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Fulltext Role of microRNAs as biomarkers of cervical carcinogenesis: a systematic review

Nagandla K, Lin KH, Chitra E, Jamli MFBM

Obstet Gynecol Sci, 2021 Sep;64(5):419-436.
PMID: 34384196 DOI: 10.5468/ogs.21123

We performed a systematic review to identify the role of microRNAs (miRNAs) as biomarkers in the progression of cervical precancerous lesions. A comprehensive search of the Cochrane Controlled Register of Trials, PubMed, ScienceDirect, and Embase databases was performed for articles published between January 2010 and June 2020. The following Medical Subject Headings (MeSH) terms were searched: "microRNA" and "cervical" and "lesion." All study designs that aimed to evaluate the correlation of miRNA expression with different precancerous cervical staging and/or cervical cancer were included, except for case reports and case series. Approximately 82 individual miRNAs were found to be significant in differentiating the stages of cervical carcinogenesis. Among the miRNAs, miR-21 is the most prevalent, and it is consistently upregulated progressively from normal cervical to worsening cervical lesion stages in both cell and serum samples. miR-205 has been shown to have a higher specificity than human papilloma virus testing in predicting the absence of high-grade squamous intraepithelial lesions (HSILs) in exfoliated cell samples. The tumor suppressor miRNAs miR-34, let-7, miR-203 miR-29, and miR-375 were significantly downregulated in low-grade squamous intraepithelial lesions, HSILs, and cervical cancer. We found significant dysregulated miRNAs in cervical carcinogenesis with their dynamic expression changes and ability to detect viral persistency, risk prediction of low-grade lesions (cervical intraepithelial neoplasia [CIN] 2) to high-grade lesions (CIN 3), and progression of CIN 3 to cancer. Their ability to discriminate HSILs from non-dysplastic lesions has potential implications in early diagnosis and reducing overtreatment of otherwise regressive early preinvasive lesions.
Fulltext Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms

Ong TH, Chitra E, Ramamurthy S, Siddalingam RP, Yuen KH, Ambu SP, et al.

PLoS One, 2017;12(3):e0174888.
PMID: 28362873 DOI: 10.1371/journal.pone.0174888

Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.
Fulltext Cationic chitosan-propolis nanoparticles alter the zeta potential of S. epidermidis, inhibit biofilm formation by modulating gene expression and exhibit synergism with antibiotics

Ong TH, Chitra E, Ramamurthy S, Ling CCS, Ambu SP, Davamani F

PLoS One, 2019;14(2):e0213079.
PMID: 30818374 DOI: 10.1371/journal.pone.0213079

Staphylococcus epidermidis, is a common microflora of human body that can cause opportunistic infections associated with indwelling devices. It is resistant to multiple antibiotics necessitating the need for naturally occurring antibacterial agents. Malaysian propolis, a natural product obtained from beehives exhibits antimicrobial and antibiofilm properties. Chitosan-propolis nanoparticles (CPNP) were prepared using Malaysian propolis and tested for their effect against S. epidermidis. The cationic nanoparticles depicted a zeta potential of +40 and increased the net electric charge (zeta potential) of S. epidermidis from -17 to -11 mV in a concentration-dependent manner whereas, ethanol (Eth) and ethyl acetate (EA) extracts of propolis further decreased the zeta potential from -17 to -20 mV. Confocal laser scanning microscopy (CLSM) depicted that CPNP effectively disrupted biofilm formation by S. epidermidis and decreased viability to ~25% compared to Eth and EA with viability of ~60-70%. CPNP was more effective in reducing the viability of both planktonic as well as biofilm bacteria compared to Eth and EA. At 100 μg/mL concentration, CPNP decreased the survival of biofilm bacteria by ~70% compared to Eth or EA extracts which decreased viability by only 40%-50%. The morphology of bacterial biofilm examined by scanning electron microscopy depicted partial disruption of biofilm by Eth and EA extracts and significant disruption by CPNP reducing bacterial number in the biofilm by ~90%. Real time quantitative PCR analysis of gene expression in treated bacteria showed that genes involved in intercellular adhesion such as IcaABCD, embp and other related genes were significantly downregulated by CPNP. In addition to having a direct inhibitory effect on the survival of S. epidermidis, CPNP showed synergism with the antibiotics rifampicin, ciprofloxacin, vancomycin and doxycycline suggestive of effective treatment regimens. This would help decrease antibiotic treatment dose by at least 4-fold in combination therapies thereby opening up ways of tackling antibiotic resistance in bacteria.
Fulltext Root canal irrigants influence the hydrophobicity and adherence ofStaphylococcus epidermidisto root canal dentin: anin vitrostudy

Nagendrababu V, Sheriff Sultan O, Kannathasan S, Patel AS, Chitra E, Neelakantan P, et al.

Restor Dent Endod, 2018 Feb;43(1):e1.
PMID: 29487832 DOI: 10.5395/rde.2018.43.e1

Objectives: To determine the effect of root canal irrigants on the hydrophobicity and adherence ofStaphylococcus epidermidis(S. epidermidis) to root canal dentinin vitro.
Materials and Methods: Root dentin blocks (n= 60) were randomly divided into 4 groups based on the irrigation regimen: group 1, saline; group 2, 5.25% sodium hypochlorite (NaOCl); group 3, 5.25% NaOCl followed by 17% ethylenediaminetetraacetic acid (EDTA); group 4, same as group 3 followed by 2% chlorhexidine (CHX). The hydrophobicity ofS. epidermidisto root dentin was calculated by cell surface hydrophobicity while the adherence was observed by fluorescence microscopy, and bacteria were quantified using ImageJ software (National Institutes of Health). Statistical analysis of the data was done using Kruskal-Wallis test and Mann-WhitneyUtest (p= 0.05).
Results: The hydrophobicity and adherence ofS. epidermidisto dentin were significantly increased after irrigating with group 3 (NaOCl-EDTA) (p< 0.05), whereas in group 4 (NaOCl-EDTA-CHX) both hydrophobicity and adherence were significantly reduced (p< 0.05).
Conclusions: The adherence ofS. epidermidisto dentin was influenced differently by root canal irrigants. Final irrigation with CHX reduces the bacterial adherence and may impact biofilm formation.
Fulltext Depletion of regulatory T-cells leads to moderate B-cell antigenicity in respiratory syncytial virus infection

Shao HY, Huang JY, Lin YW, Yu SL, Chitra E, Chang CK, et al.

Int J Infect Dis, 2015 Dec;41:56-64.
PMID: 26555647 DOI: 10.1016/j.ijid.2015.10.026

The regulation of the immunopathology of respiratory syncytial virus (RSV) by regulatory T-cells (CD4(+)CD25(+)Foxp3(+); Tregs) is not understood.
Fulltext Inhibition of breast cancer xenografts in a mouse model and the induction of apoptosis in multiple breast cancer cell lines by lactoferricin B peptide

Rahman R, Fonseka AD, Sua SC, Ahmad M, Rajendran R, Ambu S, et al.

J Cell Mol Med, 2021 08;25(15):7181-7189.
PMID: 34236134 DOI: 10.1111/jcmm.16748

Breast cancer has a diverse aetiology characterized by the heterogeneous expression of hormone receptors and signalling molecules, resulting in varied sensitivity to chemotherapy. The adverse side effects of chemotherapy coupled with the development of drug resistance have prompted the exploration of natural products to combat cancer. Lactoferricin B (LfcinB) is a natural peptide derived from bovine lactoferrin that exhibits anticancer properties. LfcinB was evaluated in vitro for its inhibitory effects on cell lines representing different categories of breast cancer and in vivo for its suppressive effects on tumour xenografts in NOD-SCID mice. The different breast cancer cell lines exhibited varied levels of sensitivity to apoptosis induced by LfcinB in the order of SKBR3>MDA-MB-231>MDA-MB-468>MCF7, while the normal breast epithelial cells MCF-10A were not sensitive to LfcinB. The peptide also inhibited the invasion of the MDA-MB-231 and MDA-MB-468 cell lines. In the mouse xenograft model, intratumoural injections of LfcinB significantly reduced tumour growth rate and tumour size, as depicted by live imaging of the mice using in vivo imaging systems (IVIS). Harvested tumour volume and weight were significantly reduced by LfcinB treatment. LfcinB, therefore, is a promising and safe candidate that can be considered for the treatment of breast cancer.
Effect of madecassoside in reducing oxidative stress and blood glucose in streptozotocin-nicotinamide-induced diabetes in rats

Tan SC, Rajendran R, Bhattamisra SK, Krishnappa P, Davamani F, Chitra E, et al.

J Pharm Pharmacol, 2023 Aug 01;75(8):1034-1045.
PMID: 37402616 DOI: 10.1093/jpp/rgad063

OBJECTIVES: Madecassoside (MAD) is a triterpenoid constituent of Centella asiatica (L.) Urb., an ethnomedical tropical plant, extracts of which were shown to reduce blood glucose in experimental diabetes. This study examines MAD for its anti-hyperglycaemic effects and tests the hypothesis that it reduces the blood glucose in experimentally induced diabetic rats by protecting the β-cells.
METHODS: Diabetes was induced using streptozotocin (60 mg/kg, i.v.) followed by nicotinamide (210 mg/kg, intraperitoneal (i.p.)). MAD (50 mg/kg) was administered orally for 4 weeks, commencing 15 days after induction of diabetes; resveratrol (10 mg/kg) was used as a positive control. Fasting blood glucose, plasma insulin, HbA1c, liver and lipid parameters were measured, along with antioxidant enzymes and malondialdehyde as an index of lipid peroxidation; histological and immunohistochemical studies were also undertaken.
KEY FINDINGS: MAD normalized the elevated fasting blood glucose levels. This was associated with increased plasma insulin concentrations. MAD alleviated oxidative stress by improving enzymatic antioxidants and reducing lipid peroxidation. Histopathological examination showed significant recovery of islet structural degeneration and an increased area of islets. Immunohistochemical staining showed increased insulin content in islets of MAD-treated rats.
CONCLUSIONS: The results demonstrate an antidiabetic effect of MAD associated with preservation of β-cell structure and function.
Enantiomeric pairs of ternary copper(ii) complexes and their aldol-type condensation products: synthesis, characterization, and anticancer and epigenetic properties

Lee KY, Ng YL, Wang WS, Ng PY, Chan CW, Lai JW, et al.

Dalton Trans, 2019 Apr 09;48(15):4987-4999.
PMID: 30916098 DOI: 10.1039/c9dt00506d

Chiral enantiomers [Cu(phen)(l-ser)(H2O)]NO31 and [Cu(phen)(d-ser)(H2O)]NO32 (ser = serinato) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(ii) complexes, viz. l- and d-[Cu(phen)(OCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; OCA = oxazolidine-4-carboxylate; x = 1/2, 0-2) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography. The crystal structures of 1 and 3 showed both the cationic complexes to have a square pyramidal geometry. These complexes were about nine fold more potent than cisplatin against metastatic MDA-MB-231 breast cancer cells, inducing apoptotic cell death via ROS generation and a massive drop in mitochondrial membrane potential. The results of monitoring EZH1, EZH2 and H3K27me3 revealed that the mode of action of 1-4 also involved the downregulation of EZH2 and it seemed to be independent of the H3K27me3 status.