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Fulltext Apocynin and catalase prevent hypertension and kidney injury in Cyclosporine A-induced nephrotoxicity in rats

Tan YC, Abdul Sattar M, Ahmeda AF, Abdul Karim Khan N, Murugaiyah V, Ahmad A, et al.

PLoS One, 2020;15(4):e0231472.
PMID: 32298299 DOI: 10.1371/journal.pone.0231472

Oxidative stress is involved in the pathogenesis of a number of diseases including hypertension and renal failure. There is enhanced expression of nicotinamide adenine dinucleotide (NADPH oxidase) and therefore production of hydrogen peroxide (H2O2) during renal disease progression. This study investigated the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on Cyclosporine A (CsA) nephrotoxicity in Wistar-Kyoto rats. Rats received CsA (25mg/kg/day via gavage) and were assigned to vehicle, apocynin (2.5mmol/L p.o.), catalase (10,000U/kg/day i.p.) or apocynin plus catalase for 14 days. Renal functional and hemodynamic parameters were measured every week, and kidneys were harvested at the end of the study for histological and NADPH oxidase 4 (NOX4) assessment. Oxidative stress markers and blood urea nitrogen (BUN) were measured. CsA rats had higher plasma malondialdehyde (by 340%) and BUN (by 125%), but lower superoxide dismutase and total antioxidant capacity (by 40%, all P<0.05) compared to control. CsA increased blood pressure (by 46mmHg) and decreased creatinine clearance (by 49%, all P<0.05). Treatment of CsA rats with apocynin, catalase, and their combination decreased blood pressure to near control values (all P<0.05). NOX4 mRNA activity was higher in the renal tissue of CsA rats by approximately 63% (P<0.05) compared to controls but was reduced in apocynin (by 64%), catalase (by 33%) and combined treatment with apocynin and catalase (by 84%) compared to untreated CsA rats. Treatment of CsA rats with apocynin, catalase, and their combination prevented hypertension and restored renal functional parameters and tissue Nox4 expression in this model. NADPH inhibition and H2O2 scavenging is an important therapeutic strategy during CsA nephrotoxicity and hypertension.
Characterization of renal hemodynamic and structural alterations in rat models of renal impairment: role of renal sympathoexcitation

Salman IM, Ameer OZ, Sattar MA, Abdullah NA, Yam MF, Najim HS, et al.

J Nephrol, 2010 5 4;24(1):68-77.
PMID: 20437405 DOI: 10.5301/jn.2010.6

BACKGROUND: Renal sympathetic innervation plays an important role in the control of renal hemodynamics and may therefore contribute to the pathophysiology of many disease states affecting the kidney. Thus, the present study aimed to investigate the role of the renal sympathetic nervous system in the early deteriorations of renal hemodynamics and structure in rats with pathophysiological states of renal impairment.

METHODS: Anesthetized Sprague Dawley (SD) rats with cisplatin-induced acute renal failure (ARF) or streptozotocin (STZ)-induced diabetes mellitus (DM) were subjected to a renal hemodynamic study 7 days after cisplatin and STZ administration. During the acute study, renal nerves were electrically stimulated, and responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation. Post mortem kidney collection was performed for histopathological assessment.

RESULTS: In innervated ARF or DM rats, renal nerve stimulation produced significantly lower (all p<0.05, vs. innervated control) renal vasoconstrictor responses. These responses were markedly abolished when renal denervation was performed (all p<0.05); however, they appeared significantly higher compared with denervated controls (all p<0.05). Kidney injury was suppressed in denervated ARF, while, irrespective of renal denervation, renal specimens from DM rats were comparable to controls.

CONCLUSIONS: Renal sympathoexcitation is involved in the pathogenesis of the renal impairment accompanying ARF and DM, and may even precede the establishment of an observable renal injury. There is a possible enhancement in the renal sensitivity to intrarenal norepinephrine following renal denervation in ARF and DM rats.
Fulltext Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging

Mittal P, Condina MR, Klingler-Hoffmann M, Kaur G, Oehler MK, Sieber OM, et al.

Cancers (Basel), 2021 Oct 27;13(21).
PMID: 34771551 DOI: 10.3390/cancers13215388

Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.2% sensitivity and 98.6% specificity). Moreover, our machine learning approach predicted the presence of lymph node metastasis (LNM) for primary tumours of EC with an accuracy of 80% (90% sensitivity and 69% specificity). Our results demonstrate the capability of MALDI MSI for complementing classic histopathological examination for cancer diagnostic applications.
Fulltext Adipocytokine Regulation and Antiangiogenic Activity Underlie the Molecular Mechanisms of Therapeutic Effects of Phyllanthus niruri against Non-Alcoholic Fatty Liver Disease

Zarzour RHA, Alshawsh MA, Asif M, Al-Mansoub MA, Mohamed Z, Ahmad M, et al.

Nutrients, 2018 Aug 09;10(8).
PMID: 30096951 DOI: 10.3390/nu10081057

The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague⁻Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.
Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases

Li CMY, Briggs MT, Lee YR, Tin T, Young C, Pierides J, et al.

Clin Exp Med, 2024 Mar 16;24(1):53.
PMID: 38492056 DOI: 10.1007/s10238-024-01311-5

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.
Fulltext Epidemiology of smoking among Malaysian adult males: prevalence and associated factors

Lim HK, Ghazali SM, Kee CC, Lim KK, Chan YY, Teh HC, et al.

BMC Public Health, 2013 Jan 07;13:8.
PMID: 23294728 DOI: 10.1186/1471-2458-13-8

BACKGROUND: Three National Health and Morbidity Surveys (NHMSs) had been conducted in Malaysia in 10-year intervals from 1986-2006. Based on the latest NHMS survey in 2006, we describe the prevalence of smoking and identify the social and demographic factors associated with smoking among adult males in Malaysia.
METHODS: A cross-sectional study among 15,639 Malaysian adult males aged 18 years and above was conducted using proportional to size stratified sampling method. The socio-demographic variables examined were level of education, occupation, marital status, residential area, age group and monthly household income.
RESULTS: The prevalence of smoking among adult males in Malaysia was 46.5% (95% CI: 45.5-47.4%), which was 3% lower than a decade ago. Mean age of smoking initiation was 18.3 years, and mean number of cigarettes smoked daily was 11.3. Prevalence of smoking was highest among the Malays (55.9%) and those aged 21-30 years (59.3%). Smoking was significantly associated with level of education (no education OR 2.09 95% CI (1.67-2.60), primary school OR 1.95, 95% CI (1.65-2.30), secondary school OR 1.88, 95% CI (1.63-2.11), with tertiary education as the reference group). Marital status (divorce OR 1.67, 95% CI (1.22-2.28), with married as the reference group), ethnicity (Malay, OR 2.29, 95% CI ( 1.98-2.66; Chinese OR 1.23 95% CI (1.05-1.91), Other Bumis OR 1.75, 95% CI (1.46-2.10, others OR 1.48 95% CI (1.15-1.91), with Indian as the reference group), age group (18-20 years OR 2.36, 95% CI (1.90-2.94); 20-29 years OR 3.31 , 95% CI 2.82-3.89; 31-40 years OR 2.85 , 95% CI ( 2.47-3.28); 41-50 years OR 1.93, 95% CI (1.69-2.20) ; 51-60 years OR 1.32, 95% CI (1.15-1.51), with 60 year-old and above as the reference group) and residential area (rural OR 1.12 , 95% CI ( 1.03-1.22)) urban as reference.
CONCLUSION: The prevalence of smoking among Malaysian males remained high in spite of several population interventions over the past decade. Tobacco will likely remain a primary cause of premature mortality and morbidity in Malaysia. Continuous and more comprehensive anti-smoking policy measures are needed in order to further prevent the increasing prevalence of smoking among Malaysian men, particularly those who are younger, of Malay ethnicity, less educated, reside in rural residential area and with lower socio-economic status.
Fulltext Relationship between coping styles and lipid profile among public university staff

Ariaratnam S, Krishnapillai AD, Daher AM, Fadzil MA, Razali S, Omar SA, et al.

Lipids Health Dis, 2017 Feb 28;16(1):50.
PMID: 28245847 DOI: 10.1186/s12944-017-0438-1

BACKGROUND: The scarcity of data about coping styles with a biochemical marker namely lipid profile, potentially associated with cardiovascular risk factors is most striking among professionals working in public university. Hence, this research aimed to investigate the relationship between coping styles and lipid profile comprising total cholesterol (TC), triglyceride (TG), HDL-cholesterol (high density lipoprotein-cholesterol) and LDL-cholesterol (Low density lipoprotein-cholesterol) among this group of professionals.
METHODS: A cross sectional survey was conducted among staff from a tertiary education centre. Subjects were contacted to ascertain their medical history. A total of 320 subjects were interviewed and 195 subjects were eligible and subsequently recruited on a suitable date for taking blood and administration of the questionnaires. The subjects completed questionnaires pertaining to demographic details and coping styles. Pearson's correlation coefficient was used to measure the strength of association between lipid profile and coping styles.
RESULTS: Majority of the subjects were non-academic staff (60.0%), female (67.2%), Malay (91.8%), married (52.3%) and educated until Diploma level (34.9%). Academic staff scored significantly higher mean scores in task-oriented coping styles (Mean = 64.12). Non-academic staff scored significantly higher mean scores in emotion (Mean = 48.05) and avoidance-oriented coping styles (Mean = 57.61). Malay subjects had significantly higher mean scores in emotion (Mean = 47.14) and avoidance-oriented coping styles (Mean = 55.23). Non-malay subjects (Mean = 66.00) attained significantly higher mean scores in task-oriented coping styles. Single/divorced/widowed individuals scored significantly higher mean scores in emotion (Mean = 48.13) and avoidance-oriented coping styles (Mean = 56.86). There was a significant negative correlation between TC (r = -0.162) and LDL (r = -0.168) with avoidance-oriented coping styles (p = 0.023, p = 0.019 respectively).
CONCLUSION: Avoidance-oriented coping style was more likely to engender favourable lipid profile. Hence, assessment of coping styles would certainly assist health care practitioners in predicting subjects who would be at a greater risk of developing cardiovascular diseases.
Evaluation of toxicity profile of kratom (Mitragyna speciosa Korth) decoction in rats

Hassan Z, Singh D, Suhaimi FW, Chear NJ, Harun N, See CP, et al.

Regul Toxicol Pharmacol, 2023 Sep;143:105466.
PMID: 37536550 DOI: 10.1016/j.yrtph.2023.105466

Mitragyna speciosa Korth also known as kratom, is an herbal drug preparation for its therapeutic properties and opioid-replacement therapy. Kratom is consumed in a brewed decoction form in Malaysia and to date, no studies have characterized its chemical and toxicity profile. Thus, this study aims to evaluate kratom decoction's safety and toxicity profile after 28 days of treatment. Mitragynine content was quantified in kratom decoction and used as a marker to determine the concentration. Male and female Sprague Dawley rats were orally treated with vehicle or kratom decoction (10, 50 or 150 mg/kg) and two satellite groups were treated with vehicle and kratom decoction (150 mg/kg). Blood and organs were collected for hematology, biochemical and histopathology analysis at the end of treatment. No mortality was found after 28 days of treatment and no significant changes in body weight and hematology profile, except for low platelet count. High amounts of uric acid, AST, ALT and alkaline phosphatase were found in the biochemical analysis. Histological investigation of the heart and lungs detected no alterations except for the kidney, liver and brain tissues. In conclusion, repeated administration of kratom decoction provided some evidence of toxicity in the kidney and liver with no occurrence of mortality.
Fulltext What information and the extent of information research participants need in informed consent forms: a multi-country survey

Karbwang J, Koonrungsesomboon N, Torres CE, Jimenez EB, Kaur G, Mathur R, et al.

BMC Med Ethics, 2018 09 15;19(1):79.
PMID: 30219106 DOI: 10.1186/s12910-018-0318-x

BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research.
METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important).
RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively).
CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.