Exosomes as the Promising Biomarker for Epstein-Barr Virus (EBV)-Associated Cancers

Exosomes are microvesicles with sizes ranging from 50 to 150 nm. These small vesicles are known to morphologically and functionally resemble virus particles from human immunodeficiency virus type I (HIV-I) and human T-lymphotropic virus type I (HTLV-I). The function of exosomes is to mainly mediate cell-to-cell communication by exchanging various macromolecules including proteins, lipids and nucleic acids in diverse cellular processes. Due to its size and structural simplicity, the transfer of pathogenic or virulent cellular factors across the cells mediated by exosomes is more efficient, hence facilitating the dissemination of viral infections and cancer diseases. The pathogenic role of exosomes in various cancers such as lung and breast, and their potentials as biomarkers have been previously studied, yet limited information is known for Epstein-Barr virus (EBV)-associated cancers. In this chapter, we discuss current evidences that support the pathogenic roles of exosomes in EBV-related cancers and their potentials as biomarkers in cancer diagnostics and therapy response. Here, we also highlight the potential challenges in the development of exosome-based biomarkers for clinical application

Non-microbial Natural Products That Inhibit Drug-Resistant Staphylococcus aureus

Drug resistance developed in human pathogenic bacteria is emerging and has become a global problem. Methicillin-resistant Staphylococcus aureus (MRSA) spreading in both hospital and community areas has posed a great impact to global public health. Current antibiotics used against these resistant strains are no longer efficacious and the search for new alternative is in urgent need. In the past decades, natural products have demonstrated multiple biological activities in biomedical areas including their antibacterial actions against various drug-resistant bacteria. More promisingly, some natural products could reverse the resistance of bacteria to the antibiotics, making the target bacteria susceptible to these drugs again. Numerous natural products have also exhibited potent synergism against the drug-resistant bacteria when used in combination with various types of antibiotics. Recently, several antibacterials derived from microbes have been developed and approved by Food and Drug Administration (FDA) for clinical use. In this chapter, we discuss the potential use of non-microbial natural products in controlling Staphylococcus aureus (S. aureus)‘s growth, and the underlying challenges in developing the natural products into clinical applications

Epstein-Barr Virus as a promising immunotherapeutic target for nasopharyngeal carcinoma treatment

Epstein-Barr virus (EBV) is a pathogen that infects more than 90% of global human population. EBV primarily targets Blymphocytes and epithelial cells while some of them infect monocyte/macrophage, T-lymphocytes, and dendritic cells (DCs). EBV infection does not cause death by itself but the infection has been persistently associated with certain type of cancers such as nasopharyngeal carcinoma (NPC), Burkitt’s lymphoma (BL), and Hodgkin’s lymphoma (HL). Recent findings have shown promise on targeting EBV proteins for cancer therapy by immunotherapeutic approach. Some studies have also shown the success of adopting EBV-based therapeutic vaccines for the prevention of EBV-associated cancer particularly on NPC. In-depth investigations are in progress to refine the current therapeutic and vaccination strategies. In present review, we discuss the highly potential EBV targets for NPC immunotherapy and therapeutic vaccine development aswell as addressing the underlying challenges in the process of bringing the therapy and vaccination from the bench to bedside

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

Novel genetic variants of Hepatitis B Virus in fulminant hepatitis

Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%),K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%).We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH

Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review

Curcumin, the major constituent of Curcuma longa L. (Zingiberaceae family) or turmeric, commonly used for cooking in Asian cuisine, is known to possess a broad range of pharmacological properties at relatively nontoxic doses. Curcumin is found to be effective against Staphylococcus aureus (S. aureus). As demonstrated by in vitro experiment, curcumin exerts even more potent effects when used in combination with various other antibacterial agents. Hence, curcumin which is a natural product derived fromplant is believed to have profoundmedicinal benefits and could be potentially developed into a naturally derived antibiotic in the future. However, there are several noteworthy challenges in the development of curcumin as a medicine. S. aureus infections, particularly those caused by themultidrug-resistant strains, have emerged as a global health issue and urgent action is needed.This review focuses on the antibacterial activities of curcumin against both methicillin-sensitive S. aureus (MSSA) and methicillinresistant S. aureus (MRSA). We also attempt to highlight the potential challenges in the effort of developing curcumin into a therapeutic antibacterial agent

High expression of LC3A, LC3B, and p62/SQSTM1 autophagic proteins in human colonic ganglion cells

Introduction: Autophagy is a mechanism that degrades large damaged organelles and misfolded proteins to maintain the homeostasis in all cells. It plays double-faceted roles in tumourigenesis and prevention of various cancers. In our side observation of investigating the prognostic value of autophagy in colorectal cancer (CRC), we found high expression of autophagy proteins (LC3A, LC3B, and p62/SQSTM1) in the colonic ganglion cells. To our best understanding, this is the first paper reporting such finding. Materials and Methods: Formalin-fixed paraffin-embedded (FFPE) CRC tissues blocks were retrieved and confirmed by haematoxylin & eosin (H&E) staining. Immunohistochemistry (IHC) targeting autophagy proteins (LC3A, LC3B, and p62/SQSTM1) was then performed followed by pathological examination. Results: All three autophagy proteins were present in both normal and tumour tissues of CRC patients. Interestingly, high expression of autophagy proteins in colonic ganglion cells was consistently seen regardless of tissue type (normal or cancer) or tumour site (caecum, ascending, transverse, descending, sigmoid colon and rectum). Conclusions: This work highlights the high autophagic activities in human colonic ganglion cells

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

Profiling of serum and tissue high abundance acute-phase proteins of patients with epithelial and germ line ovarian carcinoma

<p>Abstract</p> <p>Background</p> <p>Acute-phase response involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or malignancy. Studies of the acute-phase response usually involve determination of the levels of individual acute-phase serum proteins. In the present study, the acute-phase response of patients with epithelial (EOCa) and germ-line (GOCa) ovarian carcinoma was investigated using the gel-based proteomic approach, a technique which allowed the simultaneous assessment of the levels of the acute-phase serum high abundance proteins. Data obtained were validated using ELISA and immunostaining of biopsy samples.</p> <p>Results</p> <p>Enhanced expression of clusterin (CLU), α₁-antitrypsin, haptoglobin and leucine rich glycoprotein was detected in all patients. However, the levels of α₁-antichymotrypsin (ACT) was only enhanced in EOCa patients, while patients with GOCa were typically characterized by elevated levels of ceruloplasmin but lower levels of α₂-HS glycoprotein. The enhanced expression of CLU in EOCa and GOCa patients and up-regulated expression of ACT specifically in EOCa patients were confirmed by ELISA. Immunohistochemical staining of biopsy samples of EOCa and GOCa patients demonstrated correlation of the acute-phase protein expression.</p> <p>Conclusion</p> <p>Patients with EOCa and GOCa demonstrated distinctive aberrant expression of serum and tissue high abundance acute-phase proteins compared to negative control women.</p