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  1. Kunnath AP, Priyashini T
    Cureus, 2019 Jun 16;11(6):e4907.
    PMID: 31423385 DOI: 10.7759/cureus.4907
    Cancer is one of the greatest threats posed to society, necessitating appropriate diagnosis methods. Modern targeted therapies have greatly advanced the treatment of several solid tumors. The rational use of these agents requires optimal strategies for the rapid and accurate detection of targetable genomic alterations at the time of initial diagnosis and when acquired resistance to targeted therapies develops. Currently used techniques, such as tissue genotyping, have limitations such as difficulty in categorizing tumors, needing frequent sampling, and difficulty in obtaining samples. To overcome these issues, cost-effective and non-invasive methods are an urgent requisite, which would provide an insight into the real-time dynamics of cancers via circulating biomarkers. Circulating tumor DNA (ctDNA), commonly termed "liquid biopsy," has emerged as a new, promising non-invasive tool to detect biomarkers in several cancers. The present review aimed to understand the biological concept of ctDNA and its potential as a biomarker in cancer studies and the clinical utility of this evolutionary diagnostic technique.
  2. Li YT, Chua MJ, Kunnath AP, Chowdhury EH
    Int J Nanomedicine, 2012;7:2473-81.
    PMID: 22701315 DOI: 10.2147/IJN.S30500
    Multidrug resistance, a major impediment to successful cancer chemotherapy, is the result of overexpression of ATP-binding cassette (ABC) transporters extruding internalized drugs. Silencing of ABC transporter gene expression with small interfering RNA (siRNA) could be an attractive approach to overcome multidrug resistance of cancer, although delivery of siRNA remains a major hurdle to fully exploit the potential of siRNA-based therapeutics. Recently, we have developed pH-sensitive carbonate apatite nanoparticles to efficiently carry and transport siRNA across the cell membrane, enabling knockdown of the cyclin B1 gene and consequential induction of apoptosis in synergy with anti-cancer drugs.
  3. Mahendra Raj S, Ravindran S, Braganza MC, Kaur K, Kunnath AP
    Med J Malaysia, 2021 Nov;76(6):811-813.
    PMID: 34806665
    BACKGROUND: Coeliac disease, an autoimmune enteropathy related to gluten sensitivity was hitherto thought to be rare in Asia. Recent data however suggests that Celiac disease may be under-diagnosed in Asia.

    OBJECTIVE: The aim of this audit was to determine the frequency of histological changes compatible with Coeliac disease among patients undergoing elective diagnostic oesaphago-gastro-duodenoscopy (OGDS) under the care of a single practitioner in a Malaysian hospital.

    MATERIALS AND METHODS: The archived endoscopically obtained duodenal biopsy specimens of 241 consecutive Malaysian subjects undergoing elective diagnostic (OGDS) were reviewed by a pathologist blinded to the clinical data. Based on intra-epithelial lymphocyte counts, crypt hyperplasia and villous atrophy, each subject was assigned to one of the categories of the Modified Marsh classification for the histological diagnosis of Coeliac disease. The clinical charts of all subjects were reviewed by a single gastroenterologist blinded to the findings of the histological review.

    RESULTS: Of the 241 study subjects, 132 (54.8%) were females. There were 56 (23.2%) Malays, 90 (37.3%) Chinese, 88 (36.5%) Indians and seven (2.9%) from the other category. The median age of the study sample was 49 years (range 15- 88 years). The OGDS was done as part of screening in 15(6.2%) subjects while in the remaining it was part of the investigation of a clinical problem. Based on histological findings, none of the subjects could be assigned to a modified Marsh class of >1. The prevalence of histological changes compatible with Coeliac disease in the study was 0% (binomial exact one-sided 97.5 % confidence interval 0- 1.52%).

    CONCLUSION: In conclusion, this audit provides no evidence that active Coeliac disease is significantly under-detected among symptomatic patients presenting for diagnostic OGDS. The possibility that a significant number may have potential coeliac disease cannot be excluded.

  4. Mailankot M, Kunnath AP, Jayalekshmi H, Koduru B, Valsalan R
    Clinics (Sao Paulo), 2009;64(6):561-5.
    PMID: 19578660
    INTRODUCTION: Mobile phones have become indispensable in the daily lives of men and women around the globe. As cell phone use has become more widespread, concerns have mounted regarding the potentially harmful effects of RF-EMR from these devices.

    OBJECTIVE: The present study was designed to evaluate the effects of RF-EMR from mobile phones on free radical metabolism and sperm quality.

    MATERIALS AND METHODS: Male albino Wistar rats (10-12 weeks old) were exposed to RF-EMR from an active GSM (0.9/1.8 GHz) mobile phone for 1 hour continuously per day for 28 days. Controls were exposed to a mobile phone without a battery for the same period. The phone was kept in a cage with a wooden bottom in order to address concerns that the effects of exposure to the phone could be due to heat emitted by the phone rather than to RF-EMR alone. Animals were sacrificed 24 hours after the last exposure and tissues of interest were harvested.

    RESULTS: One hour of exposure to the phone did not significantly change facial temperature in either group of rats. No significant difference was observed in total sperm count between controls and RF-EMR exposed groups. However, rats exposed to RF-EMR exhibited a significantly reduced percentage of motile sperm. Moreover, RF-EMR exposure resulted in a significant increase in lipid peroxidation and low GSH content in the testis and epididymis.

    CONCLUSION: Given the results of the present study, we speculate that RF-EMR from mobile phones negatively affects semen quality and may impair male fertility.

  5. Kunnath AP, Suodha Suoodh M, Chellappan DK, Chellian J, Palaniveloo K
    Br J Biomed Sci, 2024;81:12958.
    PMID: 39170669 DOI: 10.3389/bjbs.2024.12958
    The global issue of antimicrobial resistance poses significant challenges to public health. The World Health Organization (WHO) has highlighted it as a major global health threat, causing an estimated 700,000 deaths worldwide. Understanding the multifaceted nature of antibiotic resistance is crucial for developing effective strategies. Several physiological and biochemical mechanisms are involved in the development of antibiotic resistance. Bacterial cells may escape the bactericidal actions of the drugs by entering a physiologically dormant state known as bacterial persistence. Recent findings in this field suggest that bacterial persistence can be one of the main sources of chronic infections. The antibiotic tolerance developed by the persister cells could tolerate high levels of antibiotics and may give rise to persister offspring. These persister offspring could be attributed to antibiotic resistance mechanisms, especially in chronic infections. This review attempts to shed light on persister-induced antibiotic resistance and the current therapeutic strategies.
  6. Ng PQ, Ling LSC, Chellian J, Madheswaran T, Panneerselvam J, Kunnath AP, et al.
    Curr Pharm Des, 2020;26(36):4580-4590.
    PMID: 32520681 DOI: 10.2174/1381612826666200610111013
    Many plant-based bioactive compounds have been serving as the origin of drugs since long ago and many of them have been proven to have medicinal value against various chronic diseases, including, cancer, arthritis, hepatic diseases, type-2 diabetes and cardiovascular diseases. However, their clinical applications have been limited due to their poor water solubility, stability, low bioavailability and extensive transformation due to the first-pass metabolism. The applications of nanocarriers have been proven to be able to improve the delivery of bioactive phytoconstituents, resulting in the enhancement of various pharmacokinetic properties and thereby increasing the therapeutic value of phytoconstituents. These biocompatible nanocarriers also exert low toxicity to healthy cells. This review focuses on the uses and applications of different types of nanocarriers to enhance the delivery of phytoconstituents for the treatment of various chronic diseases, along with comparisons related to bioavailability and therapeutic efficacy of nano phytoconstituents with native phytoconstituents.
  7. Palaniveloo K, Yee-Yinn L, Jia-Qi L, Chelliah A, Sze-Looi S, Nagappan T, et al.
    Foods, 2021 Aug 20;10(8).
    PMID: 34441709 DOI: 10.3390/foods10081932
    Seaweeds are an important ingredient of functional foods recommended for daily food, due to their unique compositions and nutritional value. Padina tetrastromatica is a brown edible seaweed that is commonly found along the coastal regions of Peninsular Malaysia and consumed as food by some coastal communities. This study investigates the nutritional and antihyperglycaemic potential of P. tetrastromatica extracts, which is generally accepted as an important functional food. In our methodology, we induced diabetes intraperitoneally in experimental animals with a dose of 65 mg kg-1 body weight of streptozotocin. Oral treatment with 200 and 400 mg kg-1 of P. tetrastromatica ethanolic and ethyl acetate extracts were initiated, respectively, to experimental rats once daily for 18 days. Metformin was used as the positive control. Biochemical estimations and histopathological analysis were included in this study. Treatment with P. tetrastromatica extracts significantly lowered the plasma glucose levels in Streptozotocin-induced diabetic rats. In addition, P. tetrastromatica extract treatment also showed a significant reduction in serum alanine transaminase levels. However, no significant changes were observed in serum aspartate transaminase levels. The ethyl acetate extract of P. tetrastromatica at 400 mg kg-1 dose shows some nephroprotective effect, which is observed from the significant increase in the plasma albumin levels. Histopathological evaluation revealed no marked morphological changes in tissues of the isolated organs of the ethyl acetate extract-treated group, revealing the safe nature of P. tetrastromatica.
  8. Xin GLL, Khee YP, Ying TY, Chellian J, Gupta G, Kunnath AP, et al.
    Curr. Diab. Rep., 2019 03 23;19(5):22.
    PMID: 30905013 DOI: 10.1007/s11892-019-1144-3
    PURPOSE OF REVIEW: Type 1 diabetes (T1D) occurs when there is destruction of beta cells within the islets of Langerhans in the pancreas due to autoimmunity. It is considered a complex disease, and different complications can surface and worsen the condition if T1D is not managed well. Since it is an incurable disease, numerous treatments and therapies have been postulated in order to control T1D by balancing hyperglycemia control while minimizing hypoglycemic episodes. The purpose of this review is to primarily look into the current state of the available immunological therapies and their advantages for the treatment of T1D.

    RECENT FINDINGS: Over the years, immunological therapy has become the center of attraction to treat T1D. Immunomodulatory approaches on non-antigens involving agents such as cyclosporine A, mycophenolate mofetil, anti-CD20, cytotoxic T cells, anti-TNF, anti-CD3, and anti-thymocyte globulin as well as immunomodulative approaches on antigens such as insulin, glutamic acid decarboxylase, and heat shock protein 60 have been studied. Aside from these two approaches, studies and trials have also been conducted on regulatory T cells, dendritic cells, interleukin 2, interleukin 4, M2 macrophages, and rapamycin/interleukin 2 combination therapy to test their effects on patients with T1D. Many of these agents have successfully suppressed T1D in non-obese diabetic (NOD) mice and in human trials. However, some have shown negative results. To date, the insights into the management of the immune system have been increasing rapidly to search for potential therapies and treatments for T1D. Nevertheless, some of the challenges are still inevitable. A lot of work and effort need to be put into the investigation on T1D through immunological therapy, particularly to reduce complications to improve and enhance clinical outcomes.

  9. Qudus B Aroyehun A, Abdul Razak S, Palaniveloo K, Nagappan T, Suraiza Nabila Rahmah N, Wee Jin G, et al.
    Foods, 2020 Sep 18;9(9).
    PMID: 32961907 DOI: 10.3390/foods9091313
    Caulerpa racemosa (Forsskal) J. Agardh is a green seaweed used as food and folk medicine since ancient times in the Indo-Pacific region, particularly in southeast Asia. In this study, the proximate nutrient composition, phytochemical, anti-oxidant and anti-diabetic properties of sea grape C. racemosa collected from culture fishponds in Johor, Malaysia were analysed. The contents (dry weight basis) of carbohydrate, crude protein, crude lipids, ash and caloric value obtained were 33.42 ± 1.34%, 20.27 ± 0.14%, 4.20 ± 0.32%, 28.25 ± 0.27% and 2544.67 ± 7.04 cal g-1, respectively. The amino acid score (AAs) and biological protein value (213.43 mg g-1) indicated that C. racemosa presented a better protein quality. The most abundant fatty acids were C16:0 (palmitic acid: 63.27%), followed by C18:1 (oleic acid: 5.80%), and C18:2 ῳ6 (linoleic acid: 5.33%). The analysis of the ash content indicated that essential minerals and trace elements, such as Ca, Fe, and Mn, were present in the seaweed. The total phenolic content (TPC) and total flavonoid content (TFC) observed in the ethyl acetate extract were 17.88 ± 0.78 mg GAE g-1 and 59.43 ± 2.45 mg QE g-1, respectively. The ethyl acetate extract of C. racemosa demonstrated notable anti-diabetic activity in diabetic induced rats. The low (100 mg kg-1) and high (200 mg kg-1) doses of cultivated C. racemosa extract exhibited a significant decrease (p < 0.05) in blood glucose levels while preventing weight loss, reducing plasma AST, ALT levels as a sign of hepatoprotective effect and recording albumin levels similar to positive control in diabetic induced rats. The results support the usefulness of cultivated C. racemosa as a potential functional food.
  10. Chellappan DK, Chellian J, Rahmah NSN, Gan WJ, Banerjee P, Sanyal S, et al.
    Diabetes Metab Syndr Obes, 2023;16:2187-2223.
    PMID: 37521747 DOI: 10.2147/DMSO.S390741
    Diabetes mellitus (DM) is a chronic metabolic disorder recognized as a major health problem globally. A defective insulin activity contributes to the prevalence and expansion of DM. Treatment of DM is often hampered by limited options of conventional therapies and adverse effects associated with existing procedures. This has led to a spike in the exploration for potential therapeutic agents from various natural resources for clinical applications. The marine environment is a huge store of unexplored diversity of chemicals produced by a multitude of organisms. To date, marine microorganisms, microalgae, macroalgae, corals, sponges, and fishes have been evaluated for their anti-diabetic properties. The structural diversity of bioactive metabolites discovered has shown promising hypoglycaemic potential through in vitro and in vivo screenings via various mechanisms of action, such as PTP1B, α-glucosidase, α-amylase, β-glucosidase, and aldose reductase inhibition as well as PPAR alpha/gamma dual agonists activities. On the other hand, hypoglycaemic effect is also shown to be exerted through the balance of antioxidants and free radicals. This review highlights marine-derived chemicals with hypoglycaemic effects and their respective mechanisms of action in the management of DM in humans.
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