the prevalence of COVID-19 vaccine hesitancy and to identify the reasons contributing to vaccine hesitancy using the Theory of Planned Behavior. A cross-sectional online survey was conducted between May 2021 to June 2021. Using exponential non-discriminative snowball sampling, participants were recruited via social media and telecommunication platforms. We used a questionnaire that obtained information on participant socio-demographics, vaccine hesitancy, pseudoscientific practices, conspiracy beliefs, subjective norms, perceived behavioural control, main reasons for not intending to get the COVID-19 vaccine; influential leaders, gatekeepers and anti-or pro-vaccination lobbies; and global vaccine hesitancy. A total of 354 responses (mean age = 32.5 years old ±13.6; 70.3% females) were included for analysis. The prevalence of COVID-19 vaccine hesitancy was 11.6%. COVID-19 vaccine hesitancy was significantly and positively associated with those who agreed with influential leaders, gatekeepers, and anti- or pro-vaccination lobbies (adjusted B coefficient = 1.355, p = 0.014), having a "wait and see" attitude to see if the COVID-19 vaccine is safe (adjusted B coefficient = 0. 822, p <0.001), perceiving that the vaccine will give them COVID-19 (adjusted B coefficient = 0.660, p <0.002), planned to use masks/others precautions instead (adjusted B coefficient = 0.345, p = 0.038) and having higher scores in conspiracy beliefs (adjusted B coefficient = 0.128, p <0.001). Concern about the costs associated with the vaccine (adjusted B coefficient = -0.518, p <0.001), subjective norms (adjusted B coefficient = -0.341, p <0.001), and perceived behavioural control (adjusted B coefficient = -0.202, p = 0.004) were negatively associated with vaccine hesitancy. COVID-19 vaccine hesitancy in Malaysia is low. Several factors were identified as being associated with vaccine hesitancy. Factors associated with vaccine hesitancy would be useful in tailoring specific interventions involving positive messages by influential leaders, which address vaccine misinformation and the wait-and-see attitude which may delay the uptake of COVID-19 vaccines.

Genetic variations in methotrexate metabolic pathway genes influence methotrexate responses in rheumatoid arthritis patients in Malaysia.

Methotrexate (MTX) is the most widely used disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). Many studies have attempted to understand the genetic risk factors that affect the therapeutic outcomes in RA patients treated with MTX. Unlike other studies that focus on the populations of Caucasians, Indian and east Asian countries, this study investigated the impacts of six single nucleotide polymorphisms (SNPs) that are hypothesized to affect the outcomes of MTX treatment in Malaysian RA patients. A total of 647 RA patients from three ethnicities (NMalay = 153; NChinese = 326; NIndian = 168) who received MTX monotherapy (minimum 15 mg per week) were sampled from three hospitals in Malaysia. SNPs were genotyped in patients using TaqMan real-time PCR assay. Data obtained were statistically analysed for the association between SNPs and MTX efficacy and toxicity. Analysis of all 647 RA patients indicated that none of the SNPs has influence on either MTX efficacy or MTX toxicity according to the Chi-square test and binary logistic regression. However, stratification by self-identified ancestries revealed that two out of six SNPs, ATIC C347G (rs2372536) (OR 0.5478, 95% CI 0.3396-0.8835, p = 0.01321) and ATIC T675C (rs4673993) (OR 0.5247, 95% CI 0.3248-0.8478, p = 0.008111), were significantly associated with MTX adequate response in RA patients with Malay ancestry (p < 0.05). As for the MTX toxicity, no significant association was identified for any SNPs selected in this study. Taken all together, ATIC C347G and ATIC T675C can be further evaluated on their impact in MTX efficacy using larger ancestry-specific cohort, and also incorporating high-order gene-gene and gene-environment interactions.

The lived experiences of a COVID-19 immunization programme: vaccine hesitancy and vaccine refusal.

BACKGROUND: The COVID-19 pandemic has resulted in a global health emergency and lock-down measures to curb the uncontrolled transmission chain. Vaccination is an effective measure against COVID-19 infections. In Malaysia amidst the national immunisation programme (NIP) which started in February 2021, there were rising concerns regarding the prevalence of vaccine hesitancy and refusal, and therefore, vaccine uptake among Malaysians. Although there are many quantitative studies on COVID-19 vaccination, the subjective experience of individuals was understudied. This study aims to explore the lived experiences of Malaysians regarding vaccine hesitancy and refusal, and facilitating factors that could enhance vaccine acceptance and uptake. METHODS: This qualitative study employed the hermeneutic phenomenological study design. Purposive sampling strategies were used to recruit Malaysians that had direct experiences with friends, family members and their community who were hesitating or refusing to accept the COVID-19 vaccines. A semi-structured interview guide was developed based on the expert knowledge of the investigators and existing literature on the topic. A series of focus group interviews (FGIs) was conducted online facilitated by a multidisciplinary team of experts. The group interviews were transcribed verbatim and analysed. RESULTS: Fifty-nine participants took part in seven FGIs. We found that "incongruence" was the overall thematic meaning that connected all the 3 main themes. These themes comprise firstly, the incongruence between the aims and implementation of the National Immunization Program which highlighted the gap between realities and needs on the ground. Secondly, the incongruence between Trust and Mistrust revealed a trust deficit in the government, COVID-19 news, and younger people's preference to follow the examples of local vaccination "heroes". Thirdly, the incongruence in communication showed the populace's mixed views regarding official media and local social media. CONCLUSIONS: This study provided rich details on the complex picture of the COVID-19 immunization program in Malaysia and its impact on vaccine hesitancy and refusal. The inter-related and incongruent factors explained the operational difficulty and complexity of the NIP and the design of an effective health communication campaign. Identified gaps such as logistical implementation and communication strategies should be noted by policymakers in implementing mitigation plans.

Multivariate visualization of the global COVID-19 pandemic: A comparison of 161 countries.

BACKGROUND: The aim of the study was to visualize the global spread of the COVID-19 pandemic over the first 90 days, through the principal component analysis approach of dimensionality reduction. METHODS: This study used data from the Global COVID-19 Index provided by PEMANDU Associates. The sample, representing 161 countries, comprised the number of confirmed cases, deaths, stringency indices, population density and GNI per capita (USD). Correlation matrices were computed to reveal the association between the variables at three time points: day-30, day-60 and day-90. Three separate principal component analyses were computed for similar time points, and several standardized plots were produced. RESULTS: Confirmed cases and deaths due to COVID-19 showed positive but weak correlation with stringency and GNI per capita. Through principal component analysis, the first two principal components captured close to 70% of the variance of the data. The first component can be viewed as the severity of the COVID-19 surge in countries, whereas the second component largely corresponded to population density, followed by GNI per capita of countries. Multivariate visualization of the two dominating principal components provided a standardized comparison of the situation in the161 countries, performed on day-30, day-60 and day-90 since the first confirmed cases in countries worldwide. CONCLUSION: Visualization of the global spread of COVID-19 showed the unequal severity of the pandemic across continents and over time. Distinct patterns in clusters of countries, which separated many European countries from those in Africa, suggested a contrast in terms of stringency measures and wealth of a country. The African continent appeared to fare better in terms of the COVID-19 pandemic and the burden of mortality in the first 90 days. A noticeable worsening trend was observed in several countries in the same relative time frame of the disease's first 90 days, especially in the United States of America.

Interplay of autophagy and cancer stem cells in hepatocellular carcinoma.

Liver cancer is the sixth most common cancer and the fourth leading cause of cancer deaths in the world. The most common type of liver cancers is hepatocellular carcinoma (HCC). Autophagy is the cellular digestion of harmful components by sequestering the waste products into autophagosomes followed by lysosomal degradation for the maintenance of cellular homeostasis. The impairment of autophagy is highly associated with the development and progression of HCC although autophagy may be involved in tumour-suppressing cellular events. In regards to its protecting role, autophagy also shelters the cells from anoikis- a programmed cell death in anchorage-dependent cells detached from the surrounding extracellular matrix which facilitates metastasis in HCC. Liver cancer stem cells (LCSCs) have the ability for self-renewal and differentiation and are associated with the development and progression of HCC by regulating stemness, resistance and angiogenesis. Interestingly, autophagy is also known to regulate normal stem cells by promoting cellular survival and differentiation and maintaining cellular homeostasis. In this review, we discuss the basal autophagic mechanisms and double-faceted roles of autophagy as both tumour suppressor and tumour promoter in HCC, as well as its association with and contribution to self-renewal and differentiation of LCSCs.

Colon Carcinogenesis: The Interplay Between Diet and Gut Microbiota.

Colorectal cancer (CRC) incidence increases yearly, and is three to four times higher in developed countries compared to developing countries. The well-known risk factors have been attributed to low physical activity, overweight, obesity, dietary consumption including excessive consumption of red processed meats, alcohol, and low dietary fiber content. There is growing evidence of the interplay between diet and gut microbiota in CRC carcinogenesis. Although there appears to be a direct causal role for gut microbes in the development of CRC in some animal models, the link between diet, gut microbes, and colonic carcinogenesis has been established largely as an association rather than as a cause-and-effect relationship. This is especially true for human studies. As essential dietary factors influence CRC risk, the role of proteins, carbohydrates, fat, and their end products are considered as part of the interplay between diet and gut microbiota. The underlying molecular mechanisms of colon carcinogenesis mediated by gut microbiota are also discussed. Human biological responses such as inflammation, oxidative stress, deoxyribonucleic acid (DNA) damage can all influence dysbiosis and consequently CRC carcinogenesis. Dysbiosis could add to CRC risk by shifting the effect of dietary components toward promoting a colonic neoplasm together with interacting with gut microbiota. It follows that dietary intervention and gut microbiota modulation may play a vital role in reducing CRC risk.

C-MYC, BCL2 and BCL6 Translocation in B-cell Non-Hodgkin Lymphoma Cases.

C-MYC, BCL2 and BCL6 genes are the most commonly oncogenes involved in B-Cell lymphomas. Translocations of these oncogenes are associated with an aggressive clinical course. This study aims to elucidate the patterns of BCL6, BCL2 and C-MYC gene aberrations among Malaysian B-cell Non-Hodgkin Lymphoma (NHL) using fluorescence in situ hybridization (FISH). Eighty-one B-cell NHL tissue blocks were retrieved between the year 2011 to 2015 and investigated using immunohistochemistry and interphase FISH dual colour break-apart probes of BCL2, BCL6, C-MYC and IgH. A significant difference was detected between the nodal and extranodal sites in all the BCL2 (p=0.01), C-MYC (p=0.03) and IgH (p=0.006) cases except for BCL6 (p=0.2). Our study showed that BCL6 had the highest gene translocation while BCL2/BCL6 had the most mixed aberrations of gain copies and translocation, however no mixed aberrations of gain copies and translocation was found in C-MYC. None of the mixed gain copies and translocation was found in any of the germinal centre B-cell (GCB) subtype of Diffuse Large B-cell Lymphoma, however, five were found in BCL6 and IgH gene in the non-GCB subtype; while mixed gain copies and translocation cases of BCL2 gene was found in the Follicular Lymphoma cases only. The study found interesting findings of BCL2, C-MYC and IgH gene aberrations between nodal and extranodal sites. This information might benefit future study in predicting prognosis and determine effective therapeutic strategies in the multi-ethnic populations of Malaysia as well as the Asian population.

Current Update of Laboratory Molecular Diagnostics Advancement in Management of Colorectal Cancer (CRC).

Colorectal cancer (CRC) continues to be one of the most common cancers globally. The incidence has increased in developing countries in the past few decades, this could be partly attributed to aging populations and unhealthy lifestyles. While the treatment of CRC has seen significant improvement since the advent of target-specific therapies and personalized medicine, CRC is oftentimes detected at late or advanced stages, thereby reducing the efficacy of treatment. Hence, screening for early detection is still the key to combat CRC and to increase overall survival (OS). Considering that the field of medical diagnostics is moving towards molecular diagnostics, CRC can now be effectively screened and diagnosed with high accuracy and sensitivity. Depending on the tumor genotype and genetic profile of the individual, personalized treatments including tyrosine kinase inhibitor therapy and immunotherapy can be administered. Notably, there can be no one single treatment that is effective for all CRC patients due to the variation in tumor genetics, which highlights the importance of molecular diagnostics. This review provides insights on therapeutic modalities, molecular biomarkers, advancement of diagnostic technologies, and current challenges in managing CRC.

Green fabrication of biologically active magnetic core-shell Fe3O4/Au nanoparticles and their potential anticancer effect.

Core-shell Fe3O4/Au nanostructures were constructed using an advanced method of two-step synthesis from Juglans regia (walnut) green husk extract. Several complementary methods were applied to investigate structural and magnetic properties of the samples. X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), electron diffraction, optical, thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM) were used for nanoparticle characterizations. As shown by HR-TEM, the mean diameter of core-shell Fe3O4/Au nanoparticles synthesized using co-precipitation method was 6.08 ±â€¯1.06 nm. This study shows that the physical and structural properties of core-shell Fe3O4/Au nanoparticles possess intrinsic properties of gold and magnetite. VSM revealed that the core-shell Fe3O4/Au have high saturation magnetization and low coercivity due to the magnetic properties. The core-shell nanoparticles show the inhibitory concentration (IC)50 of 235 µg/ml against a colorectal cancer cell line, HT-29. When tested against non-cancer cells, IC50 was not achieved even up to 500 µg/ml. This study highlights the magnetic properties and anticancer action of core-shell Fe3O4/Au nanoparticles. This compound can be ideal candidate for cancer treatment and other biomedical applications.

Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development.

Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission. RA is strongly associated with various immune cells and each of the cell type contributes differently to the disease pathogenesis. Several types of immunomodulatory molecules mainly cytokines secreted from immune cells mediate pathogenesis of RA, hence complicating the disease treatment and management. There are various treatments for RA depending on the severity of the disease and more importantly, the patient's response towards the given drugs. Early diagnosis of RA and treatment with (DMARDs) are known to significantly improve the treatment outcome of patients. Sensitive biomarkers are crucial in early detection of disease as well as to monitor the disease activity and progress. This review aims to discuss the pathogenic role of various immune cells and immunological molecules in RA. This review also highlights the importance of understanding the immune cells in treating RA and in exploring novel biomarkers.

Bactericidal Properties of Plants-Derived Metal and Metal Oxide Nanoparticles (NPs).

Nanoparticles (NPs) are nano-sized particles (generally 1⁻100 nm) that can be synthesized through various methods. The wide range of physicochemical characteristics of NPs permit them to have diverse biological functions. These particles are versatile and can be adopted into various applications, particularly in biomedical field. In the past five years, NPs' roles in biomedical applications have drawn considerable attentions, and novel NPs with improved functions and reduced toxicity are continuously increasing. Extensive studies have been carried out in evaluating antibacterial potentials of NPs. The promising antibacterial effects exhibited by NPs highlight the potential of developing them into future generation of antimicrobial agents. There are various methods to synthesize NPs, and each of the method has significant implication on the biological action of NPs. Among all synthetic methods, green technology is the least toxic biological route, which is particularly suitable for biomedical applications. This mini-review provides current update on the antibacterial effects of NPs synthesized by green technology using plants. Underlying challenges in developing NPs into future antibacterials in clinics are also discussed at the present review.

Pathogenic Role of Exosomes in Epstein-Barr Virus (EBV)-Associated Cancers.

Exosomes are 40- to 100-nm membrane-bound small vesicles that carry a great variety of cellular cargoes including proteins, DNA, messenger RNAs (mRNAs), and microRNAs (miRNAs). These nanovesicles are detected in various biological fluids such as serum, urine, saliva, and seminal fluids. Exosomes serve as key mediators in intercellular communication by facilitating the transfer and exchange of cellular components from cells to cells. They contain various pathogenic factors whereby their adverse effects have been implicated in multiple viral infections and cancers. Interestingly, accumulating evidences showed that exosomes derived from tumour viruses or oncoviruses, exacerbate virus-associated cancers by remodelling the tumour microenvironment. In this review, we summarize the contributing factors of Epstein-Barr virus (EBV) products-containing exosomes in viral pathogenesis and their potential implications in EBV-driven malignancies. Understanding the biological role of these exosomes in the disease would undoubtedly boost the development of a more comprehensive strategy to combat EBV-associated cancers and to better predict the therapeutic outcomes. Furthermore, we also highlight the potentials and challenges of EBV products-containing exosomes being employed as diagnostic markers and therapeutic targets for EBV-related cancers. Since these aspects are rather underexplored, we attempt to underline interesting areas that warrant further investigations in the future.

CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma.

Subpopulations of nasopharyngeal carcinoma (NPC) contain cells with differential tumourigenic properties. Our study evaluates the tumourigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in NPC. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumourigenic cells leading to tumours with larger volume and higher mitotic figures. Although CD44br and EpCAMbr cells significantly enriched for tumour-initiating cells (TICs), all cells could retain self-renewal property for at least four generations. Compared to CD44 marker alone, EpCAM/CD44dbr marker did not enhance for cells with faster-growing ability or higher TIC frequency. Cells expressing high CD44 or EpCAM had lower KLF4 and p21 in NPC subpopulations. KLF4-overexpressed EpCAMbr cells had slower growth while Kenpaullone inhibition of KLF4 transcription increased in vitro cell proliferation. Compared to non-NPC, NPC specimens had increased expression of EPCAM, of which tumours from advanced stage of NPC had higher expression. Together, our study provides evidence that EpCAM is a potentially important marker in NPC.