Understanding exposomes and its relation with cancer risk in Malaysia based on epidemiological evidence: a narrative review.

The prevalence of cancer is increasing globally, and Malaysia is no exception. The exposome represents a paradigm shift in cancer research, emphasizing the importance of a holistic approach that considers the cumulative effect of diverse exposures encountered throughout life. The exposures include dietary factors, air and water pollutants, occupational hazards, lifestyle choices, infectious agents and social determinants of health. The exposome concept acknowledges that each individual's cancer risk is shaped by not only their genetic makeup but also their unique life experiences and environmental interactions. This comprehensive review was conducted by systematically searching scientific databases such as PubMed, Scopus and Google Scholar, by using the keywords "exposomes (environmental exposures AND/OR physical exposures AND/OR chemical exposures) AND cancer risk AND Malaysia", for relevant articles published between 2010 and 2023. Articles addressing the relationship between exposomes and cancer risk in the Malaysian population were critically evaluated and summarized. This review aims to provide an update on the epidemiological evidence linking exposomes with cancer risk in Malaysia. This review will provide an update for current findings and research in Malaysia related to identified exposomes-omics interaction and gap in research area related to the subject matter. Understanding the interplay between complex exposomes and carcinogenesis holds the potential to unveil novel preventive strategies that may be beneficial for public health.

The Effects of 12 Weeks Colostrum Milk Supplementation on the Expression Levels of Pro-Inflammatory Mediators and Metabolic Changes among Older Adults: Findings from the Biomarkers and Untargeted Metabolomic Analysis.

Senescence is a normal biological process that is accompanied with a series of deteriorations in physiological function. This study aimed to investigate the effects of bovine colostrum milk supplementation on metabolic changes and the expression of various biomarkers on inflammation, antioxidant and oxidative damage, nutrient metabolism, and genomic stability among older adults. Older adults (50-69 years old) who participated in the 12-week randomized, double-blinded, placebo-controlled trial were instructed to consume the IgCo bovine colostrum-enriched skim milk or regular skim milk (placebo) twice daily. Following 12 weeks of intervention, participants in the intervention group had lower expression levels in pro-inflammatory mediators (CRP, IL-6, and TNF-α), with significant (p < 0.05) interaction effects of the group and time observed. However, no significant interaction effect was observed in the vitamin D, telomerase, 8-OHdG, MDA, and SOD activities. UPLC-MS-based untargeted metabolomics analysis revealed that 22 metabolites were upregulated and 11 were downregulated in the intervention group compared to the placebo group. Glycerophospholipid metabolism, along with cysteine and methionine metabolism were identified as the potential metabolic pathways that are associated with bovine colostrum milk consumption. In conclusion, consuming bovine colostrum milk may induce metabolic changes and reduce the expression of various pro-inflammatory mediators, thus improving the immune function in older adults.

Efficacy of zinc carnosine in the treatment of colorectal cancer and its potential in combination with immunotherapy in vivo.

BACKGROUND: A complex of Zn and carnosine, called Zinc-L-carnosine (ZnC), enjoys a wide application as part of a Zn supplement therapeutic method as well as in treating peptic ulcers. However, researches fail to confirm the biological functions possessed by ZnC as well as tumor immune microenvironment in colorectal cancer (CRC). METHODS: Cell counting kit 8(CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell and wound healing assays were conducted to study the influence of ZnC in the proliferating, invading and migrating processes of CRC cell lines (HCT116, LOVO) in vitro. The antitumor activity ZnC as well as its effects on tumor immune microenvironment were then assessed using CRC subcutaneous tumors in the C57BL/6 mouse model. RESULTS: According to CCK8, EdU, transwell and wound healing assays, ZnC inhibited CRC cell lines in terms of proliferation, invasion and migration. ZnC could inhibit miR-570 for up-regulating PD-L1 expression. In vivo experiments showed that gavage (100 mg/kg, once every day) of ZnC inhibited the tumor growth of CRC, and the combination of ZnC and anti-PD1 therapy significantly improved the efficacy exhibited by anti-PD1 in treating CRC. In addition, mass cytometry results showed that immunosuppressive cells including regulatory T cells (tregs), bone marrow-derived suppressor cells (MDSC), and M2 macrophages decreased whereas CD8+ T cells elevated after adding ZnC. CONCLUSIONS: The present study reveals that ZnC slows the progression of CRC by inhibiting CRC cells in terms of proliferation, invasion and migration, meanwhile up-regulating PD-L1 expression via inhibiting miR-570. The ZnC-anti-PD1 co-treatment assists in synergically increasing anti-tumor efficacy in CRC therapy.

Zinc carnosine: Frontiers advances of supplement for cancer therapy.

Zinc (Zn) has an existence within large quantities in the human brain, while accumulating within synaptic vesicle. There is growing evidence that Zn metabolic equilibrium breaking participates into different diseases (e.g., vascular dementia, carcinoma, Alzheimer's disease). Carnosine refers to an endogenic dipeptide abundant in skeletal muscle and brains and exerts a variety of positive influences (e.g., carcinoma resistance, crosslinking resistance, metal chelation and oxidation limitation). A complex of Zn and carnosine, called Zinc-L-carnosine (ZnC), has been extensively employed within Zn supplement therapeutic method and the treating approach for ulcers. ZnC has been shown to play a variety of roles in the body, including inhibiting intracellular reactive oxygen species(ROS) and free radical levels, inhibiting inflammation, supplementing zinc enzymes and promoting wound healing and mucosal cell repair. The present study conducting a reviewing process for the advances of ZnC in tumor adjuvant therapy.

Antimutagenic, Cytoprotective and Antioxidant Properties of Ficus deltoidea Aqueous Extract In Vitro.

Ficus deltoidea var. deltoidea is used as traditional medicine for diabetes, inflammation, and nociception. However, the antimutagenic potential and cytoprotective effects of this plant remain unknown. In this study, the mutagenic and antimutagenic activities of F. deltoidea aqueous extract (FDD) on both Salmonella typhimurium TA 98 and TA 100 strains were assessed using Salmonella mutagenicity assay (Ames test). Then, the cytoprotective potential of FDD on menadione-induced oxidative stress was determined in a V79 mouse lung fibroblast cell line. The ferric-reducing antioxidant power (FRAP) assay was conducted to evaluate FDD antioxidant capacity. Results showed that FDD (up to 50 mg/mL) did not exhibit a mutagenic effect on either TA 98 or TA 100 strains. Notably, FDD decreased the revertant colony count induced by 2-aminoanthracene in both strains in the presence of metabolic activation (p < 0.05). Additionally, pretreatment of FDD (50 and 100 µg/mL) demonstrated remarkable protection against menadione-induced oxidative stress in V79 cells significantly by decreasing superoxide anion level (p < 0.05). FDD at all concentrations tested (12.5-100 µg/mL) exhibited antioxidant power, suggesting the cytoprotective effect of FDD could be partly attributed to its antioxidant properties. This report highlights that F. deltoidea may provide a chemopreventive effect on mutagenic and oxidative stress inducers.

The stingless bee honey protects against hydrogen peroxide-induced oxidative damage and lipopolysaccharide-induced inflammation in vitro.

Oxidative stress, DNA damage, and unresolved inflammation are the predisposing factors of many chronic and degenerative diseases, including cancer. Stingless bee honey (SBH) is recognized to have high medicinal value by traditional medicine practitioners and has been used to treat various illnesses traditionally. This study aimed to determine the antioxidant, anti-inflammatory, and genoprotective effects of SBH by using in vitro cell culture models. The sugar content, total phenolic content, radical scavenging activity, and ferric reducing antioxidant power (FRAP) of SBH were determined in this study. Then, the protective effect of SBH against hydrogen peroxide (H2O2)-induced cell death and DNA damage was studied by using WIL2-NS human lymphoblastoid cell line, while the lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages cell line was used to study the anti-inflammatory effects of SBH. Results from this present study showed that the major sugar contents of SBH were fructose (19.39 + 0.01%) and glucose (14.03 ± 0.03%). Besides, the total phenolic content, the radical scavenging activity, and the FRAP value of SBH were 15.38 ± 0.02 mg GAE/100 g of honey, 34.04 ± 0.21%, and 206.77 + 1.76 µM AAE/100 g honey respectively. Pretreatment with SBH protected WIL2-NS cells from H2O2-induced cell death and DNA damage (p < 0.001). Moreover, SBH was also able to attenuate the production of nitric oxide by inhibiting the expression of inducible nitric oxide synthase in LPS-induced RAW 264.7 cells (p < 0.001). In conclusion, SBH is rich in total phenolic content and possesses strong antioxidant, anti-inflammatory, and genoprotective properties. Our current findings suggest that SBH might be useful in the prevention and treatment of many diseases caused by oxidative stress and inflammation assuming the observed effects are also achievable in vivo.

Neuroprotection of Tropical Fruit Juice Mixture via the Reduction of iNOS Expression and CRH Level in ß-Amyloid-Induced Rats Model of Alzheimer's Disease.

This study aimed to determine the effects of tropical fruit juice mixture (pomegranate, white guava, and Roselle) on biochemical, behavioral, and histopathological changes of ß-amyloid- (Aß-) induced rats. Formulation 8 (F8) of tropical fruit juice mixture was chosen for this present study due to its high phenolic content and antioxidant capacity. Forty Wistar male rats were divided into five groups: dPBS (sham-operated control), dAß (Aß control), JPBS (F8 and PBS), JAß (F8 and Aß), and IBFAß (ibuprofen and Aß). F8 (5 ml/kg BW), and ibuprofen (10 ml/kg BW) was given orally daily for four weeks before the intracerebroventricular infusion of Aß for two weeks. Histological analysis and neuronal count of hippocampus tissue in the Cornu Ammonis (CA1) region showed that supplementation with F8 was able to prevent Aß-induced tissue damage and neuronal shrinkage. However, no significant difference in locomotor activity and novel object recognition (NOR) percentage was detected among different groups at day 7 and day 14 following Aß infusion. Only effect of time differences (main effect of day) was observed at day 7 as compared to day 14, where reduction in locomotor activity and NOR percentage was observed in all groups, with F (1, 7) = 6.940, p < 0.05 and F (1, 7) = 7.152, p < 0.05, respectively. Besides, the MDA level of the JAß group was significantly lower (p < 0.01) than that of the dPBS group. However, no significant changes in SOD activity were detected among different groups. Significant reduction in plasma CRH level (p < 0.05) and iNOS expression (p < 0.01) in the brain was detected in the JAß group as compared to the dAß group. Hence, our current findings suggest that the tropical fruit juice mixture (F8) has the potential to protect the rats from Aß-induced neurotoxicity in brain hippocampus tissue possibly via its antioxidant properties and the suppression of iNOS expression and CRH production.

Zinc L-Carnosine Protects CCD-18co Cells from L-Buthionine Sulfoximine-Induced Oxidative Stress via the Induction of Metallothionein and Superoxide Dismutase 1 Expression.

Zinc L-carnosine (ZnC) is the chelate form of zinc and L-carnosine and is one of the zinc supplements available in the market. This study aims to determine the protective effects of ZnC against L-buthionine sulfoximine (BSO)-induced oxidative stress in CCD-18co human normal colon fibroblast cell line. CCD-18co cells were pretreated with ZnC (0-100 µM) for 24 h before the induction of oxidative stress by BSO (1 mM) for another 24 h. Results from this present study demonstrated that ZnC up to the concentration of 100 µM was not cytotoxic to CCD-18co cells. Induction with BSO significantly increased the intracellular reactive oxygen species (ROS) levels and reduced the intracellular glutathione (GSH) levels in CCD-18co cells. Pretreatment with ZnC was able to attenuate the increment in intracellular ROS level in CCD-18co cells significantly in a concentration-dependent manner. However, ZnC did not have any effects on intracellular GSH levels and Nrf2 activation. Mechanistically, pretreatment with ZnC was able to upregulate the expression of metallothionein (MT) and superoxide dismutase 1 (SOD1) in CCD-18co cells. Results from dual-luciferase reporter gene assay reported that ZnC was able to increase the MRE-mediated relative luciferase activities in a concentration-dependent manner, suggesting that the induction of MT expression by ZnC was due to the activation of MTF-1 signaling pathway. Taken together, our current findings suggest that ZnC can protect CCD-18co cells from BSO-induced oxidative stress via the induction of MT and SOD1 expression.