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Fulltext Curcumin piperidone derivatives induce anti-proliferative and anti-migratory effects in LN-18 human glioblastoma cells

Razali NSC, Lam KW, Rajab NF, A Jamal AR, Kamaluddin NF, Chan KM

Sci Rep, 2022 07 30;12(1):13131.
PMID: 35907913 DOI: 10.1038/s41598-022-16274-4

Curcumin has demonstrated potential cytotoxicity across various cell lines despite its poor bioavailability and rapid metabolism. Therefore, our group have synthesized curcuminoid analogues with piperidone derivatives, FLDP-5 and FLDP-8 to overcome these limitations. In this study, the analogues were assessed on LN-18 human glioblastoma cells in comparison to curcumin. Results from cytotoxicity assessment showed that FLDP-5 and FLDP-8 curcuminoid analogues caused death in LN-18 cells in a concentration-dependent manner after 24-h treatment with much lower IC50 values of 2.5 µM and 4 µM respectively, which were more potent compared to curcumin with IC50 of 31 µM. Moreover, a significant increase (p
Fulltext Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells

Razali NSC, Lam KW, Rajab NF, Jamal ARA, Kamaludin NF, Chan KM

Genes Environ, 2024 Feb 01;46(1):4.
PMID: 38303058 DOI: 10.1186/s41021-023-00297-y

BACKGROUND: Previously, we have reported on the two curcuminoid analogues with piperidone derivatives, namely FLDP-5 and FLDP-8 have more potent anti-proliferative and anti-migration effects than curcumin. In this study, we further investigated the mode of cell death and the mechanism involved in the cell death process induced by these analogues on human glioblastoma LN-18 cells.
RESULTS: The FLDP-5 and FLDP-8 curcuminoid analogues induced LN-18 cell death through apoptosis in a concentration-dependent manner following 24 h of treatment. These analogues induced apoptosis in LN-18 cells through significant loss of mitochondrial mass and mitochondrial membrane potential (MMP) as early as 1-hour of treatment. Interestingly, N-acetyl-l-cysteine (NAC) pretreatment did not abolish the apoptosis induced by these analogues, further confirming the cell death process is independent of ROS. However, the apoptosis induced by the analogues is caspases-dependent, whereby pan-caspase pretreatment inhibited the curcuminoid analogues-induced apoptosis. The apoptotic cell death progressed with the activation of both caspase-8 and caspase-9, which eventually led to the activation of caspase-3, as confirmed by immunoblotting. Moreover, the existing over-expression of miRNA-21 in LN-18 cells was suppressed following treatment with both analogues, which suggested the down-regulation of the miRNA-21 facilitates the cell death process.
CONCLUSION: The FLDP-5 and FLDP-8 curcuminoid analogues downregulate the miRNA-21 expression and induce extrinsic and intrinsic apoptotic pathways in LN-18 cells.
Fulltext Cognitive frailty is a robust predictor of falls, injuries, and disability among community-dwelling older adults

Rivan NFM, Singh DKA, Shahar S, Wen GJ, Rajab NF, Din NC, et al.

BMC Geriatr, 2021 10 25;21(1):593.
PMID: 34696720 DOI: 10.1186/s12877-021-02525-y

BACKGROUND: Cognitive frailty, a combination of physical frailty and cognitive impairment, is associated with functional decline in older adults. However, there is limited information if cognitive frailty predicts the incidence of falls, injuries, and disability. In this study, we aimed to determine the ability of cognitive frailty in predicting the incidence of falls, injuries and disability among multi-ethnic older adults in Malaysia at 5 years follow-up.
METHODS: In this prospective cohort study, a total of 400 participants aged 60 years and above were successfully followed up at 5 years. Participants' socio-demographic, medical history, psycho-social, physical, cognitive and dietary intake information was obtained. Cognitive frailty was defined as comorbid physical frailty (> 1 Fried criteria) and mild cognitive impairment (Petersen criteria). Univariate analysis was performed for all variables, followed by hierarchical binary logistic regression (BLR) analysis to identify the ability of CF in predicting the incidence of falls, injuries, and disability. The significant value was set at p
The effects of polyphenols-rich tropical fruit juice on cognitive function and metabolomics profile - a randomized controlled trial in middle-aged women

Rosli H, Shahar S, Rajab NF, Che Din N, Haron H

Nutr Neurosci, 2021 Mar 05.
PMID: 33666540 DOI: 10.1080/1028415X.2021.1880312

Objectives: Polyphenols, particularly anthocyanins, have received attention in improving health issues during old age, including decline in cognitive function and other health parameters. We aimed to determine the effects of polyphenols-rich tropical fruit TP 3-in-1™ juice towards improving cognitive function, oxidative stress and metabolomics profiles among middle-aged women.Methods: This clinical trial involved 31 subjects with signs of poor cognitive function, as assessed using the Rey Auditory Verbal Learning Test (RAVLT). They were randomized to receive either TP 3-in-1™ juice (n = 16) or placebo (n = 15). Study subjects consumed 500 ml of beverages for three times per day, three days per week, for a period of ten weeks. Juice supplementation provided 9135 mg GAE of total phenolic content and 194.1 mg cyanidin-3-glucoside of total anthocyanin monomer.Results: There was a significant interaction effects on RAVLT immediate recall (p
Fulltext Prevalence of Poor Mental Health and Cognitive Status among Middle-Aged Adults and Its Predictors in Relation to Polyphenols Intake

Rosli H, Shahar S, Din NC, Haron H, Rajab NF

Malays J Med Sci, 2019 May;26(3):72-89.
PMID: 31303852 MyJurnal DOI: 10.21315/mjms2019.26.3.6

Background: Decline in mental health and cognitive status starts to show its sign during middle-age and is affected by dietary factors, namely the polyphenols intake. Polyphenols have received attention in improving health issues related to aging, including decline in mental health and cognitive. The aim of this study is to determine the prevalence of poor mental health and cognitive status among middle-aged adults and its predictors in relation to polyphenols intake.
Methods: Subjects' food intakes were calculated by using dietary history questionnaire and food frequency questionnaire for polyphenols. The subjects' mental health and cognitive status were measured by general health questionnaire-28 (GHQ-28) and Rey's auditory verbal learning test (RAVLT).
Results: More than 40% of middle-aged adults were identified as having signs of poor mental health. A total of 67.9% of the subjects had poor cognitive status according to RAVLT immediate recall. Hierarchical binary logistic regression indicated that fat intake was associated with somatic symptoms for both men [adjusted odds ratio (AOR) = 1.04; P < 0.05] and women (AOR = 1.06; P < 0.05). Intake of lignan (AOR = 1.071; P < 0.05) was associated with better RAVLT immediate recall among women. Additionally, high cholesterol (AOR = 3.14; P < 0.05) was associated with poor score of RAVLT delayed recall for women.
Conclusions: Early detection of poor mental health and cognitive is crucial to prevent Alzheimer's disease in old age.
Fulltext Serum Metabolomics Profiling of Commercially Mixed Functional Foods-Effects in Beta-Amyloid Induced Rats Measured Using 1H NMR Spectroscopy

Rosli NHM, Yahya HM, Ibrahim FW, Shahar S, Ismail IS, Azam AA, et al.

Nutrients, 2020 Dec 12;12(12).
PMID: 33322743 DOI: 10.3390/nu12123812

Functional foods such as pomegranate, dates and honey were shown by various previous studies to individually have a neuroprotective effect, especially in neurodegenerative disease such as Alzheimer's disease (AD). In this novel and original study, an 1H NMR spectroscopy tool was used to identify the metabolic neuroprotective mechanism of commercially mixed functional foods (MFF) consisting of pomegranate, dates and honey, in rats injected with amyloid-beta 1-42 (Aβ-42). Forty-five male albino Wistar rats were randomly divided into five groups: NC (0.9% normal saline treatment + phosphate buffer solution (PBS) solution injection), Abeta (0.9% normal saline treatment + 0.2 µg/µL Aβ-42 injection), MFF (4 mL/kg MFF treatment + PBS solution injection), Abeta-MFF (4 mL/kg MFF treatment + 0.2 µg/µL Aβ-42 injection) and Abeta-NAC (150 mg/kg N-acetylcysteine + 0.2 µg/µL Aβ-42 injection). Based on the results, the MFF and NAC treatment improved the spatial memory and learning using Y-maze. In the metabolic analysis, a total of 12 metabolites were identified, for which levels changed significantly among the treatment groups. Systematic metabolic pathway analysis found that the MFF and NAC treatments provided a neuroprotective effect in Aβ-42 injected rats by improving the acid amino and energy metabolisms. Overall, this finding showed that MFF might serve as a potential neuroprotective functional food for the prevention of AD.
3,5-dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells

Roslie H, Chan KM, Rajab NF, Velu SS, Kadir SA, Bunyamin I, et al.

J Toxicol Sci, 2012 Feb;37(1):13-21.
PMID: 22293408

A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy- and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4'-hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4'-hydroxystilbene (28) with IC(50)s of 78 µM, 38 µM, 67 µM and 19.5 µM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure-activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9.
Electrochemical DNA biosensor for potential carcinogen detection in food sample

Sani NDM, Heng LY, Marugan RSPM, Rajab NF

Food Chem, 2018 Dec 15;269:503-510.
PMID: 30100466 DOI: 10.1016/j.foodchem.2018.07.035

The presence of carcinogens in food is a major food safety concern. A nanocomposite-based electrochemical DNA biosensor was constructed for potential carcinogen detection in food samples by immobilizing amine terminated single stranded DNA onto silica nanospheres deposited onto a screen-printed electrode modified using gold nanoparticles. The effect of three different DNA sequences: 15-base guanine, 24-base guanine and 24-base adenine-thymine rich DNA on carcinogen (formaldehyde and acrylamide) detection was evaluated. The competitive binding of the DNA with the carcinogen and electroactive indicator, Methylene blue (MB) was measured using differential pulse voltammetry. Optimization studies were conducted for MB concentration and accumulation time, DNA concentration, buffer concentration, pH and ionic strength. Overall, the 24-base guanine rich DNA yielded the best results with a detection limit of 0.0001 ppm, linear range between 0.0001 ppm and 0.1 ppm and reproducibility below 5% R.S.D. Finally, the results obtained using the biosensor were validated using Ames test.
Impact of diabetes mellitus on osteoarthritis: a scoping review on biomarkers

Seow SR, Mat S, Ahmad Azam A, Rajab NF, Safinar Ismail I, Singh DKA, et al.

Expert Rev Mol Med, 2024 Apr 12;26:e8.
PMID: 38606593 DOI: 10.1017/erm.2024.7

Osteoarthritis (OA) commonly affects the knee and hip joints and accounts for 19.3% of disability-adjusted life years and years lived with disability worldwide (Refs , ). Early management is important in order to avoid disability uphold quality of life (Ref. ). However, a lack of awareness of subclinical and early symptomatic stages of OA often hampers early management (Ref. ). Moreover, late diagnosis of OA among those with severe disease, at a stage when OA management becomes more complicated is common (Refs , , , ). Established risk factors for the development and progression of OA include increasing age, female, history of trauma and obesity (Ref. ). Recent studies have also drawn a link between OA and metabolic syndrome, which is characterized by insulin resistance, dyslipidaemia and hypertension (Refs , ).
Fulltext Approaches in methodology for population-based longitudinal study on neuroprotective model for healthy longevity (TUA) among Malaysian Older Adults

Shahar S, Omar A, Vanoh D, Hamid TA, Mukari SZ, Din NC, et al.

Aging Clin Exp Res, 2016 Dec;28(6):1089-1104.
PMID: 26670602 DOI: 10.1007/s40520-015-0511-4

A number of longitudinal studies on aging have been designed to determine the predictors of healthy longevity, including the neuroprotective factors, however, relatively few studies included a wide range of factors and highlighted the challenges faced during data collection. Thus, the longitudinal study on neuroprotective model for healthy longevity (LRGS TUA) has been designed to prospectively investigate the magnitude of cognitive decline and its risk factors through a comprehensive multidimensional assessment comprising of biophysical health, auditory and visual function, nutrition and dietary pattern and psychosocial aspects. At baseline, subjects were interviewed for their status on sociodemographic, health, neuropsychological test, psychosocial and dietary intake. Subjects were also measured for anthropometric and physical function and fitness. Biospecimens including blood, buccal swap, hair and toenail were collected, processed and stored. A subsample was assessed for sensory function, i.e., vision and auditory. During follow-up, at 18 and 36 months, most of the measurements, along with morbidity and mortality outcomes will be collected. The description of mild cognitive impairment, successful aging and usual aging process is presented here. A total 2322 respondents were recruited in the data analysis at baseline. Most of the respondents were categorized as experiencing usual aging (73 %), followed by successful aging (11 %) and mild cognitive impairment (16 %). The LRGS TUA study is the most comprehensive longitudinal study on aging in Malaysia, and will contribute to the understanding of the aging process and factors associated with healthy aging and mental well-being of a multiethnic population in Malaysia.
Roles of diet, lifetime physical activity and oxidative DNA damage in the occurrence of prostate cancer among men in Klang Valley, Malaysia

Shahar S, Shafurah S, Hasan Shaari NS, Rajikan R, Rajab NF, Golkhalkhali B, et al.

Asian Pac J Cancer Prev, 2011;12(3):605-11.
PMID: 21627352

BACKGROUND: There is a paucity of information on risk factors of prostate cancer, especially those related to dietary and lifestyle among Asian populations.
OBJECTIVE: This study aimed to determine the relationship between dietary intake (macronutrients, fruits, vegetables and lycopene), lifetime physical activity and oxidative DNA damage with prostate cancer.
DESIGN: A case control study was carried out among 105 subjects (case n=35, control n=70), matched for age and ethnicity. Data on sociodemographic, medical, dietary intake, consumption of lycopene rich food and lifetime physical activity were obtained through an interview based questionnaire. Anthropometric measurements including weight, height and waist hip circumferences were also carried out on subjects. A total of 3 mL fasting venous blood was drawn to assess lymphocyte oxidative DNA damage using the alkaline comet assay.
RESULTS: Cases had a significantly higher intake of fat (27.7 ± 5.5%) as compared to controls (25.1 ± 5.9%) (p < 0.05). Mean intakes of fruits and vegetables (3.11 ± 1.01 servings/d)(p < 0.05), fruits (1.23 ± 0.59 servings/d) (p<0.05) and vegetables (1.97 ± 0.94 servings/d) were higher in controls than cases (2.53 ± 1.01, 0.91 ∓ 0.69, 1.62 ± 0.82 servings/d). A total of 71% of cases did not met the recommendation of a minimum of three servings of fruits and vegetables daily, as compared to 34% of controls (p < 0.05) (adjusted OR 6.52 (95% CI 2.3-17.8)) (p < 0.05). Estimated lycopene intake among cases (2,339 ∓ 1,312 mcg/d) were lower than controls (3881 ∓ 3120 mcg/d) (p< 0.01). Estimated lycopene intake of less than 2,498 mcg/day (50th percentile) increased risk of prostate cancer by double [Adjusted OR 2.5 (95%CI 0.99-6.31)]. Intake of tomatoes, watermelon, guava, pomelo, papaya, mango, oranges, dragon fruit, carrot, tomato sauce and barbeque sauce were higher in controls compared to cases. Intake of tomato sauce of more than 2.24 g/d (25th percentile), papaya more than 22.7 g/d (50th percentile) and oranges more than 19.1g/h (50th percentile) reduced prostate cancer risk by 7.4 (Adjusted OR 7.4 (95% CI 1.17-46.8)), 2.7 (adjusted OR 2.75 (95% CI 1.03-7.39)) and 2.6 times (adjusted OR = 2.6 (95% CI=1.01-6.67)), respectively (p < 0.05 for all parameters). No oxidative damage was observed among subjects. Past history of not engaging with any physical activities at the age of 45 to 54 years old increased risk of prostate cancer by approximately three folds (Adjusted OR 2.9(95% CI = 0.8-10.8)) (p < 0.05). In conclusion, low fat diet, high intake of fruits, vegetables and lycopene rich foods and being physical active at middle age were found to be protective. Thus, it is essential for Malaysian men to consume adequate fruits and vegetables, reduce fat intake and engage in physical activity in order to reduce prostate cancer risk.
Toxicological evaluation of some Malaysian locally processed raw food products

Sharif R, Ghazali AR, Rajab NF, Haron H, Osman F

Food Chem Toxicol, 2008 Jan;46(1):368-74.
PMID: 17900779

Malaysian locally processed raw food products are widely used as main ingredients in local cooking. Previous studies showed that these food products have a positive correlation with the incidence of cancer. The cytotoxicity effect was evaluated using MTT assay (3-(4,5-dimetil-2-thiazolil)-2,5-diphenyl-2H-tetrazolium bromide) against Chang liver cells at 2000 microg/ml following 72 h incubation. Findings showed all methanol extracts caused a tremendous drop in the percentage of cell viability at 2000 microg/ml (shrimp paste - 41.69+/-3.36%, salted fish - 37.2+/-1.06%, dried shrimp - 40.32+/-1.8%, p<0.05). To detect DNA damage in a single cell, alkaline Comet Assay was used. None of the extracts caused DNA damage to the Chang liver cells at 62.5 microg/ml following 24 h incubation, as compared to the positive control, hydrogen peroxide (tail moment - 9.50+/-1.50; tail intensity - 30.50+/-2.50). Proximate analysis which was used for the evaluation of macronutrients in food showed that shrimp paste did not comply with the protein requirement (<25%) as in Food Act 1983. Salt was found in every sample with the highest percentage being detected in shrimp paste which exceeded 20%. Following heavy metal analysis (arsenic, cadmium, lead and mercury), arsenic was found in every sample with dried shrimps showing the highest value as compared to the other samples (6.16 mg/kg). In conclusion, several food extracts showed cytotoxic effect but did not cause DNA damage against Chang liver cells. Salt was found as the main additive and arsenic was present in every sample, which could be the probable cause of the toxicity effects observed.
Dietary Pattern, Genomic Stability and Relative Cancer Risk in Asian Food Landscape

Sharif R, Shahar S, Rajab NF, Fenech M

Nutr Cancer, 2021 Jul 20.
PMID: 34282666 DOI: 10.1080/01635581.2021.1952627

The incidence of cancer globally is increasing, partly due to lifestyle factors. Despite a better understanding of cancer biology and advancement in cancer management and therapies, current strategies in cancer treatment remain costly and cause socioeconomic burden especially in Asian countries. Hence, instead of putting more efforts in searches for new cancer cures, attention has now shifted to understanding how to mitigate cancer risk by modulating lifestyle factors. It has been established that carcinogenesis is multifactorial, and the important detrimental role of oxidative stress, chronic inflammation, and genomic instability is evident. To date, there is no study linking dietary pattern and genomic stability in cancer risk in the Asian food landscape. Thus, this present review article discusses recent literature on dietary pattern and genomic stability and its relationship with cancer risk in Asia.
Mutagenic and clastogenic characterization of poststerilized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer biosynthesized by Delftia acidovorans

Siew EL, Rajab NF, Osman AB, Sudesh K, Inayat-Hussain SH

J Biomed Mater Res A, 2009 Dec;91(3):786-94.
PMID: 19051306 DOI: 10.1002/jbm.a.32290

Polyhydroxyalkanoates (PHA) are naturally occurring biopolyesters that have great potential in the medical field. However, the leachables resulting from sterilization process of the biomaterials may exert toxic effect including genetic damage. Here, we demonstrate that although gamma-irradiation of poly(3-hydroxybutyrate-co-50 mol % 4-hydroxybutyrate) [P(3HB-co-4HB)] did not cause any change in the morphology by scanning electron microscopy, there was a significant degradation of this copolymer where the molecular weight was reduced by 37% after sterilization indicating the generation of leachables. Therefore, further investigation on the ability of the extract of this poststerilized copolymer to induce mutagenic effect was performed using Ames test (S. typhimurium strains TA1535 and TA1537) and umu test (S. typhimurium strain TA1535/pSK1002). Additionally, the capability of the extract to induce clastogenic effect was determined using Chinese hamster lung V79 fibroblast cells. Our results showed that with and without the presence of S9 metabolic activation, no mutagenic effects were observed in both Ames and umu tests when treated with P(3HB-co-4HB) extract. Similarly, treatment of P(3HB-co-4HB) extract in V79 fibroblast cells showed no significant production of micronuclei when compared with the positive control (Mitomycin C). Together, these results indicate that leachables of poststerilized P(3HB-co-4HB) cause no mutagenic and clastogenic effects.
In vitro biocompatibility evaluation of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer in fibroblast cells

Siew EL, Rajab NF, Osman AB, Sudesh K, Inayat-Hussain SH

J Biomed Mater Res A, 2007 May;81(2):317-25.
PMID: 17120221

Among the various biomaterials available for tissue engineering and therapeutic applications, microbial polyhydroxyalkanoates offer the most diverse range of thermal and mechanical properties. In this study, the biocompatibility of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB); containing 50 mol % of 4-hydroxybutyrate] copolymer produced by Delftia acidovorans was evaluated. The cytotoxicity, mode of cell death, and genotoxicity of P(3HB-co-4HB) extract against V79 and L929 fibroblast cells were assessed using MTT assay, acridine orange/propidium iodide staining, and alkaline comet assay, respectively. Our results demonstrate that P(3HB-co-4HB) treated on both cell lines were comparable with clinically-used Polyglactin 910, where more than 60% of viable cells were observed following 72-h treatment at 200 mg/mL. Further morphological investigation on the mode of cell death showed an increase in apoptotic cells in a time-dependent manner in both cell lines. On the other hand, P(3HB-co-4HB) at 200 mg/mL showed no genotoxic effects as determined by alkaline comet assay following 72-h treatment. In conclusion, our study indicated that P(3HB-co-4HB) compounds showed good biocompatibility in fibroblast cells suggesting that it has potential to be used for future medical applications.
Fulltext In vitro toxicological assessment of gadolinium (III) chloride in V79-4 fibroblasts

Siew EL, Farris AF, Rashid N, Chan KM, Rajab NF

Genes Environ, 2020;42:22.
PMID: 32537035 DOI: 10.1186/s41021-020-00161-3

Background: Rare earth minerals of the lanthanide series are widely used in the field of medical and clinical application. Gadolinium (Gd), the most preferred rare earth mineral is frequently used as magnets, superconductors and magnetic resonance imaging (MRI) contrast agent. Increasing production of gadolinium waste, known potent toxicity of this element and lack of information on its Material Safety Data Sheet (MSDS) prompts health risk assessment on gadolinium. In this study, cytotoxicity and genotoxicity of Gadolinium (III) chloride (GdCl3) were investigated using MTT assay, Alkaline Comet assay and Micronucleus assay, respectively.
Results: Our results demonstrated that the viability of GdCl3 treated V79-4 cells was significantly (p 0.05) DNA damage both in the presence and absence of metabolic activation. However, it induced significant (p
Fulltext Toxic effects of Litsea elliptica Blume essential oil on red blood cells of Sprague-Dawley rats

Taib IS, Budin SB, Siti Nor Ain SM, Mohamed J, Louis SR, Das S, et al.

J Zhejiang Univ Sci B, 2009 Nov;10(11):813-9.
PMID: 19882755 DOI: 10.1631/jzus.B0920199

Litsea elliptica Blume leaves have been traditionally used as medicinal herbs because of its antimutagenicity, chemopreventative and insecticidal properties. In this study, the toxic effects of L. elliptica essential oil against Sprague-Dawley rat's red blood cells (RBCs) were evaluated. L. elliptica essential oil was given by oral gavage 5 times per week for 3 treated groups in the doses of 125, 250, and 500 mg/(kg body weight), respectively, and the control group received distilled water. Full blood count, RBC osmotic fragility, RBC morphological changes, and RBC membrane lipid were analyzed 28 d after the treatment. Although L. elliptica essential oil administration had significantly different effects on hemoglobin (Hb), mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), and mean cell hemoglobin (MCH) in the experimental groups as compared to the control group (P<0.05), the values were still within the normal range. L. elliptica induced morphological changes of RBC into the form of echinocyte. The percentage of echinocyte increased significantly among the treated groups in a dose-response manner (P<0.001). The concentrations of RBC membrane phospholipids and cholesterol of all treated groups were significantly lower than those of control group (P<0.001). However, the RBC membrane osmotic fragility and total proteins of RBC membrane findings did not differ significantly between control and treated groups (P>0.05). It is concluded that structural changes in the RBC membrane due to L. elliptica essential oil administration did not cause severe membrane damage.
Fulltext Efficacy of zinc carnosine in the treatment of colorectal cancer and its potential in combination with immunotherapy in vivo

Tang W, Liu H, Li X, Ooi TC, Rajab NF, Cao H, et al.

Aging (Albany NY), 2022 Nov 14;14(21):8688-8699.
PMID: 36375474 DOI: 10.18632/aging.204380

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

Tang W, Liu H, Li X, Ooi TC, Rajab NF, Cao H, et al.

J Oncol, 2023;2023:2611105.
PMID: 36908705 DOI: 10.1155/2023/2611105

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.
Improvement of metabolic parameters in healthy older adult men following a fasting calorie restriction intervention

Teng NI, Shahar S, Rajab NF, Manaf ZA, Johari MH, Ngah WZ

Aging Male, 2013 Dec;16(4):177-83.
PMID: 24044618 DOI: 10.3109/13685538.2013.832191

Calorie restriction and intermittent fasting are two dietary interventions that can improve aging. Religious fasting also suggested having similar benefit; however, such studies are still scarce. Thus, this study aimed to determine the effect of fasting calorie restriction (FCR) on metabolic parameters and DNA damage among healthy older adult men.

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