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Navigating therapeutic prospects by modulating autophagy in colorectal cancer

Rajendran D, Oon CE

Life Sci, 2024 Dec 01;358:123121.
PMID: 39389340 DOI: 10.1016/j.lfs.2024.123121

Colorectal cancer (CRC) remains a leading cause of death globally despite the improvements in cancer treatment. Autophagy is an evolutionarily conserved lysosomal-dependent degradation pathway that is critical in maintaining cellular homeostasis. However, in cancer, autophagy may have conflicting functions in preventing early tumour formation versus the maintenance of advanced-stage tumours. Defective autophagy has a broad and dynamic effect not just on cancer cells, but also on the tumour microenvironment which influences tumour progression and response to treatment. To add to the layer of complexity, somatic mutations in CRC including tumour protein p53 (TP53), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphatase and tensin homolog (PTEN) can render chemoresistance by promoting a pro-survival advantage through autophagy. Recent studies have also reported autophagy-related cell deaths that are distinct from classical autophagy by employing parts of the autophagic machinery, which impacts strategies for autophagy regulation in cancer therapy. This review discusses the molecular processes of autophagy in the evolution of CRC and its role in the tumour microenvironment, as well as prospective therapeutic methods based on autophagy suppression or promotion. It also highlights clinical trials using autophagy modulators for treating CRC, underscoring the importance of autophagy regulation in CRC therapy.
Fulltext Factors influences crude herbs use among patients with chronic diseases attending a government health clinic: a cross-sectional survey

Saw, Y. Y., Rajendran, D., Alicia, L. M. L., Chan, Y. L., Chow, Z. S., Roslan, A. Z., et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):52-52.
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Introduction: Crude herbs can be defined as raw plants materials (e.g. leaves, flowers, roots, etc.) which are not being/minimally processed or dried. Globally, particularly in Malaysia, the use of crude herbs has been increasing. The reasons were as an ailment of diseases underlying conditions and for general wellbeing. In this study, our aim was to investigate factors influences crude herbs use among older patients with chronic diseases. Methods: A cross-sectional survey was conducted using purposive sampling among patients attended government health clinic
at Klinik Kesihatan Kampar, Perak. Self-designed questionnaires were used to collect data and data was analysed using SPSS software (ver. 23). Results: A total of 441 participants were enrolled in this study, the response rate was 71.35%. Demographic characteristics of patients who consume crude herbs were; female (57.25%), Malays (45.06%), age between 50-59 years old (31.96%), secondary education level (49.1%), and earned income less than RM3000 (93.27%). Female gender was found associated with the use of crude herbs (p < 0.05). Other socio-demographic characteristics, such as age, race, education level, and salary range found not associated with crude herbs (p > 0.05). The common reasons given by patients to use crude herbs were; family influence, effectiveness in reducing sugar, and accessible and cheaper compared to commercialised herbal drugs. The prevalence of crude herbs use,
particularly among ageing patients is alarming. The physicians need to take into account on crude herbs used when prescribing medications. The use of crude herbs can be beneficial but yet can be detrimental if it is consumed while on prescribed medications. Conclusion: The findings of this study indicate that the survey area needs to broaden to other parts of Malaysia, particularly rural is warranted.
Chronic granulomatous mastitis with axillary lymphadenopathy in a nulliparous woman

Rajendran D, Chew BS, Wong MW, Cheong YT

Med J Malaysia, 2019 12;74(6):564-565.
PMID: 31929493

Chronic Granulomatous Mastitis (CGM) is a rare disorder and this generally occurs in young women with a recent history of lactation. Development of this disease in nulliparous women are rare with an incidence of 10%. Axillary lymphadenopathy is seen in 15% of cases diagnosed with CGM. We present a case of CGM in a 23- year-old nulliparous woman presenting with a breast mass and multiple axillary lymphadenopathy. To the best of our knowledge there are no documented cases of both these rare clinical features occurring simultaneously. The use of oral steroids prevented surgery and effectively induced remission.
Fulltext The potential use of Azolla pinnata as an alternative bio-insecticide

Ravi R, Rajendran D, Oh WD, Mat Rasat MS, Hamzah Z, Ishak IH, et al.

Sci Rep, 2020 11 06;10(1):19245.
PMID: 33159109 DOI: 10.1038/s41598-020-75054-0

Four different tests showed the effectiveness of Azolla pinnata plant extracts against Aedes aegypti and Aedes albopictus mosquitoes. In the adulticidal test, there was a significant increase in mortality as test concentration increases and A. pinnata extracts showed LC50 and LC95 values of 2572.45 and 6100.74 ppm, respectively, against Ae. aegypti and LC50 and LC95 values of 2329.34 and 5315.86 ppm, respectively, against Ae. albopictus. The ovicidal test showed 100% eggs mortality for both species tested for all the concentrations tested at 1500 ppm, 1000 ppm, 500 ppm, 250 ppm and 125 ppm. Both tested samples of Ae. aegypti and Ae. albopictus did not lay any eggs in the plastic cups filled with the A. pinnata extract but instead opted to lay eggs in the plastic cups filled with water during the oviposition deterrence test. Similarly, the non-choice test of Ae. aegypti mosquitoes laid eggs on the sucrose solution meant for the nutrient source of the mosquitoes instead of in the plastic cup that was designed to facilitate oviposition filled with the extract. This clearly indicates the presence of bioactive compounds which are responsible in adulticidal and ovicidal activity in Aedes mosquitoes and at the same time inducing repellence towards the mosquitoes. The LC-MS results showed mainly three important chemical compounds from A. pinnata extracts such as 1-(O-alpha-D-glucopyranosyl)-(1,3R,25R)-hexacosanetriol, Pyridate and Nicotinamide N-oxide. All these chemicals have been used for various applications such as both emulsion and non-emulsion type of cosmetics, against mosquito vector such as Culex pipens and Anopheles spp. Finally, the overall view of these chemical components from A. pinnata extracts has shown the potential for developing natural product against dengue vectors.
Roles of probiotics against HPV through the gut-vaginal axis

Xu P, Mageswaran UM, Nisaa AA, Balasubramaniam SD, Rajendran D, Ismail EHBE, et al.

Int J Gynaecol Obstet, 2024 Nov 09.
PMID: 39520180 DOI: 10.1002/ijgo.16005

Human papillomavirus (HPV) is a sexually transmitted virus, whose persistent infection is the main reason for invasive cervical cancer (ICC), which is the fourth most common type of cancer in women, with more than 500 000 new cases every year. After infection, various alterations occur in the host, facilitating the virus's evasion of immune system clearance and promoting its proliferation. Oral probiotic consumption can influence the whole body's immunity, inflammatory reflection, neural, endocrine humoral, metabolic pathways and other organs by adjusting the components of gut microbiota (GM). Some evidence shows there is a tight connection between GM and vaginal microbiota (VM), which is referred to as the gut-vaginal axis. This review investigates the potential role of probiotics in clearing HPV via the gut-vagina axis, emphasizing the effectiveness of Lactobacillus in preventing vaginal diseases and suggesting its potential for HPV clearance. Understanding the role of probiotics in the gut-vagina axis could pave the way for new strategies to reduce and eliminate HPV and related diseases.
Fulltext Analysis of chemical compositions and larvicidal activity of nut extracts from Areca catechu Linn against Aedes (Diptera: Culicidae)

Bharathithasan M, Ravindran DR, Rajendran D, Chun SK, Abbas SA, Sugathan S, et al.

PLoS One, 2021;16(11):e0260281.
PMID: 34843539 DOI: 10.1371/journal.pone.0260281

BACKGROUND: There is a growing need to use green alternative larvicidal control for Aedes larvae compared to chemical insecticides. Substantial reliance on chemical insecticides caused insecticide resistance in mosquito populations. Thus, research for alternate chemical compounds from natural products is necessary to control Aedes larvae. This study explores the analysis of chemical compositions from Areca catechu nut as a potential larvicide for Aedes (Diptera: Culicidae).
METHODS: The Areca catechu nut collected from Ipoh, Perak, Malaysia was grounded into powder and used for Soxhlet extraction. The chemical analysis of the extracts and their structures were identified using the GCMS-QP2010 Ultra (Shimadzu) system. National Institute of Standards and Technology (NIST) Chemistry WebBook, Standard Reference Database 69 (https://webbook.nist.gov/chemistry/) and PubChem (https://pubchem.ncbi.nlm.nih.gov/), the two databases used to retrieve the synonyms, molecular formula, molecular weight, and 2-dimensional (2D) structure of chemical compounds. Next, following WHO procedures for larval bioassays, the extracts were used to asses larvicidal activity against early 4th instar larvae of Aedes aegypti and Aedes albopictus.
RESULTS: The larvicidal activities were observed against early 4th stage larvae with different concentrations in the range from 200 mg/L to 1600 mg/L. The LC50 and LC95 of Aedes aegypti were 621 mg/L and 2264 mg/L respectively; whereas the LC50 and LC95 of Aedes albopictus were 636 mg/L and 2268 mg/L respectively. Mortality was not observed in the non-target organism test. The analysis using gas chromatography and mass spectrometer recovered several chemical compounds such as Arecaidine, Dodecanoic acid, Methyl tetradecanoate, Tetradecanoic acid , and n-Hexadecanoic acid bioactive components. These chemical constituents were used as additive formulations in pesticides, pest control, insect repellent, and insecticidal agents.
CONCLUSIONS: Our study showed significant outcomes from the extract of Areca catechu nut and it deserves further investigation in relation to chemical components and larvicidal actions between different species of Aedes mosquitoes. Even though all these findings are fundamental, it may have some interesting potentials to be developed as natural bio-larvicidal products.
Fulltext Vaginal Infections during Pregnancy Increase Breast Milk Microbiome Alpha Diversity and Alter Taxonomic Composition

Nisaa AA, Oon CE, Sreenivasan S, Balakrishnan V, Rajendran D, Tan JJ, et al.

Prev Nutr Food Sci, 2023 Mar 31;28(1):1-9.
PMID: 37066035 DOI: 10.3746/pnf.2023.28.1.1

We previously reported that breast milk from women with (W) or without (WO) vaginal yeast infection during pregnancy differs in its immunological and antimicrobial properties, especially against pathogenic vaginal Candida sp.. Here, we investigated the differences in microbiota profiles of breast milk from these groups. Seventy-two breast milk samples were collected from lactating mothers (W, n=37; WO, n=35). The DNA of bacteria was extracted from each breast milk sample for microbiota profiling by 16S rRNA gene sequencing. Breast milk from the W-group exhibited higher alpha diversity than that from the WO-group across different taxonomic levels of class (P=0.015), order (P=0.011), family (P=0.020), and genus (P=0.030). Compositional differences between groups as determined via beta diversity showed marginal differences at taxonomic levels of phylum (P=0.087), family (P=0.064), and genus (P=0.067). The W-group showed higher abundances of families Moraxellaceae (P=0.010) and Xanthomonadaceae (P=0.008), and their genera Acinetobacter (P=0.015), Enhydrobacter (P=0.015), and Stenotrophomonas (P=0.007). Meanwhile, the WO-group showed higher abundances of genus Staphylococcus (P=0.046) and species Streptococcus infantis (P=0.025). This study shows that, although breast milk composition is affected by vaginal infection during pregnancy, this may not pose a threat to infant growth and development.