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  1. Jha C, Ullas Kamath S, Dash S, Prabhu Attur R, Ramachandra L, Shenoy Kallya R
    Rep Biochem Mol Biol, 2019 Apr;8(1):72-78.
    PMID: 31334291
    Background: Following contrast-enhanced computed tomography (CECT) contrast-induced nephropathy (CIN) may occur in patients with renal insufficiency or diabetes. Creatinine, the most common marker of CIN, may not be an accurate measure of damage and is affected by many non-renal factors. Our aim was to evaluate ischemia-modified albumin (IMA) as an early CIN marker and correlate it with paraoxonase-1 (PON-1) and creatinine before and after CECT.

    Methods: Forty-eight adult patients scheduled for intravenous CECT, regardless of indication or body region for CECT, were included in this prospective study. Venous blood samples were obtained 12-24 hours before and after contrast media (CM) administration. Ischemia-modified albumin and PON-1 were estimated using methods described by Bar-Or et al. and Dantoine et.al., respectively. Creatinine was estimated on an automated analyzer.

    Results: Significant differences in IMA (P < 0.001) and PON-1 (P < 0.001) levels were found between pre- and post-CECT samples, while the difference for creatinine was not significant (p = 0.073). No correlation was found between IMA and PON-1 or IMA and creatinine in either the pre- or post-CECT samples.

    Conclusion: After CM administration patients are subjected to oxidative stress and/or ischemia, as revealed by elevated IMA and decreased PON-1 levels; however, creatinine levels, most commonly estimated to assess reduced renal function, did not reflect the condition accurately. IMA may be a sensitive marker for CIN but further studies are required to confirm its usefulness.

  2. Sushith S, Krishnamurthy HN, Reshma S, Janice D, Madan G, Ashok KJ, et al.
    Rep Biochem Mol Biol, 2020 Jul;9(2):241-249.
    PMID: 33178875 DOI: 10.29252/rbmb.9.2.241
    Background: The objective of this study was to determine the levels of serum ischemia-modified albumin (IMA), fibrinogen (FIB) and high sensitivity C-reactive protein (hs-CRP) in type 2 diabetes mellitus (T2DM) patients with hypertension (HT) (DMT2HTN) and without HT (DMT2). Also, their association with certain biochemical and physical factors were studied to identify possible risk factors that lead to cardiovascular complications.

    Methods: Fasting blood samples were collected from 35 DMT2 or DMT2HTN patients each to analyze differences in serum and plasma levels of IMA, hs-CRP, FIB, total cholesterol (TC), high and low density lipoproteins (HDL and LDL), triglyceride (TG), hemoglobin A1c (HbA1C), glycated hemoglobin and creatinine.

    Results: In DMT2 and DMT2HTN patients, IMA, hs-CRP, FIB, TC, TG, HDL, LDL, glycated hemoglobin and creatinine levels, including body mass index (BMI) and waist-to-hip ratio (WHR), were significantly higher relative to healthy controls. In addition, the levels of IMA, hs-CRP and FIB levels showed a strong link to BMI, WHR, TC, TG, LDL and glycated hemoglobin. Lastly, both DMT2 and DMT2HTN patients demonstrated a significant reduction in HDL.

    Conclusion: DMT2 and DMT2HTN patients have a greater risk of developing cardiovascular related complications. This study suggests that quantifying hs-CRP, IMA and FIB levels can help diagnose the risk of developing complications during the early stages of metabolic and cardiovascular disease. Overall, the specific risk factors may be used for early identification of cardiovascular complications to decrease mortality and morbidity in T2DM patients.

  3. Chan HH, Leong YQ, Voon SM, Pan ML, Leong CO, Lim CL, et al.
    Rep Biochem Mol Biol, 2021 Jan;9(4):417-425.
    PMID: 33969135 DOI: 10.52547/rbmb.9.4.417
    Background: Alzheimer's disease (AD) is a neurodegenerative disorder that causes cognitive dysfunction. Previous studies have suggested that amyloid plaques, mainly comprising of amyloid-beta peptides, play a pivotal role in AD pathophysiology. This study focuses on the evaluation of the effects of amyloid precursor protein (APP) overexpression on NF-κB, Rho-GTPase and Bcl-2 mediated pro-apoptotic pathways in neuronal cells.

    Methods: A lentiviral transduction system was used to generate SH-SY5Y cells overexpressing APP. Immunoblotting was conducted to determine expression levels of NF-κB, Rho-GTPase, and Bcl-2 family proteins in the APP overexpressed cells.

    Results: In the NF-κB signaling pathway, APP-overexpressing SH-SY5Y cells showed that there was a reduction of p-NF-κB (p< 0.05) and IKKα. Subsequently, there was upregulation of protein expression of NF-Κb, IKKβ and IκBα. On the other hand, protein expression of RhoC (p< 0.05) and Rac1/2/3 was upregulated as compared to the control group. Meanwhile, a decrease in RhoA, Cdc42 (p< 0.05) and p-Rac1/cdc42 protein levels was observed in the APP-overexpressed group. Lastly, in the pro-apoptotic pathway, the expression of Bcl-2, Bid, Bok and Puma (p< 0.05) was up regulated in the APP-overexpressed group. Downregulation of Bad and Bim expression was observed in the APP-overexpressed as compared to the control group, and Bax expression remained unchanged in the APP-overexpressed group.

    Conclusion: APP overexpression regulated signaling in the NF-κB, Rho-GTPase and Bcl-2 family pathways in neuronal cells, suggesting that these are involved in promoting neuronal survival and modulating synaptic plasticity in AD. However, further studies are essential to elucidate the APP-mediated mechanism of action.

  4. Ilias AN, Ismail IS, Hamzah H, Mohd Mohidin TB, Idris MF, Ajat M
    Rep Biochem Mol Biol, 2021 Oct;10(3):477-487.
    PMID: 34981026 DOI: 10.52547/rbmb.10.3.477
    BACKGROUND: Rebaudioside A is one of the major diterpene glycosides found in Stevia had been reported to possess anti-hyperlipidemic effects. In this study, we explore the potential cholesterol-regulating mechanisms of Rebaudioside A in the human hepatoma (HepG2) cell line in comparison with simvastatin.

    METHODS: Cells were incubated with Rebaudioside A at several concentrations (0-10 µM) to determine the cytotoxicity by the MTT assay. Cells were treated with selected dosage (1 and 5 µM) in further experiments. Total cellular lipid was extracted by Bligh and Dyer method and subjected to quantitative colorimetric assay. To illustrate the effect of Rebaudioside A on cellular lipid droplets and low-density lipoprotein receptors, treated cells were subjected to immunofluorescence microscopy. Finally, we investigated the expression of experimental gene patterns of cells in response to treatment.

    RESULTS: In this study, cytotoxicity of Rebaudioside A was determined at 27.72 µM. Treatment of cells with a higher concentration of Rebaudioside A promotes better hepatocellular cholesterol internalization and ameliorates cholesterol-regulating genes such as HMGCR, LDLR, and ACAT2.

    CONCLUSION: In conclusion, our data demonstrated that Rebaudioside A is capable to regulate cholesterol levels in HepG2 cells. Hence, we proposed that Rebaudioside A offers a potential alternative to statins for atherosclerosis therapy.

  5. Govindasamy N, Chung Chok K, Ying Ng P, Yian Koh R, Moi Chye S
    Rep Biochem Mol Biol, 2022 Apr;11(1):63-73.
    PMID: 35765532 DOI: 10.52547/rbmb.11.1.63
    BACKGROUND: Peripheral nerve injury (PNI) is a common condition that compromises motor and sensory functions. Peripheral nerves are known to have regenerative capability and the pineal hormone, melatonin, is known to aid nerve regeneration. However, the role of Schwann cells and the pathways involved remain unclear. Thus, the aim of this study is to identify the effects of melatonin on Schwann cell proliferation, dedifferentiation, and the involvement of nuclear factor kappa light chain enhancer of activated B cells (NF-ĸB), focal adhesion kinase (FAK) and proto-oncogene tyrosine-protein kinase, Src pathways in this process.

    METHODS: Schwann cells was treated with melatonin and its proliferation and dedifferentiation were identified using MTT assay and immunofluorescence staining for SRY (sex determining region Y)-box 2 (SOX2). Next, the protein expressions of NF-ĸB, FAK and Src pathways were identified by Western blot.

    RESULTS: MTT results confirmed increased proliferation of Schwann cells with melatonin treatment, and it was highest at 10 μM melatonin. Immunofluorescent staining revealed an increase in the green fluorescence staining for SOX2 in melatonin-treated cells, showing enhanced dedifferentiation. Western blot assay revealed melatonin increased phospho-NF-ĸB (PNF-ĸB), IKK-α, FAK (D2R2E), phospho-FAK (Tyr 576/577 and Tyr 397) protein expressions as compared with control. However, Src (32G6), Lyn (C13F9), Fyn, Csk (C74C1) protein expressions were not increased as compared with control.

    CONCLUSION: Melatonin promotes Schwann cell proliferation and dedifferentiation via NF-ĸB, FAK-dependent but Src-independent pathways.

  6. Cheah CH, Ling APK, Wong YP, Koh RY, Hussein S
    Rep Biochem Mol Biol, 2022 Apr;11(1):125-137.
    PMID: 35765526 DOI: 10.52547/rbmb.11.1.125
    BACKGROUND: It is believed that activation of microglia in the central nervous system upon detection of stimulus like lipopolysaccharides provokes neuroinflammation via the production of pro-inflammatory mediators and cytokines. The cytoprotective and anti-inflammatory properties of various folk medicine has been gaining attention as a strategy to combat various disease. This study aimed to assess the anti-neuroinflammatory properties of chloroform extract of in vitro Panax ginseng root culture based on nitric oxide and cytokines production.

    METHODS: The study was initiated with the determination of maximum non-toxic dose (MNTD) of P. ginseng root culture chloroform extract using the MTT assay. The lipopolysaccharides-stimulated BV2 microglia cells were treated with MNTD and ½MNTD of the extract and its anti-neuroinflammatory properties were assessed by measuring the production of nitric oxide (NO) via Griess assay, as well as TNF-α, IL-6 and IL-10 using Quantikine ELISA.

    RESULTS: It was found that the MNTD and ½MNTD of the extract did not play a significant role in the production of pro-inflammatory cytokines such as NO, TNF-α and IL-6. However, the MNTD and ½MNTD of chloroform extract significantly increased the anti-inflammatory IL-10 compared to the untreated cells.

    CONCLUSION: With this, the chloroform extract of P. ginseng root culture potentially exerts anti-neuroinflammatory properties.

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