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Uncovering the impact of alcohol on internal organs and reproductive health:Exploring TLR4/NF-kB and CYP2E1/ROS/Nrf2 pathways

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Animal Models and Experimental medicine 2024年第4期7卷 444-459页

作者： Eason Qi Zheng Kong Vetriselvan Subramaniyan Natasha Sura Anak Lubau Pharmacology Unit Jeffrey Cheah School of Medicine and Health SciencesMonash University MalaysiaSubang JayaSelangorMalaysia Center for Global health Research Saveetha Medical CollegeSaveetha Institute of Medical and Technical SciencesChennaiTamil NaduIndia

This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health,elucidating the underlying mechanisms involving the Toll-like receptor 4(TLR4)/Nuclear factor kappa light chain enhancer of activated B cells(NF-kB)pathway and the Cytochrome P4502E1(CYP2E1)/reactive oxygen spe-cies(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)*** TLR4/NF-kB pathway,crucial for inflammatory and immune responses,triggers the production of pro-inflammatory agents and type-1 interferon,disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to ***-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns(PAMPs),leading to liver cell infection and subsequent ***,CYP2E1-mediated alcohol metabolism gen-erates ROS,causing oxidative stress and damaging cells,lipids,proteins,and deoxy-ribonucleic acid(DNA).To counteract this inflammatory imbalance,Nrf2 regulates gene expression,inhibiting inflammatory progression and promoting antioxidant *** alcohol intake results in elevated liver enzymes(ADH,CYP2E1,and catalase),ROS,NADH,acetaldehyde,and acetate,leading to damage in vital organs such as the heart,brain,and ***,alcohol negatively affects reproduc-tive health by inhibiting the hypothalamic-pituitary-gonadal axis,causing infertility in both men and *** findings underscore the profound health concerns associated with alcohol-induced damage,emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ im-pacts of alcohol consumption.

关键词： alcohol health impact inflammation metabolism molecular pathways

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Autophagy and mitophagy as potential therapeutic targets in diabetic heart condition: Harnessing the power of nanotheranostics

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Asian Journal of Pharmaceutical sciences 2024年第3期19卷 83-105页

作者： Sagnik Nag Oishi Mitra Bhanu Maturi Simran Preet Kaur Ankita Saini Muskan Nama Soumik Roy Souvik Samanta Leena Chacko Rohan Dutta Suresh Babu Sayana Vetriselvan Subramaniyan Jasvinder Singh Bhatti Ramesh Kandimalla Jeffrey cheah school of medicine and health sciences Monash University Malaysia Department of Bio-sciences School of Bio-Sciences&Technology (SBST)Vellore Institute of Technology (VIT) Department of Internal medicine University of Alabama at Birmingham Department of Microbiology University of Delhi (South Campus) Department of Biotechnology Indian Institute of TechnologyHyderabad (IIT-H) Bio Analytical Lab Meso Scale Discovery Department of Pharmacology Government Medical College Laboratory of Translational medicine and Nanotherapeutics Department of Human Genetics and Molecular MedicineSchool of Health SciencesCentral University of Punjab Department of Biochemistry Kakatiya Medical College

Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC), which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies. Despite significant progress in reducing mortality rates from cardiovascular diseases(CVDs), heart failure remains a major cause of increased morbidity among diabetic patients. These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components, and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment. While a variety of conventional diagnostic and therapeutic strategies are available, DHC continues to present a significant ***-of-care diagnostics, supported by nanobiosensing techniques, offer a promising alternative for these complex scenarios. Although conventional medications have been widely used in DHC patients, they raise several concerns regarding various physiological aspects. Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC, offering a promising approach to deliver drugs beyond the limitations of traditional therapies. This article aims to explore the potential connections between autophagy, mitophagy and DHC, while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.

关键词： Autophagy Diabetes Diabetic heart condition Mitophagy Nanotheranostics Nanomedicine

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Identification of commonly regulated protein targets and molecular pathways in PC-3 and DU145 androgen-independent human prostate cancer cells treated with the curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one

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Asian Pacific Journal of Tropical Biomedicine 2018年第9期8卷 436-445页

作者： Kamini Citalingam Faridah Abas Nordin H.Lajis Iekhsan Othman Rakesh Naidu jeffery cheah school of medicine and health sciences Monash University Malaysia Jalan Lagoon Selatan Laboratory of Natural Products Faculty of Science Universiti Putra Malaysia Department of Food Science Faculty of Food Science and Technology Universiti Putra Malaysia

Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathways that contributed to the anticancer activity of ***: PC-3 and DU145 cells were treated with 3 × EC_(50)(15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass *** differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically *** regulated proteins were ranked by fold change and identified as common protein targets of ***: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with ***, the expressions of CH60 and HS71 A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 *** analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/***: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.

关键词： Androgen-independent prostate cancer Diarylpentanoid Proteomics profiling Mass spectrometry Pathway analysis

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PH-responsive strontium nanoparticles for targeted gene therapy against mammary carcinoma cells

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Asian Journal of Pharmaceutical sciences 2021年第2期16卷 236-252页

作者： Athirah Bakhtiar Ezharul Hoque Chowdhury school of Pharmacy Monash University MalaysiaSelangor 47500Malaysia Jeffrey cheah school of medicine and health sciences Monash University MalaysiaSelangor 47500Malaysia

Genetic intervention via the delivery of functional genes such as plasmid DNA(pDNA)and short-interfering RNA(siRNA)offers a great way to treat many single or multiple genetic defects effectively,including mammary *** of naked therapeutic genes or siRNAs is,however,short-lived due to biological clearance by scavenging nucleases and circulating *** cellular internalization of negatively-charged nucleic acids further causes low transfection or silencing *** of safe and effectual gene vectors is therefore undeniably crucial to the success of nucleic acid *** nanoparticles have attracted considerable attention in the recent years due to their high loading capacity and encapsulation *** we introduce strontium salt-based nanoparticles,namely,strontium sulfate,strontium sulfite and strontium fluoride as new inorganic *** strontium salt particles were found to be nanosized with high affinity towards negatively-charged pDNA and *** of the particles was seen with a drop in pH,suggesting their capacity to respond to pH change and undergo dissolution at endosomal pH to release the genetic *** the particles are relatively nontoxic towards the cells,siRNA-loaded SrF 2 and SrSO 3 particles exerted superior transgene expression and knockdown activity of MAPK and AKT,leading to inhibition of their phosphorylation to a distinctive extent in both MCF-7 and 4T1 *** salt nanoparticles have thus emerged as a promising tool for applications in cancer gene therapy.

关键词： Strontium Gene therapy Breast cancer SiRNA Nanoparticles

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Strategies to assemble therapeutic and imaging molecules into inorganic nanocarriers

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Frontiers of Materials Science 2022年第3期16卷 101-144页

作者： Sheikh Tanzina HAQUE Mark M.BANASZAK HOLL Ezharul Hoque CHOWDHURY Jeffrey cheah school of medicine and health sciences Monash University MalaysiaJalan Lagoon SelatanBandar Sunway47500 Subang JayaSelangorMalaysia Department of Chemical and Biological Engineering Monash UniversityClaytonVictoria 3800Australia health and Wellbeing Cluster Global Asia in the 21st Century(GA21)PlatformJeffrey Cheah School of Medicine and Health SciencesMonash University MalaysiaJalan Lagoon SelatanBandar Sunway47500 Subang JayaSelangorMalaysia

Inorganic nanocarriers are potent candidates for delivering conventional anticancer drugs,nucleic acid-based therapeutics,and imaging agents,influencing their blood half-lives,tumor targetability,and *** addition to the high surface area-to-volume ratio,they exhibit excellent scalability in synthesis,controllable shape and size,facile surface modification,inertness,stability,and unique optical and magnetic ***,only a limited number of inorganic nanocarriers have been so far approved for clinical applications due to burst drug release,poor target specificity,and *** overcome these barriers,understanding the principles involved in loading therapeutic and imaging molecules into these nanoparticles(NPs)and the strategies employed in enhancing sustainability and targetability of the resultant complexes and ensuring the release of the payloads in extracellular and intracellular compartments of the target site is of paramount ***,we will shed light on various loading mechanisms harnessed for different inorganic NPs,particularly involving physical entrapment into porous/hollow nanostructures,ionic interactions with native and surface-modified NPs,covalent bonding to surface-functionalized nanomaterials,hydrophobic binding,affinity-based interactions,and intercalation through co-precipitation or anion exchange reaction.

关键词： inorganic nanoparticle cancer ionic interaction covalent bonding affinity interaction intercalation

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Identification of commonly regulated genes in HPV18-and HPV16-infected cervical cancer cells treated with the curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one

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Asian Pacific Journal of Tropical Biomedicine 2018年第1期8卷 44-51页

作者： Felicia Paulraj Faridah Abas Nordin H.Lajis Iekhsan Othman Sharifah Syed Hassan Rakesh Naidu Jeffrey cheah school of medicine & health sciences Monash University Malaysia Laboratory of Natural Products Faculty of Science Universiti Putra Malaysia Department of Food Science Faculty of Food Science and Technology Universiti Putra Malaysia

Objective: To identify commonly regulated genes in HPV-infected He La and Ca Ski cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17) and to explore potential mechanisms that underlie its cytotoxic, anti-proliferative and apoptotic activity. Methods: He La and Ca Ski cells were treated with 2×EC50 and 3×EC50 doses of MS17 for 24 h and the RNA extracts were subjected to one-colour microarray-based gene expression profiling. Pair-wise significant genes(false discovery rate-corrected, P<0.05) were analysed for fold change(FC) compared to control samples. Differentially expressed genes with FC≥2.0(up-regulated; FC≥2.0 and down-regulated; FC≤-2.0) compared to the control samples were filtered through and analysed to create a global gene expression profile. Mutually regulated genes were ranked by FC and categorised by gene ontology. Results: Our data indicated dose-dependent regulation by MS17 and identified top 20 mutually upand down-regulated genes each in He La and Ca Ski cells. Amongst these 17 were commonly regulated in both cell lines. These include the up-regulation of CCL26, DEFB103 B, IL1 RL1, LY96, GCNT3, MMP10, MMP3, GADD45 G and HSPA6, and the down-regulation of TENM2, NEBL, KIFC1, CTDSP1, IGFBP5, LTBP1, NREP and MXD3. These genes were associated with key biological functions that were proposed to mediate the anticancer activity of MS17 in cervical cancer cells such as immune response, metabolic processes, proteolysis, programmed cell death, unfolded protein response, cell adhesion, cytoskeletal organisation, phosphatase activity, signal transduction and transcription regulator activity. Conclusions: Identification of seventeen common genes modulated by MS17 could be used as potential therapeutic targets in both cervical cancer cell lines and the findings of this study could be used to present an insight into the potential antitumor activity of MS17 in cervical cancer.

关键词： Diarylpentanoid Cervical cancer Gene expression profiling Microarray Curcumin analogue

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Enhancing Students’ Learning about healthy Living through Community Participation

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Open Journal of Preventive medicine 2014年第10期4卷 771-778页

作者： Anil Gandhi Hari Kumar Darnal Ahmad Munir Qureshi Suneet Sood Rusli Bin Nordin Clinical school Johor Bahru Jeffrey Cheah School of Medicine and Health Sciences Monash University Malaysia

Introduction: The health Enhancement Module (HEM) is taught as a core curriculum for all medical students at Monash University since 2002. In 2012 we moved the year three content of the program into a community setting, calling it the health Enhancement Carnival (HEC). At the carnival, our undergraduates interacted with school students, their teachers, and their parents, involving them in a mix of discussions, poster presentations, and video presentations. In this paper we present our experience with the HEC. Specifically, we looked at the following two measures: how did the HEC influence the knowledge, attitude, and practice of healthy living among medical students? And, what were the learning experiences of the students during the HEC? Methods: Five themes (exercise, food, healthy sleep, workplace stress and ageing) were divided among students. They were asked to develop those themes with the help of posters, power point presentations, community talks as well as video presentations. The carnival was held in the setting of two nearby children’s schools. Students were evaluated by a panel of examiners with regards to learning objectives as well as preparation and presentation. As part of evaluation, we developed 2 questionnaires. The HEP healthy Living Questionnaire provided feedback on how the program had improved students’ knowledge, attitudes, and practice of healthy living. The HEP Learning Style Questionnaire covered twelve areas, including collegiality, environment, leadership, community interaction and other facets of learning style. Analyses were performed using the IBM SPSS Statistics version 20 software in the Clinical school Johor Bahru. Results: 1) Influence of HEC on the knowledge, attitude, and practice of healthy living among medical students. From the interviews, the judges gave the students mean ratings of 4.0/5. We also received 77 out of 127 feedback questionnaires (response rate: 60.6%) from the students. Most students (range: 49.35% to 55.84%) w

关键词： health Enhancement Program health Enhancement Carnival Knowledge Attitude and Practice Blended Learning healthy Living

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Review Paper: Association between Social Network and Obesity among Adult Population

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Open Journal of Endocrine and Metabolic Diseases 2022年第2期12卷 20-46页

作者： Xiao Yi Brenda Lee Nur Wafiah Yusof Naganathan Kathiresan Pillai Christina Gertrude Yap Nowrozy Kamar Jahan Jeffrey cheah school of medicine and health sciences Monash University Malaysia Kuala Lumpur Malaysia

Objectives: Our main objective is to establish an association between obesity and social networks among the adult population as well as understanding the underlying mechanisms. We aim to provide suggestions for the development of future interventions to treat obesity. Methods: We carried out a literature search from 4 databases: PubMed, Embase, Scopus and Web of Science. We conducted a systematic search targeting on 3 main concept terms—“social network”, “obesity” and “adult”. A final pool of 11 articles best fitted for our topic was included. Results: We have established a clear association between obesity and social networks. Single women with the co-living arrangement have a higher waist circumference (WC), consistent with a higher predisposition to obesity seen among single individuals but lone living divorced men had lower WC compared to those with partners. Women with high incomes are less likely to be obese in comparison to highly social men with low income. The degree of the effect on social networks and obesity was inconclusive due to differences in the study population. Generally, women with low social participation tend to be obese. However, non-partnered women consistently showed a higher WC in comparison to their partnered counterparts regardless of participation rates except for divorced women. Living in a neighborhood with access to active transportation, high socioeconomic status, increased levels of social trust and social support reduces the prevalence of obesity. Mechanisms of cultural ideals, nature of employment, stress, gender, self-selection, network influence, social contagion and shared built environment may have contributed to the variation in results obtained. Conclusion: Association between social network and obesity exists. However, its overall effect on body weight is affected by a variety of factors. Sociodemographic factors and network characteristics of the population may influence the impacts on body weight. Therefore, a good unders

关键词： Social Network Obesity Adults

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Growth factor receptors: promising drug targets in cancer

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Journal of Cancer Metastasis and Treatment 2015年第1期1卷 190-200页

作者： Snigdha Tiash Ezharul Hoque Chowdhury Jeffrey cheah school of medicine and health sciences Faculty of MedicineNursing and Health SciencesMonash University46150 Bandar SunwaySelangorMalaysia

Genetic,epigenetic and somatic changes deregulate the expression of growth factor receptors(GFRs),leading to cancer initiation and *** cell growth and survival are orchestrated by clonal expansion and evasion of apoptotic signals in cancer *** growth of cells is further supported by angiogenesis and metastasis to distant *** expression of GFRs also contributes to the development of ***,therapeutics to target GFRs is a potentially attractive molecular approach to treat cancer more *** this review,we have discussed the contribution of GFRs to cancer development and addressed molecular approaches undertaken to inhibit GFR-mediated pathways.A wide number of monoclonal antibodies(mAbs)and protein kinase inhibitors targeting these GFR-mediated functions are in clinical trials to treat human ***,most drugs that target GFRs lead to the development of drug resistance and generate adverse *** acid-based therapeutics,*** interfering RNA(siRNA)could be harnessed to selectively silence GFR genes in cancer *** polymer,liposome-based nanocarriers,and the most recently developed pH-sensitive inorganic carbonate apatite nanoparticles have been used in cell culture and preclinical trials for cytoplasmic delivery of the siRNAs targeting different GFR ***-based therapeutics have been shown to have signifi cant potential to suppress GFR expression and functions and thus could be developed as molecular ***-targeting of tumors at different levels by combining various approaches along with chemotherapy would be a promising therapeutic approach to fight the *** nanocarriers capable of entrapping siRNA,mAb,GFR inhibitors and classical drugs targeting GFR have potential therapeutic applications.

关键词： Carbonate apatite nanoparticles growth factor receptor monoclonal antibodies protein kinase inhibitor short interfering RNA tyrosine kinase inhibitor

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Melioidosis:a rare cause of anterior chest wall abscess

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Asian Pacific Journal of Tropical medicine 2010年第3期3卷 241-243页

作者： Rashidi Ahmad Azhar Amir Hamzah Ahmad Kasfi Abdul Rahman Phee Kheng cheah Department of Emergency medicine School of Medical SciencesUSM Health Campus Department of Surgery School of Medical SciencesUSM Health Campus Infectious Unit Department of MedicineHospital Kuala Terengganu

Melioidosis is an unusual tropical infectious disease caused by the gram-negative bacterium Burkholderia pseudomallei,which was formerly known as Pseudomonas pseudomallei. Melioidosis is characterized by abscess formation and it may manifest in any part of the human body,however,musculoskeletal melioidosis is uncommon and chest wall melioidosis is very rare. To determine the exact organism based solely on clinical presentation poses a great challenge to the ***,delay administration of antibiotic may be *** describe a diabetic patient who had anterior chest wall melioidosis that mimics Staphylococcus aureus infection.A description of his presentation and management,along with a review of literature is presented.

关键词： Melioidosis Chest wall abscess Diagnositic challenge

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