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Fulltext Oral Hypoglycemic Agents in pregnancy: An Update

Kavitha N, De S, Kanagasabai S

J Obstet Gynaecol India, 2013 Apr;63(2):82-7.
PMID: 24431611 DOI: 10.1007/s13224-012-0312-z

INTRODUCTION: Traditionally, insulin has been the gold standard in the management of Type 2 diabetes in pregnancy and gestational diabetes. However, insulin therapy can be inconvenient because of the needs for multiple injections, its associated cost, pain at the injection site, need for refrigeration, and skillful handling of the syringes. This has led to the exploration of oral hypoglycemic agents as an alternative to insulin therapy.
OBJECTIVES: This review examines and evaluates the evidences on the efficacy, safety, and current recommendations of oral hypoglycemic agents.
CONCLUSION: The evidence of this study supports the use of glyburide and metformin in the management of Type 2 diabetes and gestational diabetes with no increased risk of neonatal hypoglycemia or congenital anomalies. The safety of these oral hypoglycemic agents are limited to the prenatal period and more randomized controlled trials are required to provide information on the long-term follow up on neonatal and cognitive development.
Dihydroorotate dehydrogenase (DHODH) inhibitors affect ATP depletion, endogenous ROS and mediate S-phase arrest in breast cancer cells

Mohamad Fairus AK, Choudhary B, Hosahalli S, Kavitha N, Shatrah O

Biochimie, 2017 Apr;135:154-163.
PMID: 28196676 DOI: 10.1016/j.biochi.2017.02.003

Dihydroorotate dehydrogenase (DHODH) is the key enzyme in de novo biosynthesis of pyrimidine in both prokaryotes and eukaryotes. The de novo pathway of pyrimidine biosynthesis is essential in cancer cells proliferation. Leflunomide is an approved DHODH inhibitor that has been widely used for the treatment of arthritis. Similarly, brequinar sodium is another DHODH inhibitor that showed anti-tumour effect in MC38 colon carcinoma cells when used in combination with fluorouracil. Despite the potential role of DHODH inhibitors in cancer therapy, their mechanisms of action remain obscure and await further elucidation. Here, we evaluated the effect of DHODH inhibitors on the production of ATP and ROS in sensitive and non-sensitive breast cancer cells. Subsequently, the effects of DHODH inhibitors on cell cycle as well as on signalling molecules such as p53, p65 and STAT6 were evaluated in sensitive T-47D and non-sensitive MDAMB-436 cells. The correlations between DHODH protein expression, proliferation speed and sensitivity to DHODH inhibitors were also investigated in a panel of cancer cell lines. DHODH inhibitors-sensitive T-47D and MDAMB-231 cells appeared to preserve ROS production closely to endogenous ROS level whereas the opposite was observed in non-sensitive MDAMB-436 and W3.006 cells. In addition, we observed approximately 90% of intracellular ATP depletion in highly sensitive T-47D and MDAMB-231 cells compared to non-sensitive MDAMB-436 cells. There was significant over-expression of p53, p65 and STAT6 signalling molecules in sensitive cells which may be involved in mediating the S-phase arrest in cell cycle progression. The current study suggests that DHODH inhibitors are most effective in cells that express high levels of DHODH enzyme. The inhibition of cell proliferation by these inhibitors appears to be accompanied by ROS production as well as ATP depletion. The increase in expression of signalling molecules observed may be due to pyrimidine depletion which subsequently leads to cell cycle arrest at S-phase.
Fulltext Real time anti-Toxoplasma gondii activity of an active fraction of Eurycoma longifolia root studied by in situ scanning and transmission electron microscopy

Kavitha N, Noordin R, Kit-Lam C, Sasidharan S

Molecules, 2012 Aug 02;17(8):9207-19.
PMID: 22858841 DOI: 10.3390/molecules17089207

The inhibitory effect of active fractions of Eurycoma longifolia (E. longifolia) root, namely TAF355 and TAF401, were evaluated against Toxoplasma gondii (T. gondii). In our previous study, we demonstrated that T. gondii was susceptible to TAF355 and TAF401 with IC₅₀ values of 1.125 µg/mL and 1.375 µg/mL, respectively. Transmission (TEM) and scanning electron microscopy (SEM) observations were used to study the in situ antiparasitic activity at the IC₅₀ value. Clindamycin was used as positive control. SEM examination revealed cell wall alterations with formation of invaginations followed by completely collapsed cells compared to the normal T. gondii cells in response to the fractions. The main abnormality noted via TEM study was decreased cytoplasmic volume, leaving a state of structural disorganization within the cell cytoplasm and destruction of its organelles as early as 12 h of treatment, which indicated of rapid antiparasitic activity of the E. longifolia fractions. The significant antiparasitic activity shown by the TAF355 and TAF401 active fractions of E. longifolia suggests their potential as new anti-T. gondii agent candidates.
Fulltext In vitro anti-Toxoplasma gondii activity of root extract/fractions of Eurycoma longifolia Jack

Kavitha N, Noordin R, Chan KL, Sasidharan S

BMC Complement Altern Med, 2012;12:91.
PMID: 22781137 DOI: 10.1186/1472-6882-12-91

Toxoplasma gondii infection causes toxoplasmosis, an infectious disease with worldwide prevalence. The limited efficiency of drugs against this infection, their side effects and the potential appearance of resistant strains make the search of novel drugs an essential need. We examined Eurycoma longifolia root extract and fractions as potential sources of new compounds with high activity and low toxicity. The main goal of this study was to investigate the anti-T. gondii activity of crude extract (TACME) and four fractions (TAF 273, TAF 355, TAF 191 and TAF 401) from E. longifolia, with clindamycin as the positive control.
Deactivation of Telomerase Enzyme and Telomere Destabilization by Natural Products: a Potential Target for Cancer Green Therapy

Sasidharan S, Jothy SL, Kavitha N, Chen Y, Kanwar JR

Asian Pac J Cancer Prev, 2015;16(18):8671.
PMID: 26745135
Phaleria macrocarpa (Boerl.) fruit induce G0/G1 and G2/M cell cycle arrest and apoptosis through mitochondria-mediated pathway in MDA-MB-231 human breast cancer cell

Kavitha N, Ein Oon C, Chen Y, Kanwar JR, Sasidharan S

J Ethnopharmacol, 2017 Apr 06;201:42-55.
PMID: 28263848 DOI: 10.1016/j.jep.2017.02.041

ETHNOPHARMACOLOGICAL RELEVANCE: Phaleria macrocarpa (Scheff) Boerl, is a well-known folk medicinal plant in Indonesia. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and hearth disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases.
AIM OF THE STUDY: The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death.
MATERIALS AND METHODS: MDA-MB-231 cells were incubated with PMEAF for 24h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array.
RESULTS: The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G0/G1 and G2/M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆Ψm) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c, p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells.
CONCLUSION: The results indicated that PMEAF treatment induced apoptosis in MDA-MB-231 cells through intrinsic mitochondrial related pathway with the participation of pro and anti-apoptotic proteins, caspases, G0/G1 and G2/M-phases cell cycle arrest by p53-mediated mechanism.
In situ morphological assessment of apoptosis induced by Phaleria macrocarpa (Boerl.) fruit ethyl acetate fraction (PMEAF) in MDA-MB-231 cells by microscopy observation

Kavitha N, Chen Y, Kanwar JR, Sasidharan S

Biomed Pharmacother, 2017 Mar;87:609-620.
PMID: 28081471 DOI: 10.1016/j.biopha.2016.12.127

Phaleria macrocarpa (Boerl.) is a well-known medicinal plant and have been extensively used as traditional medicine for ages in treatment of various diseases. The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) by using various conventional and modern microscopy techniques. The cytotoxicity of PMEAF treated MDA-MB-231 cells was determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and CyQuant Cell Proliferation Assay after 24h of treatment. Both results were indicated that the PMEAF is a potential anticancer agent with the average IC50 values of 18.10μg/mL by inhibiting the MDA-MB-231 cell proliferation. Various conventional and modern microscopy techniques such as light microscopy, holographic microscopy, transmission (TEM) and scanning (SEM) electron microscope were used for the observation of morphological changes in PMEAF treated MDA-MB-231cells for 24h. The characteristic of apoptotic cell death includes cell shrinkage, membrane blebs, chromatin condensation and the formation of apoptotic bodies were observed. PMEAF might be the best candidate for developing more potent anticancer drugs or chemo-preventive supplements.
MicroRNAs: biogenesis, roles for carcinogenesis and as potential biomarkers for cancer diagnosis and prognosis

Kavitha N, Vijayarathna S, Jothy SL, Oon CE, Chen Y, Kanwar JR, et al.

Asian Pac J Cancer Prev, 2014;15(18):7489-97.
PMID: 25292018

MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.
MicroRNA profiling in MDA-MB-231 human breast cancer cell exposed to the Phaleria macrocarpa (Boerl.) fruit ethyl acetate fraction (PMEAF) through IIlumina Hi-Seq technologies and various in silico bioinformatics tools

Kavitha N, Vijayarathna S, Shanmugapriya, Oon CE, Chen Y, Kanwar JR, et al.

J Ethnopharmacol, 2018 Mar 01;213:118-131.
PMID: 29154802 DOI: 10.1016/j.jep.2017.11.009

ETHNOPHARMACOLOGICAL RELEVANCE: Phaleria macrocarpa (Scheff) Boerl, is a famous traditional medicinal plant which exhibited cytotoxicity against various cancerous cells. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and heart disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases.
AIM OF THE STUDY: Recent studies have demonstrated a potent anticancer potential of P. macrocarpa, especially against HeLa cell. The objective of this study was to investigate the regulation of miRNAs on MDA-MB-231 treated with P. macrocarpa ethyl acetate fraction (PMEAF).
MATERIALS AND METHODS: The regulation of miRNAs on MDA-MB-231 cells treated with PMEAF was studied through IIlumina, Hi-Seq. 2000 platform of Next Generation Sequencing (NGS) and various in silico bioinformatics tools.
RESULTS: The PMEAF treatment against MDA-MB-231 cells identified 10 upregulated and 10 downregulated miRNAs. A set of 606 target genes of 10 upregulated miRNAs and 517 target genes of 10 downregulated miRNAs were predicted based on computational and validated databases by using miRGate DB Query. Meanwhile, results from DAVID Bioinformatics Resources 6.8 specified the functional annotation of the upregulated miRNAs involvement in cancer pathway by suppressing the oncogenes and downregulating miRNAs by expressing the tumour suppressor genes in the regulation of apoptosis pathway.
CONCLUSION: In conclusion, the results of this study proved that PMEAF is a promising anticancer agent with high cytotoxicity against MDA-MB-231 breast cancer cells and it induced apoptotic cell death mechanism through the regulation of miRNAs. PMEAF might be the best candidate for developing more potent anticancer drugs or chemo preventive supplements.
Fulltext Validation of the Short Version (TLS-15) of the Triangular Love Scale (TLS-45) across 37 Languages

Kowal M, Sorokowski P, Dinić BM, Pisanski K, Gjoneska B, Frederick DA, et al.

Arch Sex Behav, 2024 Feb;53(2):839-857.
PMID: 37884798 DOI: 10.1007/s10508-023-02702-7

Love is a phenomenon that occurs across the world and affects many aspects of human life, including the choice of, and process of bonding with, a romantic partner. Thus, developing a reliable and valid measure of love experiences is crucial. One of the most popular tools to quantify love is Sternberg's 45-item Triangular Love Scale (TLS-45), which measures three love components: intimacy, passion, and commitment. However, our literature review reveals that most studies (64%) use a broad variety of shortened versions of the TLS-45. Here, aiming to achieve scientific consensus and improve the reliability, comparability, and generalizability of results across studies, we developed a short version of the scale-the TLS-15-comprised of 15 items with 5-point, rather than 9-point, response scales. In Study 1 (N = 7,332), we re-analyzed secondary data from a large-scale multinational study that validated the original TLS-45 to establish whether the scale could be truncated. In Study 2 (N = 307), we provided evidence for the three-factor structure of the TLS-15 and its reliability. Study 3 (N = 413) confirmed convergent validity and test-retest stability of the TLS-15. Study 4 (N = 60,311) presented a large-scale validation across 37 linguistic versions of the TLS-15 on a cross-cultural sample spanning every continent of the globe. The overall results provide support for the reliability, validity, and cross-cultural invariance of the TLS-15, which can be used as a measure of love components-either separately or jointly as a three-factor measure.
Correction to: Validation of the Short Version (TLS-15) of the Triangular Love Scale (TLS-45) Across 37 Languages

Kowal M, Sorokowski P, Dinić BM, Pisanski K, Gjoneska B, Frederick DA, et al.

Arch Sex Behav, 2024 Feb;53(2):859-861.
PMID: 38038856 DOI: 10.1007/s10508-023-02751-y