Predictors, Protective Factors, and Adverse Outcomes of Joint Pain among Malaysian Community-Dwelling Older Adults: Findings from the LRGS-TUA Longitudinal Study.

Background: Joint pain has been recognized as one of the major causes of limitations in mobility, functional decline, and consequently declined quality of life in older adults. Hence, this study aimed to identify the predictors, protective factors, and adverse outcomes of joint pain in community-dwelling older adults. Methods: In this Long-term Research Grant Scheme-Towards Useful Ageing (LRGS-TUA) longitudinal study, a total of 1005 older participants aged 60 years and above who were successfully followed up after five years were included in the analysis. The participants self-reported their joint pain status at baseline and during the fifth year. Subsequently, the baseline characteristics were used to predict changes in joint pain status. Adverse outcomes related to joint pain were evaluated based on the participants' joint pain statuses. Results: Results showed that being female, having diabetes mellitus, and higher body mass index were associated with the incidence of joint pain. Meanwhile, increased intake of pantothenic acid and higher levels of blood albumin levels were associated with recovery from joint pain. Participants with persistent joint pain at baseline and follow-up showed higher levels of depression and disability compared to individuals who never experience any joint pain. However, participants who had recovered from joint pain did not differ significantly from those without joint pain at baseline and follow-up in these measures. Conclusions: By identifying the modifiable risk factors, factors associated with recovery, and adverse outcomes related to joint pain, this study adds to current evidence that may contribute to further management strategies for joint pain in older adults.

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.

Genoprotective potential of Macaranga species phytochemical compounds on HT-29 human colorectal adenocarcinoma cell line.

BACKGROUND: The species of genus Macaranga are widely found in Malaysian secondary forests and has been used as an alternative for treating varieties of illness. Studies have shown that the medicinal properties of this genus contain anti-inflammatory, antioxidant, and anti-cancer effects. This study aimed to determine the cytotoxicity of six isolated phytochemicals from Macaranga heynei (M. heynei), Macaranga lowii and Shorea leprosula on HT-29 human colorectal adenocarcinoma cell lines. RESULTS: One out of six isolated phytochemical compounds, identified as "Laevifolin A", showed a cytotoxicity with an IC50 value of 21.2 µM following 48 h treatment as detected using Sulforhodamine B (SRB) assay. Additionally, no induction of apoptosis and oxidative stress were observed on Laevifolin A treated HT-29 cells as determined using Annexin V-FITC/PI assay and dihydroethidine (HE) staining, respectively. Additionally, no damage to the DNA were observed as measured using the Alkaline Comet assay. Further investigation on menadione-induced oxidative DNA damage showed the genoprotective potential of Laevifolin A on HT-29 cells. CONCLUSIONS: In conclusion, this study indicated that only one compound (Laevifolin A) that extracted from M. heynei has the cytotoxicity potential to be developed as an anticancer agent in human colorectal adenocarcinoma. However, besides exhibiting cytotoxic effect, the compound also exhibits genoprotective capability that warrant further investigation.

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.

Genotoxicity and apoptotic effect of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine on malignant melanoma cells, SK-MEL-28.

Complexes of coinage metals can potentially be used as alternatives to platinum-based chemotherapeutic drugs. Silver is a coinage metal that can potentially improve the spectrum of efficacy in various cancers treatment, such as malignant melanoma. Melanoma is the most aggressive form of skin cancer that is often diagnosed in young and middle-aged adults. Silver has high reactivity with skin proteins and can be developed as a malignant melanoma treatment modality. Therefore, this study aims to identify the anti-proliferative and genotoxic effects of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine ligands in the human melanoma SK-MEL-28 cell line. The anti-proliferative effects of a series of silver(I) complex compounds labelled as OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were evaluated on SK-MEL-28 cells by using the Sulforhodamine B assay. Then, DNA damage analysis was performed in a time-dependent manner (30 min, 1 h and 4 h) by using alkaline comet assay to investigate the genotoxicity of OHBT and BrOHMBT at their respective IC50 values. The mode of cell death was studied using Annexin V-FITC/PI flow cytometry assay. Our current findings demonstrated that all silver(I) complex compounds showed good anti-proliferative activity. The IC50 values of OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were 2.38 ± 0.3 µM, 2.70 ± 0.17 µM, 1.34 ± 0.22 µM, 2.82 ± 0.45 µM, and 0.64 ± 0.04 µM respectively. Then, DNA damage analysis showed that OHBT and BrOHMBT could induce DNA strand breaks in a time-dependent manner, with OHBT being more prominent than BrOHMBT. This effect was accompanied by apoptosis induction in SK-MEL-28, as evaluated using Annexin V-FITC/PI assay. In conclusion, silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine exerted anti-proliferative activities by inhibiting cancer cell growth, inducing significant DNA damage and ultimately resulting in apoptosis.

Upregulation of APOC1 Promotes Colorectal Cancer Progression and Serves as a Potential Therapeutic Target Based on Bioinformatics Analysis.

Background: Approximately 10% of cancer patients worldwide have colorectal cancer (CRC), a prevalent gastrointestinal malignancy with substantial mortality and morbidity. The purpose of this work was to investigate the APOC1 gene's expression patterns in the CRC tumor microenvironment and, using the findings from bioinformatics, to assess the biological function of APOC1 in the development of CRC. Methods: The TCGA portal was employed in this investigation to find APOC1 expression in CRC. Its correlation with other genes and clinicopathological data was examined using the UALCAN database. To validate APOC1's cellular location, the Human Protein was employed. In order to forecast the relationship between APOC1 expression and prognosis in CRC patients, the Kaplan-Meier plotter database was used. TISIDB was also employed to evaluate the connection between immune responses and APOC1 expression in CRC. The interactions of APOC1 with other proteins were predicted using STRING. In order to understand the factors that contribute to liver metastasis from CRC, single-cell RNA sequencing (scRNA-seq) was done on one patient who had the disease. This procedure included sampling preoperative blood and the main colorectal cancer tissues, surrounding colorectal cancer normal tissues, liver metastatic cancer tissues, and normal liver tissues. Finally, an in vitro knockdown method was used to assess how APOC1 expression in tumor-associated macrophages (TAMs) affected CRC cancer cell growth and migration. Results: When compared to paracancerous tissues, APOC1 expression was considerably higher in CRC tissues. The clinicopathological stage and the prognosis of CRC patients had a positive correlation with APOC1 upregulation and a negative correlation, respectively. APOC1 proteins are mostly found in cell cytosols where they may interact with APOE, RAB42, and TREM2. APOC1 was also discovered to have a substantial relationship with immunoinhibitors (CD274, IDO1, and IL10) and immunostimulators (PVR, CD86, and ICOS). According to the results of scRNA-seq, we found that TAMs of CRC tissues had considerably more APOC1 than other cell groups. The proliferation and migration of CRC cells were impeded in vitro by APOC1 knockdown in TAMs. Conclusion: Based on scRNA-seq research, the current study shows that APOC1 was overexpressed in TAMs from CRC tissues. By inhibiting APOC1 in TAMs, CRC progression was reduced in vitro, offering a new tactic and giving CRC patients fresh hope.

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.

Higher Lead and Lower Calcium Levels Are Associated with Increased Risk of Mortality in Malaysian Older Population: Findings from the LRGS-TUA Longitudinal Study.

The main objective of this study is to determine the association of various trace elements' status with the 5-year mortality rate among community-dwelling older adults in Malaysia. This study was part of the Long-term Research Grant Scheme­Towards Useful Ageing (LRGS-TUA). The participants were followed up for five years, and their mortality status was identified through the Mortality Data Matching Service provided by the National Registration Department, Malaysia. Of the 303 participants included in this study, 34 (11.2%) participants had died within five years after baseline data collection. As compared to the survivors, participants who died earlier were more likely (p < 0.05) to be men, smokers, have a lower intake of total dietary fiber and molybdenum, higher intake of manganese, lower zinc levels in toenail samples, lower calcium and higher lead levels in hair samples during baseline. Following the multivariate Cox proportional hazard analysis, lower total dietary fiber intake (HR: 0.681; 0.532−0.871), lower calcium (HR: 0.999; 95% CI: 0.999−1.000) and higher lead (HR: 1.309; 95% CI: 1.061−1.616) levels in hair samples appeared as the predictors of mortality. In conclusion, higher lead and lower calcium levels are associated with higher risk of mortality among community-dwelling older adults in Malaysia. Our current findings provide a better understanding of how the trace elements' status may affect older populations' well-being and mortality rate.

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.

Multidimensional Risk Factors of Age-Related Hearing Loss Among Malaysian Community-Dwelling Older Adults.

PURPOSE: This study evaluates the prevalence of and the multidimensional risk factors associated with age-related hearing loss (ARHL) among community-dwelling older adults in Malaysia. PATIENTS AND METHODS: A total of 253 participants aged 60 years and above participated in this cross-sectional study. The participants were subjected to pure tone audiometric assessment. The hearing threshold was calculated for the better ear and classified into pure-tone average (PTA) for the octave frequencies from 0.5 to 4 kHz and high-frequency pure-tone average (HFA) for the octave from 2 to 8kHz. Then, the risk factors associated with PTA hearing loss (HL) and HFAHL were identified by using multivariate logistic regression analysis. RESULTS: The prevalence of ARHL based on PTA and HFA among the community-dwelling older adults was 75.5% and 83.0%, respectively. Following multifactorial adjustments, being older (OR: 1.239; 95% CI: 1.062-1.445), having higher waist circumference (OR: 1.158; 95% CI: 1.015-1.322), lower intake of niacin (OR: 0.909; 95% CI: 0.831-0.988) and potassium (OR: 0.998; 95% CI: 0.996-1.000), and scoring lower in RAVLT T5 (OR: 0.905; 95% CI: 0.838-0.978) were identified as the risk factors of PTAHL. Meanwhile, being older (OR: 1.117; 95% CI: 1.003-1.244), higher intake of carbohydrate (OR: 1.018; 95% CI: 1.006-1.030), lower intake of potassium (OR: 0.998; 95% CI: 0.997-0.999), and lower scores on the RAVLT T5 (OR: 0.922; 95% CI: 0.874-0.973) were associated with increased risk of having HFAHL. CONCLUSION: Increasing age, having higher waist circumference, lower intake of niacin and potassium, higher intake of carbohydrates and having lower RAVLT T5 score were associated with increased risk of ARHL. Modifying these risk factors may be beneficial in preventive and management strategies of ARHL among older persons.

Higher levels of lead and aluminium are associated with increased risk of falls among community-dwelling older adults: An 18-month follow-up study.

AIM: The present study aims to determine the association of trace elements and oxidative and DNA damage biomarkers with fall incidence among community-dwelling older adults. METHODS: This study is part of the Long-term Research Grant Scheme - Towards Useful Ageing cohort study in Malaysia. Of a total of 174 participants with complete trace elements and oxidative and DNA damage data during baseline, only 147 (84.5%) were successfully followed up after 18 months. Participants who experienced any fall events in the previous 18 months during the follow-up were categorized as fallers. RESULTS: Thirty participants (20.4%) reported at least one fall in the previous 18 months. The mean concentrations of aluminium, lead and zinc were significantly higher (P < 0.05) in fallers than non-fallers. However, in comparison with the non-faller group, the percentage of DNA in tail (11.43 ± 4.10% vs. 13.22 ± 5.24%) and tail moment (1.19 ± 0.54 AU vs. 1.59 ± 0.78 AU) was significantly (P < 0.05) lower in the faller group. No significant difference in serum superoxide dismutase activities and malondialdehyde level was observed between non-fallers and fallers. Following multifactorial adjustments, higher aluminium (odds ratio [OR]: 1.007; 95% confidence interval [CI]: 1.002-1.011) and lead (OR: 1.162; 95% CI: 1.010-1.336) levels and lower tail moment scores (OR: 0.313; 95% CI: 0.138-0.709) appeared significant in the final hierarchical binary logistic regression model. CONCLUSIONS: Higher levels of lead and aluminium were associated with increased risk of falls among community-dwelling older adults. Geriatr Gerontol Int 2021; 21: 1026-1032.

A 16-Week Home-Based Progressive Resistance Tube Training Among Older Adults With Type-2 Diabetes Mellitus: Effect on Glycemic Control.

Research has proven that aerobic exercise improves glucose homeostasis among patients with type 2 diabetes mellitus (T2DM). Elastic resistance (tube or band) is suggested as a good alternative for home-based strength training among older adults including those with T2DM due to its low cost, simplicity, portability, and versatility. This study aimed to measure the effects of 16-week home-based progressive resistance training (PRT), using a resistance tube on glucose homeostasis and cardiovascular risk factors among older adults with T2DM. A total of 70 participants aged 61.68 (5.50) years with T2DM were assigned to the intervention (n = 35) and control (n = 35) groups in this quasi-experimental trial. The intervention group underwent 16 weeks of home-based PRT using a resistance tube. Significant improvements in HbA1c (-1.34% point, p < 0.001), fasting blood glucose (-1.30 mmol/L, p < 0.001), and systolic blood pressure (-1.42 mmHg, p < 0.05) were observed after 16 weeks of intervention. However, no significant changes were observed in lipid profile, diastolic blood pressure, resting heart rate, and ankle-brachial index. The finding suggests that 16 weeks of home-based PRT using a resistance tube has the potential to improve glycemic control and reduce systolic blood pressure among older adults with T2DM and caused no adverse events.

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.

Incidence and multidimensional predictors of occasional and recurrent falls among Malaysian community-dwelling older persons.

BACKGROUND: Falls incidence rate and comprehensive data on factors that predict occasional and repeated falls from large population-based studies are scarce. In this study, we aimed to determine the incidence of falls and identify predictors of occasional and recurrent falls. This was done in the social, medical, physical, nutritional, biochemical, cognitive dimensions among community-dwelling older Malaysians. METHODS: Data from 1,763 Malaysian community-dwelling older persons aged ≥ 60 years were obtained from the LRGS-TUA longitudinal study. Participants were categorized into three groups according to the presence of a single fall (occasional fallers), ≥two falls (recurrent fallers), or absence of falls (non-fallers) at an 18-month follow-up. RESULTS: Three hundred and nine (17.53 %) participants reported fall occurrences at an 18-month follow-up, of whom 85 (27.51 %) had two or more falls. The incidence rate for occasional and recurrent falls was 8.47 and 3.21 per 100 person-years, respectively. Following multifactorial adjustments, being female (OR: 1.57; 95 % CI: 1.04-2.36), being single (OR: 5.31; 95 % CI: 3.36-37.48), having history of fall (OR: 1.86; 95 % CI: 1.19-2.92) higher depression scale score (OR: 1.10; 95 % CI: 1.02-1.20), lower hemoglobin levels (OR: 0.90; 95 % CI: 0.81-1.00) and lower chair stand test score (OR: 0.93; 95 % CI: 0.87-1.00) remained independent predictors of occasional falls. While, having history of falls (OR: 2.74; 95 % CI: 1.45-5.19), being a stroke survivor (OR: 8.57; 95 % CI: 2.12-34.65), higher percentage of body fat (OR: 1.04; 95 % CI: 1.01-1.08) and lower chair stand test score (OR: 0.87; 95 % CI: 0.77-0.97) appeared as recurrent falls predictors. CONCLUSIONS: Having history of falls and lower muscle strength were predictors for both occasional and recurrent falls among Malaysian community-dwelling older persons. Modifying these predictors may be beneficial in falls prevention and management strategies among older persons.

Intermittent Fasting Enhanced the Cognitive Function in Older Adults with Mild Cognitive Impairment by Inducing Biochemical and Metabolic changes: A 3-Year Progressive Study.

Intermittent fasting (IF) refers to various dietary regimens that cycle between a period of non-fasting and a period of total fasting. This study aimed to determine the effects of IF on cognitive function among elderly individuals who practice IF who have mild cognitive impairment (MCI). A total of 99 elderly subjects with MCI of Malay ethnicity without any terminal illness were recruited from a larger cohort study, LRGS TUA. The subjects were divided into three groups, comprising those who were regularly practicing IF (r-IF), irregularly practicing IF (i-IF), and non-fasters (n-IF). Upon 36 months of follow-up, more MCI subjects in the r-IF group reverted to successful aging with no cognitive impairment and diseases (24.3%) compared to those in i-IF (14.2%) and n-IF groups (3.7%). The r-IF group's subjects exhibited significant increment in superoxide dismutase (SOD) activity and reduction in body weight, levels of insulin, fasting blood glucose, malondialdehyde (MDA), C-reactive protein (CRP), and DNA damage. Moreover, metabolomics analysis showed that IF may modulate cognitive function via various metabolite pathways, including the synthesis and degradation of ketone bodies, butanoate metabolism, pyruvate metabolism, and glycolysis and gluconeogenesis pathways. Overall, the MCI-afflicted older adults who practiced IF regularly had better cognitive scores and reverted to better cognitive function at 36 months follow-up.

Protective effects of zinc L-carnosine against hydrogen peroxide-induced DNA damage and micronucleus formation in CCD-18co human colon fibroblast cells.

Zinc L-carnosine (ZnC) is a chelated compound of zinc and L-carnosine. The present study aims to determine the protective effects of ZnC against hydrogen peroxide (H2O2)-induced oxidative stress and genomic damage in CCD-18co human normal colon fibroblast cells. Generally, cells were pretreated with ZnC (0-100 µM) for 24 h before challenged with 20 µM of H2O2 for 1 h to induce oxidative damage. Results showed that pretreatment with ZnC was able to reduce the intracellular ROS level in CCD-18co cells after being challenged with H2O2. Moreover, pretreatment with ZnC demonstrated protection from H2O2-induced DNA strand breaks and micronucleus formation. Our current findings revealed that pretreatment with ZnC could induce the activation of MTF-1 signaling pathway and expression of metallothionein (MT) in a dose-dependent manner. However, ZnC did not have any effects on Nrf2 signaling pathway and the expression of glutathione, superoxide dismutase 1, and glutamate-cysteine ligase catalytic subunit (GCLC). Furthermore, pretreatment with ZnC did not induce the expression of OGG1 and PARP-1 in CCD-18co cells, suggesting that these two DNA repairing enzymes are not related to the genoprotective effects of ZnC. Since the expression of MT has been demonstrated to protect cells from oxidative DNA damage induced by various genotoxic agents, the genoprotective effects of ZnC might be due to the ability of ZnC to induce the expression of MT. In conclusion, ZnC pretreatment was able to protect CCD-18co cells from H2O2-induced genomic damage via the activation of the MTF-1 signalling pathway and the induction of MT expression.

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.