Regulatory role of miRNAs in nasopharyngeal cancer involving PTEN/PI3K/AKT, TGFß/SMAD, RAS/MAPK, Wnt/ß-catenin and pRB-E2F signaling pathways: A review.

MicroRNAs (miRNA) are small and conserved noncoding RNA molecules that regulate gene expression at the posttranscriptional level. These groups of RNAs are crucial in various cellular processes, especially in mediating disease pathogenesis, particularly cancer. The dysregulation of miRNAs was reported in many cancer types, including nasopharyngeal cancer (NPC), which is a malignant tumor of the nasopharynx. In this review, miRNAs involvement in crucial signaling pathways associated with NPC such as PTEN/PI3K/AKT, TGFß/SMAD, RAS/MAPK, Wnt/ß-catenin and pRB-E2F was investigated. miRNAs could function as tumor suppressor-miR or onco-miR in NPC profoundly influenced cell cycle, apoptosis, proliferation, migration, and metastasis. This comprehensive review of current literature provided a thorough profile of miRNAs and their interplay with the aforementioned signaling pathways in NPC. Understanding these molecular interactions could remarkably impact the diagnosis, prognosis, and therapeutic strategies for NPC.

A Systematic Review on Clinico-Aetiopathological Trends of Nasopharyngeal Cancer in Asia.

BACKGROUND: Nasopharyngeal cancer (NPC) is a type of malignancy that is highly prevalent in Asian countries. Therefore, an understanding between NPC epidemiological trend, the clinico-pathological and aetiological profiles are needed. This systematic review focuses on asian countries demographic and clinico-pathological presentation reported in 9982 NPC cases diagnosed from the year 2010 to 2021. METHODOLOGY: Data were extracted from databases, such as PubMed, Springer Link, Science Direct, Google Scholar and general search engines, by using pre-determined keywords (e.g. clinico-pathological data, age, sex, tumour stage, nasopharyngeal cancer, nasopharyngeal carcinoma, naso-pharynx and cancer in Asia). RESULTS AND CONCLUSION: Findings from our systematic review shows that from 2010 to 2021, males in age range below 50 years old are at a higher risk of developing NPC in Asia. NPC is mostly diagnosed at advanced stage in Asia, which is likely due to the deep-seated location of the cancer. Type III NPC and EBV proteins (EBNA1 and LMP2A) are frequently associated with reported EBV-positive NPC cases in Asian countries. Meanwhile, NPC type I, II, and III are associated with EBV-negative NPC cases in Asia. Human leucocyte antigen (HLA) alleles (A2, B27, and B46) are frequently present in reported EBV-negative NPC cases in Asia. In Asia, males below 50 years old are more prone to NPC and often diagnosed at late stage. EBV-positive and EBV-negative NPC in Asia have unique histological profiles. Systemic approach of this study may help to provide better knowledge on reported NPC cases especially on the risk factors and clinical presentation focusing in Asian countries.

Molecular interaction analysis of anti-IL-8 scFv-10F8-6His against IL-8 monomer through molecular docking and molecular dynamic simulations.

Elevated interleukin 8 (IL-8) expression has been linked to unfavorable outcomes in a range of inflammatory conditions, such as rheumatoid arthritis, psoriasis, and cancer. The human monoclonal antibody (HuMab) 10F8 and the hybridoma 35B11-B bind to an epitope on human IL-8, respectively. 10F8 inhibited interaction between IL-8 and neutrophils in eczema and pustulosis palmoplantaris patients while 35B11-B decreased size lesion in rat model. The binding interaction of monoclonal antibodies and IL-8, especially how complementarity-determining region (CDR) loops could bind the N-terminal of IL-8, has not been fully deliberated at molecular-level. Here, we used a combination of molecular docking, heated and long coarse-grained molecular dynamics simulations to identify key residues of established interaction. Based on heated MD simulation, docked pose of complexes generated by ClusPro showed good binding stability throughout of 70 ns simulation. Based on long molecular dynamic simulations, key residues for the binding were identified throughout of 1000 ns simulation. TYR-53, ASP-99, and ARG-100 of heavy chain CDR together with TYR-33 of light chain CDR are among the highest contributing energy residues within the binding interaction. Meanwhile, LYS11 and TYR13 of IL-8 are important for the determination of overall binding energy. Furthermore, the result of decomposition residues analysis is in good agreement with the interaction analysis data. Current study provides a list of important interacting residues and further scrutiny on these residues is essential for future development and design of a new and stable recombinant antibody against IL-8.Communicated by Ramaswamy H. Sarma.

Localised Delivery of Cisplatin from Chitosan-Coated Titania Nanotube Array Nanosystems Targeting Nasopharyngeal Carcinoma.

Pupose: Cisplatin (CDDP), while amongst the recognised chemotherapeutic drugs currently available, is known to have limitations; the lack of a single treatment approach and non-specific targeted therapies. Therefore, the development of an innovative strategy that could achieve localised CDDP treatment is an urgent undertaking. Recent advances in titania nanotube arrays (TNAs) technology have demonstrated promising applications for localised chemotherapeutic drug treatment. The present work investigated the efficiency of a TNA nanosystem for the localised CDDP treatment of nasopharyngeal carcinoma (NPC). Methods: Two models of the TNA nanosystem were prepared: CDDP loaded onto the TNA nanosystem surface (CDDP-TNA) and the other consisted of chitosan-coated CDDP-TNA. CDDP release from these two nanosystems was comprehensively tested on the NPC cells NPC/HK-1 and C666-1. The NPC cytotoxicity profile of the two CDDP-TNA nanosystems was evaluated after incubation for 24, 48 and 72 hours. Intracellular damage profiles were studied using fluorescence microscopy analysis with Hoechst 33342, acridine orange and propidium iodide. Results: The half-maximal inhibitory concentrations (IC50) of CDDP at 24 hours were 0.50 mM for NPC/HK-1 and 0.05 mM for C666-1. CDDP in the CDDP-TNA and chitosan-coated CDDPTNA models presented a significant degree of NPC inhibition (P<0.05) after 24, 48 and 72 hours of exposure. The outcome revealed cellular damage and shrinkage of the cell membranes after 48 hours of exposure to CDDP-TNA. Conclusion: This in vitro work demonstrated the effectiveness of TNA nanosystems for the localised CDDP treatment of NPC cells. Further in vivo studies are needed to support the findings.

Genome-nanosurface interaction of titania nanotube arrays: evaluation of telomere, telomerase and NF-κB activities on an epithelial cell model.

Titanium dioxide nanotube arrays (TNAs) provide a promising platform for medical implants and nanomedicine applications. The present cell-TNA study has provided profound understanding on protection of genome integrity via telomere, telomerase and NF-κB activities using an epithelial cell model. It has been revealed in this study that cell-TNA interaction triggers the telomere shortening activity and inhibition of telomerase activity at the mRNA and protein level. The present work supported that the cell-TNA stimulus might involve controlled transcription and proliferative activities via NBN and TERF21P mechanisms. Moreover, inhibition of NF-κB may promote molecular sensitivity via senescence-associated secretory phenotype activities and might result in reduced inflammatory response which would be good for cell and nanosurface adaptation activities. Thus, this nanomaterial-molecular knowledge is beneficial for further nanomaterial characterization and advanced medical application.

The Association between Tea Consumption and Nasopharyngeal Cancer: A Systematic Review and Meta-Analysis

Heated debates have been on-going about tea consumption and the incidence of cancer, especially in head and neck cancer types. This study aimed to review the association between tea consumption habits and nasopharyngeal cancer (NPC). Methods: This review was carried out in accordance with the PRISMA-P protocol. Literature search for journal articles that published studies on the relationship between tea consumption and NPC was performed via databases, such as Elsevier, PubMed, Science Direct, Springer Link, Google, and Google Scholar, for 10 years from 2008 to 2018. Relevant studies were obtained by applying the pre-determined keywords, such as nasopharyngeal cancer, tea consumption and NPC, risk factors of NPC and benefits of tea consumption. Results: A total of 126 articles was retrieved. These articles were subjected to eligibility assessment. Six articles remained after applying the inclusion criteria. Results suggest that habitual tea consumption reduces NPC. Tea consumption significantly reduces NPC with all the studies having a p-value ≤0.05. Meta-analysis showed statistical association between tea consumption and NPC risk with OR=0.865 at 95% CI (0.806-0.929). Conclusion: This study suggests that habitual tea consumption could be associated with prevention of NPC development. Additional studies are needed to further understand the molecular role of bioactive compound and potential health benefit of tea consumption in NPC prevention.

Nasopharyngeal Carcinoma (NPC) Risk Factors: A Systematic Review and Meta-Analysis of the Association with Lifestyle, Diets, Socioeconomic and Sociodemographic in Asian Region.

OBJECTIVE: Risk factors of nasopharyngeal carcinoma (NPC) have been linked with diets, life style and viral
infections. NPC is more rampant in Asian populations than non-Asian countries. Our study aims to assess the validity
of the suggestions provided by multiple case control studies demonstrating that salted fish consumption, smoking and
alcohol consumption are associated with the risk of NPC in Asia. METHODS: Search for related literature on salted fish,
smoking and alcohol consumption were performed via Science Direct, PubMed databases and Google Scholar. Articles
included in this study were from 2009 to 2017, with specific focus on salted fish, smoking and alcohol consumption
as risk factors of NPC. This study excluded all articles published prior to 2009 and articles involving other cancers.
Data were extracted independently by two different researchers and harmonized. Meta-analysis was conducted on the
obtained data, by using R package Meta to create funnel and forest plots. RESULTS: The meta-analysis revealed that
salted fish, smoking and alcohol consumption were significantly associated to NPC risk with random effect model score
showing OR of 1.41 at 95% confidence interval (CI) of 1.13-1.75 (P<0.01), OR of 1.89 at 95 % CI of 1.49 - 2.38, and
OR: 1.42 at 95 % CI of 1.23 - 1.65 respectively. Our results also revealed significant association of salted meat, salted
vegetables, house type, wood dust exposure associated with NPC risk with p values less than 0.05. CONCLUSION: This
study proposes that salted fish intake, smoking and alcohol consumption might be linked to NPC risk in Asians. Further
studies are necessary to ascertain the molecular mechanisms and clarify if the associated path that could function as
therapeutic target.

Bacteriostatic Activity of LLDPE Nanocomposite Embedded with Sol⁻Gel Synthesized TiO2/ZnO Coupled Oxides at Various Ratios.

Metal oxide-polymer nanocomposite has been proven to have selective bactericidal effects against the main and common pathogens (Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli)) that can cause harmful infectious diseases. As such, this study looked into the prospect of using TiO2/ZnO with linear low-density polyethylene (LLDPE) to inactivate S. aureus and E. coli. The physical, structural, chemical, mechanical, and antibacterial properties of the nanocomposite were investigated in detail in this paper. The production of reactive species, such as hydroxyl radicals (•OH), holes (h⁺), superoxide anion radicals (O2•¯), and zinc ion (Zn2+), released from the nanocomposite were quantified to elucidate the underlying antibacterial mechanisms. LLDPE/25T75Z with TiO2/ZnO (1:3) nanocomposite displayed the best performance that inactivated S. aureus and E. coli by 95% and 100%, respectively. The dominant reactive active species and the zinc ion release toward the superior antibacterial effect of nanocomposite are discussed. This work does not only offer depiction of the effective element required for antimicrobial biomedical appliances, but also the essential structural characteristics to enhance water uptake to expedite photocatalytic activity of LLDPE/metal oxide nanocomposite for long term application.