Antibiofilm and antiadhesion activities of phaleria macrocarpa extracts against streptococcus mutans

Dental caries is a major concern in oral healthcare. Continuous researches have been performedextensively in finding new compounds that are capable to solve the problems. Phaleria macrocarpa has been identified effective against hypertension, diabetic, cancer, and diuretic acid. In this study, antiadhesion and antibiofilm activities of Stretococcus mutans were investigated using crude extracts of fruit, leaf and stem of P. macrocarpa. Minimal inhibitory concentration (MIC) assay was conducted to identify the lowest concentration of the extracts required to suppress the activity of S. mutans. This assay confirmed that all tested extracts were able to inhibit the bacterial activities with concentration of less than 8 mg/mL and thus can be classified as natural antimicrobial agents. The extracts were found capable of reducing 50 to 80% of both adhesion and biofilm activity of S. mutans at 1.56 mg/ml. Results from this study provide a preliminary data for the effectiveness of P. macrocarpa crude extracts as antiadhesion and antibiofilm agent against S. Mutans and may have potential for antiseptic agent to treat oral dental caries

LEP G2548A polymorphism is associated with increased serum leptin and insulin resistance among T2DM Malaysian patients

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome that is rapidly increasing across the world, especially in Malaysia. Leptin plays a vital role in the regulation of metabolism through its effect on peripheral tissues. G2548A polymorphism in the LEP gene promoter has been associated with insulin resistance, leptin, and type 2 diabetes mellitus across different population, but has not been inclusively reported within the Malaysian population. Objective: Thus, our study aimed to investigate the impact of G2548A polymorphism on serum leptin levels and insulin resistance among Malaysian T2DM patients. Methods: This case-control study involved 150 T2DM patients and 150 non-diabetic volunteers from ethnic Malays, Chinese and Indians. Genotyping of G2548A polymorphism was carried out using PCR-RFLP. Serum leptin and insulin levels were determined via ELISA. ANOVA and Chi-square tests were used to determine the distribution of genotypes and allelic frequencies based on serum leptin and insulin levels. Results: Frequency of AA genotype and A allele of G2548A variant were significantly (P < 0.05) higher in T2DM patients of Malay and Indian ethnicities (4%, 35%, and 36%, 57%, respectively) as compared to the control groups (0%, 22%, and 18%, 35%, respectively). Fasting serum leptin levels were significantly (P < 0.001) higher in T2DM patients compared to non-diabetic subjects (166.78 pg/ml, 101.94 pg/ml, respectively). Additionally, elevated serum leptin, insulin levels, and BMI in diabetic patients were found to be associated with the AA genotype of this variant, compared to GG, and GA genotypes (P < 0.05). Conclusion: Our findings suggest a significant association between G2548A polymorphism among Malaysian T2DM subjects, particularly among Malay and Indian ethnic groups. Moreover, the A allele frequency of the G2548A variant significantly increased the risk of T2DM and is significantly associated with increased serum leptin, insulin levels, and elevated BMI

Alleviation of diabetic nephropathy by zinc oxide nanoparticles in streptozotocin‐induced type 1 diabetes in rats

Abstract This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end‐stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24‐h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor‐β1, fibronectin, collagen‐IV, tumour necrosis factor‐α and vascular endothelial growth factor‐A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase‐9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy

In vivo evaluation of oxidized multiwalled-carbon nanotubes-mediated hyperthermia treatment for breast cancer

Breast cancer is one of the most common types of cancer that contribute to high mortality worldwide. Hyperthermia (HT) was introduced as one of the alternative treatments to treat breast cancer but has major drawback of damaging normal adjacent cells. This study explores the integration effect of multiwalled-carbon nanotubes (MWCNTs) in combination with hyperthermia treatment for breast cancer therapy regimes. In this study, acid-functionalized MWCNTs (ox-MWCNTs) were prepared by acid washing methods using H2SO4/HNO3 (98%/68%) with the ratio of 3:1 (?/?) and characterized by colloidal dispersibility test, FTIR, TGA, XRD, FESEM and EDX analysis. EMT6 tumor-bearing mice were treated with ox-MWCNTs in combination with local HT at 43 °C. The tumor progression was monitored and the influence of immune response was evaluated. Results from this study demonstrated that mice from ox-MWCNTs in combination with local HT treatment group experienced complete tumor eradication, accompanied by a significant increase in median survival of the mice. Histological and immunohistochemical analysis of tumor tissues revealed that tumor treated with combined treatment underwent cell necrosis and there was a significant reduction of proliferating cells when compared to the untreated tumor. This observation is also accompanied with an increase in Hsp70 expression in tumor treated with HT. Flow cytometry analysis of the draining lymph nodes showed an increase in dendritic cells infiltration and maturation in mice treated with combined treatment. In addition, a significant increase of tumor-infiltrated CD8+ and CD4+ T cells along with macrophages and natural killer cells was observed in tumor treated with combined treatment. Altogether, results presented in this study suggested the potential of ox-MWCNTs-mediated HT as an anticancer therapeutic agent, hence might be beneficial in the future of breast cancer treatment

Human papillomavirus type 16 oncoproteins as immune modulators and immune targets

Human papillomavirus (HPV) is the primary etiological agent of cervical cancer. The high-risk HPV16 is the most prevalent HPV genotype worldwide and its DNA is detectable in more than 50% of all cervical tumours. The consistent over-expression of the HPV E6 and E7 oncogenes is necessary for cervical carcinogenesis. High mortality and morbidity due to HPV-associated disease still remains a major health burden globally. Since the current virus-like particle vaccines exert no therapeutic efficacy, better therapeutic strategies are required for the treatment of pre-existing, potentially cancer-causing, HPV infections. The aims of this study were firstly to understand the immune-modulation by HPV16 E7 on antigen presentation in the epidermal microenvironment and secondly to explore the potential use of HPV16 E6 as a target for immunotherapeutic approach for HPV vaccine candidate. In HPV infection, Langerhans cells (LC) have been thought to be important in antigen uptake, presentation and consequently initiating the immune response. It was reported previously that the frequency of LC was greatly reduced in HPV16 infections. In this study, the effect of HPV16 E7 in modulating antigen presentation and its downstream effects on the CD8 T cell response was investigated. Replication-defective lentiviral vectors were used to deliver HPV16 E7, a luciferase reporter and the model antigen ovalbumin specifically to the epidermis. It was demonstrated that E7 is capable of reducing the density of LC in the transduced epidermis independent of any viral proteins. When the kinetics of the luciferase gene expression in the presence and absence of HPV16 E7 was monitored, it was observed that E7 delayed the loss of the luciferase expressing lentivirus transduced cells. We also showed that the magnitude of the CD8+ T cell response to skin-expressed ovalbumin was significantly reduced in E7 mice, compared with control mice. However, it was observed that the down-regulation effect occurred independent of LC since LC depletion did not alter the strength of CD8 T cell response in both E7 and control mice, suggesting E7 regulation of other skin-derived dendritic cells in antigen presentation and function. The therapeutic efficacy of E6-VLP (virus like particles) derived from Rabbit haemorrhagic disease virus against tumour cells expressing HPV16 E6 and E7 was tested in a murine cervical cancer model. It was shown that E6-RHDV-VLP was efficient in inducing an anti-tumour effect against TC-1 tumour cells. Moreover, the incorporation of a universal helper T cell epitope, PADRE into E6-VLP further improved the therapeutic effect and prolonged the median survival, compared to mice immunised with E6-VLP without PADRE. Furthermore, treatment either with anti-CTLA-4 antibody to block T cell suppression or with PC61 (anti-CD25) to deplete regulatory T cells has shown to enhance the vaccine potency afforded by E6-VLP-PADRE. Data presented here highlight the potential therapeutic use of E6 and/or E7 for the restoration of factors impeding the immune response as well as a target for immunotherapeutic approach against HPV-induced cervical cancer. The information gained from this research contributes to our understanding of HPV regulation of antigen presentation in the skin and may have implications for immunotherapy against HPV pre-cancers

Global Stability and Thermal Optimal Control Strategies for Hyperthermia Treatment of Malignant Tumors

Malignant tumor (cancer) is the leading cause of death globally and the annual cost of managing cancer is trillions of dollars. Although, there are established therapies including radiotherapy, chemotherapy and phototherapy for malignant tumors, the hypoxic environment of tumors and poor perfusion act as barriers to these therapies. Hyperthermia takes advantage of oxygen deficiency and irregular perfusion in the tumor environment to destroy malignant cells. Despite successes recorded with hyperthermia, there are concerns with the post-treatment condition of patients as well as the required thermal dose to prevent harm. The investigation of the dynamics of tumor-induced immune suppression with hyperthermia treatment using mathematical analysis and optimal control theory is potentially valuable in the development of hyperthermia treatment. The role of novel tumor-derived cytokines in counterattacking immune cells is considered in this study as a mechanism accounting for the aggressiveness of malignant tumors. Since biological processes are not instantaneous, a discrete time delay is used to model biological processes involved in tumor inhibitory mechanisms by secretion, the elaboration of suppressive cells, and effector cell differentiation to produce suppressive cells. Analytical results obtained using Lyapunov’s function indicate the conditions required for global stability of the tumor-present steady-state. A thermal optimal control strategy is pursued based on optimal control theory, and the best strategy to avoid adverse outcomes is obtained. We validate the analytical results numerically and demonstrate the impact of both inadequate and excessive heat on the dynamics of interactive cell functioning

Stability and sensitivity analysis of tumor-induceimmune suppression with time delay

Emerging biomedical evidences suggest that tumor has capacity not only to secrete immunesuppression but also attack effector cells. In this work, we present a delay model to study the dynamics of tumor, effector cells and TGF-β interaction with incorporation of tumor-derived macrophages for counterattack. The existence of stationary solutions of the model and their long time behaviors are obtained analytically. The analytical results reveal that tumor-free stationary solution is stable if the body cells do not proliferate excessively, and tumor-present stationary solution is asymptotically stable if the proliferation rate of effector cells is greater than its suppression by TGF-β otherwise is unstable. For an unstable scenario, we examine the sensitivity of model parameters to ascertain their role in tumor-immune escape. This effort indicates the reducing function for effector cells suppression and increasing functions for tumors elimination. The numerical results validate all the analytical results and reveal the optimum tumor elimination strategies with amplifying effect on effector cells performance

Antibacterial activity of silver nanoparticles synthesized from Persicaria odorata (L.) sojak leaves extract

Recent findings suggested that plant-mediated synthesized silver nanoparticles exhibit significant antibacterial property, yet the exact mechanisms and toxicity remain unraveled. Hence, this present study aims to utilize the leaves extract from Persicaria odorata (L.) Sojak as the reducing agent for the fabrication of silver nanoparticles (PO-AgNPs) and to evaluate their antibacterial properties. The formation of PO-AgNPs was verified by ultraviolet-visible (UV-Vis) spectrophotometer which revealed an absorption peak at around 440 nm. Further characterization using Fourier transform infrared (FTIR) spectroscopy, energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) analysis showed the presence of biomolecules from the leaves extract, which was responsible for the productions of PO-AgNPs and the crystalline nature of the PO-AgNPs. Field emission scanning electron microscope (FESEM) images revealed the spherical structure of PO-AgNPs. Disc diffusion and time-kill assay results showed that PO-AgNPs exhibited inhibition against tested Methicillin-resistant Staphylococcus aureus (MRSA), S. aureus, and S. epidermidis, and Pseudomonas aeruginosa. Overall, these results further consolidate that PO-AgNPs possess good antibacterial properties. The inhibition mechanisms of PO-AgNPs against those pathogenic bacteria will be investigated in future works, particularly to explain how PO-AgNPs caused toxicity in bacteria

Bionanotechnology: current progress in applied nanomaterials research

Bionanotechnology is a multidisciplinary fields involving nanotechnology for biological and medical applications. One of the area is applied nanomaterials such as biomaterial nanoparticles, adjuvant therapy for cancer, antibacterial agent and drug delivery system. Nanomaterials offer more advantages due to their smaller particles that exhibits higher performance and effectiveness of their application. In our recent progress of applied nanomaterials researches, several synthesized nanomaterials that we want to highlight are silica aerogels nanoparticles as biomaterial and zeolite NaY nanoparticles as adjuvant therapy for cancer. Both of them were synthesized from rice husk ash as silica source. We have found that the synthesized silica aerogels nanoparticles increased the viability and proliferation of normal human fibroblast cells in vitro as well as enhanced bioactivity in simulated body fluid after incorporated with hydroxyapatite. Thus, the hydroxyapatite incorporated silica aerogels nanoparticles could be used as a biomaterial or for wound healing. Whereas, the zeolite NaY nanoparticles had the ability to withstand gastrointestinal condition and good anticancer properties, making it a possible alternative adjuvant therapy for colorectal cancer. There are many researches can be performed in the area of bionanotechnology in the future such as biosynthesis of silver nanoparticles from plant (herbs) extract and synthesized zeolite nanoparticles from kaolin-clay loaded with silver ions as antibacterial agent. Research in the bionanotechnology field necessitate understanding and facilities of various disciplines including physical, analytical, inorganic and organic chemistry as well as biology and medical sciences, thus collaboration with various fields is encouraging to ensure the success of the research output