Mok Pooi Ling

Magneto-chemotherapy for cervical cancer treatment with camptothecin loaded Fe3O4 functionalized β-cyclodextrin nanovehicle

We portray a novel way to deal with the synthesis of iron oxide magnetic nanoparticle incorporated β-cyclodextrin (β-CD) nanocarrier stabilized by ethylenediamine tetra acetic acid (EDTA), which obtained remarkable biocompatibility and biodegradability. The functionality, crystalline nature, morphology and thermal decomposition nature of Fe3O4, β-CD–EDTA–Fe3O4 and β-CD–EDTA–Fe3O4/CPT nanocarriers were confirmed by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The mechanistic action of camptothecin (CPT) on cancer cells was studies relying to incorporation with the topoisomerase (topo I) and DNA complex formation. This prevented DNA re-ligation, causing DNA damage which resulted in apoptosis in cervical cancer (HeLa) cells. We noticed a higher number of cells arrested in the G1 phase with a decreasing cell count in the S phase and the G2/M phase at a lower concentration of β-CD–EDTA–Fe3O4/CPT. Consequently, via conjugation with Fe magnetic nanoparticles (MNPs), the molecular recognition between β-CD and target the cancerous cells make this nanovehicle a promising candidate for the non-invasive treatment of HeLa cells.

Impact of dengue virus (serotype DENV-2) infection on liver of BALB/c mice: A histopathological analysis

In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces. There were marked increases in the infiltration of mononuclear cells. The areas of hemorrhage and micro- and macrovesicular steatosis were noted. Necrosis and apoptosis were abundantly present. The hallmark of viral infection, i.e., cytopathic effects, included intracellular edema and vacuole formation, cumulatively led to sinusoidal and lobular collapse in the liver. The histopathological studies on autopsy specimens of fatal human DENV cases are important to shed light on tissue damage for preventive and treatment modalities, in order to manage future DENV infections. In this framework, the method present here on BALB/c mouse model may be used to study not only the effects of infections by other DENV serotypes, but also to investigate the effects of novel drugs, such as recently developed nano-formulations, and the relative recovery ability with intact immune functions of host.

Micro-anatomical changes in major blood vessel caused by dengue virus (serotype 2) infection

Dengue virus (DENV) has emerged as a major economic concern in developing countries, with 2.5 billion people believed to be at risk. Vascular endothelial cells (ECs) lining the circulatory system from heart to end vessels perform crucial functions in the human body, by aiding gas exchange in lungs, gaseous, nutritional and its waste exchange in all tissues, including the blood brain barrier, filtration of fluid in the glomeruli, neutrophil recruitment, hormone trafficking, as well as maintenance of blood vessel tone and hemostasis. These functions can be deregulated during DENV infection. In this study, BALB/c mice infected with DENV serotype 2 were analyzed histologically for changes in major blood vessels in response to DENV infection. In the uninfected mouse model, blood vessels showed normal architecture with intact endothelial monolayer, tunica media, and tunica adventitia. In the infected mouse model, DENV distorted the endothelium lining and disturbed the smooth muscle, elastic laminae and their supporting tissues causing vascular structural disarrangement. This may explain the severe pathological illness in DENV-infected individuals. The overall DENV-induced damages on the endothelial and its supporting tissues and the dysregulated immune reactions initiated by the host were discussed.

Fruit-derived Polysaccharides and Terpenoids: Recent Update on the Gastroprotective Effects and Mechanisms

Ulceration in the stomach develops in peptic ulcer disease when there is a loss of protective mucosal layers, particularly in Helicobacter pylori infection. Antibiotic therapy has failed to eradicate and impede the colonization of H. pylori. Despite given treatment, recurrent bleeding can occur and lead to death in the affected individual. The disease progression is also related to the non-steroidal inflammatory drug and stress. There are extensive research efforts to identify the gastroprotective property from various alkaloids, flavonoids, and tannins compounds from plants and marine. These natural products are believed to be safe for consumption. However, not much attention was given to summarize the carbohydrate and terpenoidal anti-ulcer compounds. Hence, this review will cover the possible mechanisms and information about acidic hydroxylans, arabinogalactan and rhamnogalacturon; and limonene, pinene, lupeol, citral, ursolic acid and nomilin to exemplify on the gastroprotective properties of polysaccharides and terpenoid, respectively, obtained from fruits. These compounds could act as a prebiotic to prevent the inhabitation of H. pylori, modulate the inflammation, suppress gastric cancer growth, and capable of stimulating the reparative mechanisms on the affected regions. Finally, this review provides the future research prospects of these natural compounds in an effort to develop new therapy for gastrointestinal tissue healing.

Morphological and genetical changes of endothelial progenitor cells after in-vitro conversion into photoreceptors

BACKGROUND Retinal degeneration is a condition ensued by various ocular disorders such as artery occlusion, diabetic retinopathy, retrolental fibroplasia and retinitis pigmentosa which cause abnormal loss of photoreceptor cells and lead to eventual vision impairment. No efficient treatment has yet been found, however, the use of stem cell therapy such as bone marrow and embryonic stem cells has opened a new treatment modality for retinal degenerative diseases. The major goal of this study is to analyze the potential of endothelial progenitor cells derived from bone marrow to differentiate into retinal neural cells for regenerative medicine purposes. METHODS In this study, endothelial progenitor cells were induced in-vitro with photoreceptor growth factor (taurine) for 21 days. Subsequently, the morphology and gene expression of CRX and RHO of the photoreceptors-induced EPCs were examined through immunostaining assay. FINDINGS The results indicated that the induced endothelial progenitor cells demonstrated positive gene expression of CRX and RHO. Our findings suggested that EPC cells may have a high advantage in cell replacement therapy for treating eye disease, in addition to other neural diseases, and may be a suitable cell source in regenerative medicine for eye disorders.

Indole alkaloids and anti-nociceptive mechanisms of Tabernaemontana divaricata (L.) R. Br. flower methanolic extract

Flowers of Tabernaemontana divaricata (L.) R. Br., (Apocynaceae) are used in traditional medicine for analgesic property. The present study was performed to isolate the active principles and investigate the mechanisms involved in the anti-nociception caused by T. divaricata flower methanolic extract (TDFME). The extract in the doses of 125, 250 and 500 mg/kg, p.o was subjected to various assays in acetic acid induced abdominal writhing and formalin induced paw licking test models. Naloxone, L-Arginine, Glibenclamide and Glutamate were used as inducers while Morphine, L-NAME, Methylene blue and Aspirin served as standard drugs. The phytochemical analysis led to the isolation of three indole alkaloids namely Voacangine, Catharanthine and O-acetyl Vallesamine. The anti-nociception produced by TDFME was attenuated significantly (p< 0.001) by the intra-peritoneal pretreatment of naloxone, L-Arginine and glibenclamide. The nociception produced by glutamate was inhibited by TDFME. TDFME also enhanced the antinociceptive activity of L-NAME when given in combination. However TDFME co-administration did not produce significant results with methylene blue indicating lack of cGMP involvement. These results indicate that TDFME produces anti-nociception action mediated by opioid, nitric oxide, K+-ATP and glutamate mechanisms and the effect is largely related to the indole alkaloids.

3D modelling of the pathogenic Leptospira protein LipL32: A bioinformatics approach

Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira species (Leptospiraceae). LipL32 is an abundant lipoprotein from the outer membrane proteins (OMPs) group, highly conserved among pathogenic and intermediate Leptospira species. Several studies used LipL32 as a specific gene to identify the presence of leptospires. This research was aimed to study the characteristics of LipL32 protein gene code, to fill the knowledge gap concerning the most appropriate gene that can be used as antigen to detect the Leptospira. Here, we investigated the features of LipL32 in fourteen Leptospira pathogenic strains based on comparative analyses of their primary, secondary structures and 3D modeling using a bioinformatics approach. Furthermore, the physicochemical properties of LipL32 in different strains were studied, shedding light on the identity of signal peptides, as well as on the secondary and tertiary structure of the LipL32 protein, supported by 3D modelling assays. The results showed that the LipL32 gene was present in all the fourteen pathogenic Leptospira strains used in this study, with limited diversity in terms of sequence conservation, hydrophobic group, hydrophilic group and number of turns (random coil). Overall, these results add basic knowledge to the characteristics of LipL32 protein, contributing to the identification of potential antigen candidates in future research, in order to ensure prompt and reliable detection of pathogenic Leptospira species.