Adi Idris

Interleukin 1β—A Potential Salivary Biomarker for Cancer Progression?

The relationship between cancer and inflammation is a complex but intimate one. Decades of work has shown to us that cancer progression is influenced by a multitude of factors, including genetic, environmental, and immunological factors. We often overlook that cancer progression is also a pathological consequence of a dysregulated inflammatory control in the body. A current emerging topic in cancer research is the role of inflammasomes in carcinogenesis. The inflammasome is a multicomplex protein platform that when activated results in the release of proinflammatory cytokines, such as interleukin (IL)-1β. There is increasing evidence suggesting that IL-1β plays a pivotal role in cancer progression. This short review proposes the possibility of using IL-1β as a potential cancer progression biomarker and discusses the use of saliva as a model biological fluid for measuring physiological IL-1β levels in the body.

Medicinal Plants: A Potential Source of Compounds for Targeting Cell Division

Modern medicinal plant drug discovery has provided pharmacologically active compounds targeted against a multitude of conditions and diseases, such as infection, inflammation, and cancer. To date, natural products from medicinal plants remain a solid niche as a source from which cancer therapies can be derived. Among other properties, one favorable characteristic of an anticancer drug is its ability to block the uncontrollable process of cell division, as cancer cells are notorious for their abnormal cell division. There are numerous other documented works on the potential anticancer activity of drugs derived from medicinal plants, and their effects on cell division are an attractive and growing therapeutic target. Despite this, there remains a vast number of unidentified natural products that are potentially promising sources for medical applications. This mini review aims to revise the current knowledge of the effects of natural plant products on cell division.

Parasitic Mistletoes of the Genera Scurrula and Viscum: From Bench to Bedside

The mistletoes, stem hemiparasites of Asia and Europe, have been used as medicinal herbs for many years and possess sophisticated systems to obtain nutrients from their host plants. Although knowledge about ethnomedicinal uses of mistletoes is prevalent in Asia, systematic scientific study of these plants is still lacking, unlike its European counterparts. This review aims to evaluate the literature on Scurrula and Viscum mistletoes. Both mistletoes were found to have anticancer, antimicrobial, antioxidant and antihypertensive properties. Plants from the genus Scurrula were found to inhibit cancer growth due to presence of phytoconstituents such as quercetin and fatty acid chains. Similar to plants from the genus Viscum, Scurrula also possesses TNFα activity to strengthen the immune system to combat cancer. In line with its anticancer activity, both mistletoes are rich in antioxidants that confer protection against cancer as well as neurodegeneration. Extracts from plants of both genera showed evidence of vasodilation and thus, antihypertensive effects. Other therapeutic effects such as weight loss, postpartum and gastrointestinal healing from different plants of the genus Scurrula are documented. As the therapeutic effects of plants from Scurrula are still in exploration stage, there is currently no known clinical trial on these plants. However, there are few on-going clinical trials for Viscum album that demonstrate the functionalities of these mistletoes. Future work required for exploring the benefits of these plants and ways to develop both parasitic plants as a source of pharmacological drug are explained in this article.

Mesoporous silica nanoparticles as a carrier platform for intracellular delivery of nucleic acids

Virus-mediated gene delivery has been, to date, the most successful and efficient method for gene therapy. However, this method has been challenged because of serious safety concerns. Over the past decade, mesoporous silica nanoparticles (MSNs) have attracted much attention for intracellular delivery of nucleic acids. Delivery of cellular plasmid DNA (pDNA) is designed to replace the function of a defective gene and restore its normal function in the cell. Delivery of small interfering RNAs (siRNAs) can selectively knockdown genes by targeting specific mRNAs. The biocompatibility and unique structures of MSNs make these nanoparticles ideal candidates to act as biomolecule carriers. This concise review highlights current progress in the field of nucleic acid delivery using MSNs, specifically for delivery of pDNA, siRNA, and combinatorial delivery of nucleic acids and drugs. The review describes important design parameters presently being applied to MSNs to administer drugs and therapeutic nucleic acids.

Human diseases, immunity and the oral microbiota—Insights gained from metagenomic studies

Abstract The immune system consists of a complex but organised myriad of cell types that continually maintain and survey their resident environment. It is this balanced homeostatic relationship between the cells of the immune system and its surrounding environment that shapes the microbial flora. In the oral cavity, the immune system not only has to harmonise with the ecology of commensal bacteria, fungi and viruses but also should be able to defend against pathogenic microbes. In fact, the oral microbiota is altered in situations when the immune system is dysregulated. There are a number of human diseases or conditions that perturb the balance of the host immune system and have an effect on the host oral microbiota. If this balance is disturbed, the symbiotic relationship will shift to allow the colonisation or overgrowth of potentially pathogenic species, inducing a pathogenic process that leads to various disease symptoms. The dynamics balance between the immune status and the oral microbial community of an individual has remained understudied till recently. Advances in metagenomics allow detailed investigations into oral microbial population and the possible diversity. This concise review summarises the current findings using metagenomic approaches for studying oral microbial flora diversity.

The diurnal pattern of salivary IL-1β in healthy young adults

Abstract Disruption in circadian rhythm affects the production of inflammatory cytokines. Understanding how it behaves in diseased conditions is essential. Despite the role of the interleukin-1β (IL-1β), a potent inflammatory cytokine, in human diseases, little is known about the steady-state circadian rhythm of IL-1β in healthy individuals. This short study investigates the diurnal pattern of salivary IL-1β throughout the day in healthy young adults. Twelve participants provided saliva samples at various times throughout the day. Salivary IL-1β were assessed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Salivary IL-1β levels were highest at 0430 h and lowest at 0000 h and shared a similar diurnal pattern to that of salivary IL-6. Western blot analysis showed that these levels correspond to the mature form of IL-1β. Our findings are important as it established the diurnal pattern of salivary IL-1β is fluctuating normally throughout the day. The findings also open an incredible opportunity for developing research conducted in the field with saliva as the diagnostic tool.

Salivary testosterone as a potential indicator for risky behaviour associated with smoking-related peer pressure in adolescents.

Abstract Early smoking is considered an indicator for risky behaviour in adolescents. Although social indicators predicting adolescent smoking are known, biological indicators have not been defined. This study aimed to establish whether salivary testosterone could be used as a “predictive biomarker” for smoking-associated peer pressure. Saliva samples were collected from Bruneian adolescents (aged 13–17 years) by the passive drool method. Salivary testosterone concentration was determined by enzyme-linked immunosorbent assay. Salivary testosterone concentration and smoking-associated peer pressure indicators were compared between adolescent males and females and statistical significance was determined by an independent samples t-test. A significant positive relationship between smoking-associated peer pressure and salivary testosterone levels in adolescents was found. However, this relationship was not significant when males and females were considered separately. Our data suggest that students who have tried cigarette smoking and have friends who are cigarette smokers have higher salivary testosterone levels.

Cellular Responses to Cytosolic Double-stranded RNA—The Role of the Inflammasome

Sensing the presence of a pathogen is an evolutionarily ancient trait, especially for cells of the innate immune system. The innate immune response against pathogens, such as viruses, begins with recognition of pathogen-associated molecular patterns (PAMPs) by specific pattern-recognition receptors (PRRs). Cytosolic double-stranded RNA (dsRNA) is emerging as a critical PAMP in the detection of viral infections. This recognition results in the production of antiviral and proinflammatory cytokines and, often, the death of the virus-infected cell. This review focuses on the current developments in the role of inflammasomes in response to the presence of cytosolic dsRNA in host cells. More importantly, it highlights important unanswered questions that if addressed will help us better understand the ways in which host cells respond to viral infection, in particular RNA viruses.

Melastoma malabathricum ethyl acetate fraction induces secondary necrosis in human breast and lung cancer cell lines

Background: Melastoma malabathricum (MM) is a traditional plant used in the Borneo region. The cytotoxic effects of methanol extracts from MM leaves have been reported in a number of human cancer cell lines. However, the mode of cell death by MM has not been investigated. Objective: We investigated the cytotoxic effects of MM in both human breast and lung cancer cell lines, MCF-7 and A549, respectively, and defined the mode of cell death. Materials and Methods: Cell viability was measured using the 3-(4-, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Annexin-V/propidium iodide (PI) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was done to determine the mode of cell death. Results: The MTT assay revealed that MM extract had an IC50 of >400 μ g/ml on both cell lines at 24 h posttreatment. Flow cytometric and fluorescence microscopy analysis of Annexin-V/PI stained MM-treated cells revealed that the majority of the cells underwent secondary necrosis/late apoptosis. TUNEL assay showed that little to no DNA nicks were present in MM-treated cells, suggesting that cells have undergone secondary necrosis, not late apoptosis, at that time point. Conclusion: MCF-7 and A549 cells undergoes secondary necrosis 24 h post-treatment with MM extract. MM leaf extract could be a potential source for a novel anti-tumor agent for cancer therapy. Abbreviations used: DMSO: Dimethyl sulfoxide; MM: Melastoma malabathricum; MTT: 3-(4-, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; PI: Propidium iodide; TUNEL: Terminal deoxynucleotidyl transferase dUTP nick-end labeling.

Interaction and cellular uptake of surface-modified carbon dot nanoparticles by J774.1 macrophages

Carbon dot (Cdot) nanoparticles are an emerging class of carbon nanomaterials with a promising potential for drug delivery and bio imaging applications. Although the interaction between Cdots and non-immune cell types has been well studied, Cdot interactions with macrophages have not been investigated. Exposure of Cdot nanoparticles to J774.1 cells, a murine macrophage cell line, resulted in minimal toxicity, where notable toxicity was only seen with Cdot concentrations higher than 0.5 mg/ml. Flow cytometric analysis revealed that Cdots prepared from citric acid were internalized at significantly higher levels by macrophages compared with those prepared from bamboo leaves. Interestingly, macrophages preferentially took up phenylboronic acid (PB)-modified nanoparticles. By fluorescence microscopy, strong blue light-specific punctate Cdot fluorescence resembling Cdot structures in the cytosolic space was mostly observed in J774.1 macrophages exposed to PB-modified nanoparticles and not unmodified Cdot nanoparticles. PB binds to sialic acid residues that are overexpressed on diseased cell surfaces. Our findings demonstrate that PB-conjugated Cdots can be taken up by macrophages with low toxicity and high efficiency. These modified Cdots can be used to deliver drugs to suppress or eliminate aberrant immune cells such as macrophages associated with tumors such as tumor-associated macrophages.