Displaying publications 461 - 480 of 1115 in total

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  1. Pian AK, Foong CP, Hamid RA
    Life Sci, 2022 Dec 15;311(Pt B):121161.
    PMID: 36375571 DOI: 10.1016/j.lfs.2022.121161
    We have previously reported the inhibition of thioredoxin reductase (TrxR) and invasion by tricyclohexylphosphine gold (I) n-mercaptobenzoate (n = 2, 3, 4) labeled as 1-3 towards MCF-7 cells, in vitro. Nevertheless, the mode of death and its apoptotic pathway has yet to be revealed. The main aim of this study is to investigate the anti-neoplastic activity of this phosphanegold (I) thiolates against breast adenocarcinoma cells, MCF-7. Herein, we explored the role of gold(I) series, 1-3 for their apoptosis-inducing ability against MCF-7 cells. They were scrutinized for their antiproliferative activities which exhibited their IC50 values of 8.14 μM ± 0.10, 7.26 μM ± 0.33, and 9.03 μM ± 0.69, respectively, and indicated better cytotoxicities than that of cisplatin (positive control). Further, the mechanisms of their actions were studied by analyzing the status of ROS generation (by DCFH-DA), cytochrome c release (by ELISA), and activation of caspases 3/7, 8, 9, and 10, annexin V staining and cell cycle analysis by flow cytometry, respectively. It was observed that the compounds, 1-3 can promote ROS generation, cytochrome c release, and activation of caspases 3/7, caspase 8, caspase 9, and caspase 10 on MCF-7 cells. In addition, the compounds are shown to induce MCF-7 cell arrest at S-phase. Gene analysis via PCR array further clarified their effects by modulating the related genes upon the compounds' treatment. Further investigation on other breast cancer cells as well as in vivo studies on these compounds will further increase their potential as anti-breast cancer agents.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  2. Mohd Sabri NA, Lee SK, Murugan DD, Ling WC
    Sci Rep, 2022 Oct 21;12(1):17633.
    PMID: 36271015 DOI: 10.1038/s41598-022-21107-5
    Epigallocatechin gallate (EGCG) has been shown to have antihypertensive activity. However, the role of epigallocatechin gallate (EGCG) in improving vascular function via modulation of endothelial nitric oxide synthase (eNOS) in hypertensive subjects is not well researched. Angiotensin II-infused hypertensive mice (8-10 weeks old) received EGCG (50 mg/kg/day) for 14 days via oral gavage. The arterial systolic blood pressure (SBP) was measured using the tail-cuff method every three days. At the end of the treatment, the vascular reactivity of the isolated aortae was studied using wire myographs. The level of nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and tetrahydrobiopterine (BH4) were determined using assay kits while the presence of proteins (NOS, p-eNOS and NOx-2) were determined using by Western blotting. In vivo treatment with EGCG for 14 days significantly attenuated the increase in SBP, alleviated the vascular dysfunction, increased the vascular cGMP and BH4 level as well as the expression of p-eNOS and decreased elevated ROS level and NOx-2 protein in angiotensin II-infused hypertensive mice. Collectively, treatment with EGCG in hypertensive mice exerts a blood pressure lowering effect which is partly attributed to the improvement in the vascular function due to its ability to reduce vascular oxidative stress in the aortic tissue leading to a decrease in eNOS uncoupling thus increasing NO bioavailability.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  3. Zhao L, Yang L, Ahmad K
    Hum Exp Toxicol, 2023;42:9603271221146780.
    PMID: 36607234 DOI: 10.1177/09603271221146780
    OBJECTIVES: Kaempferol (KMF), has beneficial effects against hepatic lipid accumulation. In this study, we aimed to investigate molecular mechanism underlying the protective effect of KMF on lipid accumulation.

    METHODS: HepG2 cells were treated with different concentrations of KMF and 0.5 mM palmitate (PA) for 24  h. The mRNA and protein levels of genes involved in lipid metabolism were evaluated using real-time PCR and western blot. The expression of Nrf2 was silenced using siRNA.

    RESULTS: Data indicated that KMF (20 μM) reversed PA-induced increased triglyceride (TG) levels and total lipid content. These effects were accompanied by down-regulation of the mRNA and protein levels of lipogenic genes (FAS, ACC and SREBP1), and up-regulation of genes related to fatty acid oxidation (CPT-1, HADHα and PPARα). Kaempferol significantly decreased the levels of the oxidative stress markers (ROS and MDA) and enhanced the activities of antioxidant enzymes SOD and GPx in PA-challenged cells. Luciferase analysis showed that KMF increased the transactivation of Nrf2 in hepatocytes. The results also revealed that KMF-mediated activation of Nrf2 target genes was suppressed by Nrf2 siRNA. Furthermore, Nrf2 siRNA abolished the KMF-induced reduction in ROS and MDA levels in PA treated cells. In addition, the inhibitory effect of KMF on TG levels and the mRNA and protein levels of FAS, ACC and SREPB-1 were significantly abolished by Nrf2 inhibition. Nrf2 inhibition also suppressed the KMF-induced activation of genes involved in β oxidation (CPT-1 and PPAR-α).

    CONCLUSION: The results suggest that KMF protects HepG2 cells from PA-induced lipid accumulation via activation of the Nrf2 signaling pathway.

    Matched MeSH terms: Reactive Oxygen Species/metabolism
  4. Sugito SFA, Wibrianto A, Chang JY, Fahmi MZ, Khairunisa SQ, Sakti SCW, et al.
    Dalton Trans, 2024 Jul 09;53(27):11368-11379.
    PMID: 38896134 DOI: 10.1039/d4dt01123f
    The design of multimodal cancer therapy was focused on reaching an efficient process and minimizing harmful effects on patients. In the present study, the Au-MnO2 nanostructures have been successfully constructed and produced as novel multipurpose photosensitive agents simultaneously for photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT). The prepared AuNPs were conjugated with MnO2 NPs by its participation in the thermal decomposition process of KMnO4 confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy (FT-IR). The 16.5 nm Au-MnO2 nanostructure exhibited an absorbance at 438 nm, which is beneficial for application in light induction therapy due to the NIR band, as well as its properties of generating reactive oxygen species (ROS) associated with the 808 nm laser light for PDT. The photothermal transduction efficiency was calculated and compared with that of the non-irradiated nanostructure, in which it was found that the 808 nm laser induced a high efficiency of 83%, 41.5%, and 37.5% for PDT, PTT, and CDT, respectively. The results of DPBF and TMB assays showed that the efficiency of PDT and PTT was higher than that of CDT. The nanostructure also confirmed the time-dependent peroxidase properties at different H2O2, TMB, and H2TMB concentrations, promising good potency in applying nanomedicine in clinical cancer therapy.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  5. Thegarathah P, Jewaratnam J, Simarani K, Elgharbawy AAM
    PeerJ, 2024;12:e17151.
    PMID: 39026538 DOI: 10.7717/peerj.17151
    BACKGROUND: The booming palm oil industry is in line with the growing population worldwide and surge in demand. This leads to a massive generation of palm oil mill effluent (POME). POME is composed of sterilizer condensate (SC), separator sludge (SS), and hydro-cyclone wastewater (HCW). Comparatively, SS exhibits the highest organic content, resulting in various environmental impacts. However, past studies mainly focused on treating the final effluent. Therefore, this pioneering research investigated the optimization of pollutant removal in SS via different aspects of bioremediation, including experimental conditions, treatment efficiencies, mechanisms, and degradation pathways.

    METHODS: A two-level factorial design was employed to optimize the removal of chemical oxygen demand (COD) and turbidity using Aspergillus niger. Bioremediation of SS was performed through submerged fermentation (SmF) under several independent variables, including temperature (20-40 °C), agitation speed (100-200 RPM), fermentation duration (72-240 h), and initial sample concentration (20-100%). The characteristics of the treated SS were then compared to that of raw sludge.

    RESULTS: Optimal COD and turbidity removal were achieved at 37 °C 100 RPM, 156 h, and 100% sludge. The analysis of variance (ANOVA) revealed a significant effect of selective individual and interacting variables (p oxygen demand (BOD), oil and grease (OG), color, and carbon content. In short, this study demonstrated the effectiveness of A. niger in treating SS through the application of a two-level factorial design.

    Matched MeSH terms: Biological Oxygen Demand Analysis*
  6. Farghadani R, Lim HY, Abdulla MA, Rajarajeswaran J
    Bioorg Chem, 2024 Nov;152:107730.
    PMID: 39216194 DOI: 10.1016/j.bioorg.2024.107730
    Breast cancer is the most prevalent cancer among women globally, with triple-negative breast cancer (TNBC) associated with poor prognosis and low five-year survival rates. Schiff base compounds, known for their extensive pharmacological activities, have garnered significant attention in cancer drug research. This study aimed to evaluate the anticancer potential of a novel β-diiminato compound and elucidate its mechanism of action. The compound's effect on cell viability was assessed using MTT assays in breast cancer cell lines including MCF-7 and MDA-MB-231. Cytotoxic effects were further analyzed using trypan blue exclusion and lactate dehydrogenase (LDH) release assays. In order to assess the mechanism of inhibitory activity and mode of cell death induced by this compound, flow cytometry of cell cycle distribution and apoptosis analysis were carried out. Apoptosis incidence was initially assessed through cell and nuclear morphological changes (Hoechst 33342/Propidium iodide (PI) staining) and further confirmed by Annexin V/PI staining and flow cytometry analysis. In addition, the effect of this compound on the disruption of mitochondrial membrane potential (MMP) and generation of the reactive oxygen species (ROS) was determined using the JC-1 indicator and DCFDA dye, respectively. The results demonstrated that the 24 h treatment with β-diiminato compound significantly suppressed the viability of MDA-MB-231 and MCF-7 cancer cells in a dose-dependent manner with the IC50 value of 2.41 ± 0.29 and 3.51 ± 0.14, respectively. The cytotoxic effect of the compound was further confirmed with a dose-dependent increase in the number of dead cells and enhanced LDH level in the culture medium. This compound exerted its anti-proliferative effect by G2/M phase cell growth arrest in MDA-MB-231 breast cancer cells and induced apoptosis-mediated cell death, which involved characteristic changes in cell and nuclear morphology, phosphatidylserine externalization, mitochondrial membrane depolarization, and increased ROS level. Neither hepatotoxicity nor nephrotoxicity was detected in the biochemical and histopathological analysis confirming the safety characterization of this compound usage. Therefore, the results significantly confirmed the potential anticancer activity of a novel β-diiminato compound, as evidenced by the induction of cell cycle arrest and apoptosis, which might be driven by the ROS‑mediated mitochondrial death pathway. This compound can be a promising candidate for future anticancer drug design and TNBC treatment, and further preclinical and clinical studies are warranted.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  7. Wong YE, Razif MFM, Ng ST, Tan CS, Fung SY, Murugan DD
    Int J Med Mushrooms, 2024;26(11):27-40.
    PMID: 39241161 DOI: 10.1615/IntJMedMushrooms.2024055061
    Hypertension is a risk factor for cardiovascular diseases such as coronary artery disease, heart failure, and stroke. Lignosus rhinocerus (Cooke) Ryvarden (also known as tiger milk mushroom), has been reported to exhibit a range of pharmacological effects, such as anti-inflammatory, anti-proliferative, antioxidative, immunomodulatory and anti-asthmatic activities. Thus far, there is limited research that has explored its ability to mediate vascular effects in vivo. Therefore, this study investigated the antihypertensive and vascular protective effects of L. rhinocerus TM02® sclerotia supplementation in spontaneously hypertensive rats (SHR). Wistar Kyoto (WKY) rats served as a normotensive control group. SHR were orally administered with L. rhinocerus TM02® sclerotia (100 mg/kg and 300 mg/kg, respectively) for 8 weeks, and blood pressure was monitored every 2 weeks. Vascular function was evaluated using an organ bath (aorta) and wire myograph (renal artery) at the treatment endpoint. The levels of reactive oxygen species (ROS) and nitric oxide (NO) in the aorta and renal artery were evaluated using dihydroethidium (DHE) and difluoro fluorescein acetate (DAF-FM) fluorescence assays, respectively. Total plasma nitrate/nitrite and tumor necrosis factor alpha (TNF-α) levels were evaluated via colorimetric assays. In vivo treatment with L. rhinocerus TM02® sclerotia significantly attenuated the increase in systolic blood pressure (SBP). It also alleviated vascular dysfunction and decreased elevated ROS in the aorta and renal arteries of the treated SHRs. Moreover, L. rhinocerus TM02® sclerotia attenuated plasma TNF-α level but increased total plasma nitrate/nitrite, albeit slightly, coupled with significantly increased NO at the vascular level. Collectively, the present study demonstrated that L. rhinocerus TM02® sclerotia supplementation exerted blood pressure lowering effects, partly attributed to improvements in vascular function via reduction in vascular oxidative stress.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  8. Retinasamy T, Lee ALY, Lee HS, Lee VLL, Shaikh MF, Yeong KY
    ACS Chem Neurosci, 2024 Sep 18;15(18):3298-3310.
    PMID: 39213521 DOI: 10.1021/acschemneuro.4c00205
    Alzheimer's disease is a significant global health issue, and studies suggest that neuroinflammation plays a vital role in the advancement of this disease. In this study, anakinra has been shown to display a time- and concentration-dependent antineuroinflammatory effect. In the in vitro studies, it diminished the gene expressions of tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO) synthase 2 stimulated by lipopolysaccharide (LPS). Anakinra also reduced the LPS-induced production of NO and reactive oxygen species. Thus, the hypertrophic state of LPS-activated BV2 microglial cells was reversed by anakinra. Furthermore, acrylamide (ACR)-induced activation of nuclear transcription factor-κB, TNF-α, and interleukin-1β was downregulated, while cAMP response element binding protein and brain-derived neurotrophic factor expression levels were markedly enhanced in ACR-treated zebrafish larvae. It was also observed that anakinra improved the uncoordinated swimming behaviors in ACR-exposed zebrafish larvae. Overall, anakinra demonstrated potential antineuroinflammatory and antioxidative effects.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  9. Ho JJ, Kidman AM, Chua B, Chang G, Fiander M, Davis PG
    Cochrane Database Syst Rev, 2024 Oct 11;10(10):CD000143.
    PMID: 39392114 DOI: 10.1002/14651858.CD000143.pub2
    BACKGROUND: Preterm infants who are extubated following a period of invasive ventilation via an endotracheal tube are at risk of developing respiratory failure, leading to reintubation. This may be due to apnoea, respiratory acidosis, or hypoxia. Historically, preterm infants were extubated to head box oxygen or low-flow nasal cannulae. Support with non-invasive pressure might help improve rates of successful extubation in preterm infants by stabilising the upper airway, improving lung function, and reducing apnoea. This is an update of a review first published in 1997 and last updated in 2003.

    OBJECTIVES: To determine whether nasal continuous positive airway pressure (NCPAP), applied immediately after extubation of preterm infants, reduces the incidence of extubation failure and the need for additional ventilatory support, without clinically important adverse events.

    SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries on 22 September 2023 using a revised strategy. We searched conference abstracts and the reference lists of included studies and relevant systematic reviews.

    SELECTION CRITERIA: Eligible trials employed random or quasi-random allocation of preterm infants undergoing extubation. Eligible comparisons were NCPAP (delivered by any device and interface) versus head box oxygen, extubation to room air, or any other form of low-pressure supplemental oxygen. We grouped the comparators under the term no continuous positive airway pressure (no CPAP).

    DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data from the included studies. Where studies were sufficiently similar, we performed a meta-analysis, calculating risk ratios (RRs) with their 95% confidence intervals (CIs) for dichotomous data. For the primary outcomes that showed an effect, we calculated the number needed to treat for an additional beneficial outcome (NNTB). We used the GRADE approach to assess the certainty of the evidence for clinically important outcomes.

    MAIN RESULTS: We included nine trials (with 726 infants) in the quantitative synthesis of this updated review. Eight studies were conducted in high-income countries between 1982 and 2005. One study was conducted in Chile, which was classified as upper-middle income at the time of the study. All studies used head box oxygen in the control arm. Risk of bias was generally low. However, due to the inherent nature of the intervention, no studies incorporated blinding. Consequently, the neonatal intensive care unit staff were aware of the assigned group for each infant, and we judged all studies at high risk of performance bias. However, we assessed blinding of the outcome assessor (detection bias) as low risk for seven studies because they used objective criteria to define both primary outcomes. NCPAP compared with no CPAP may reduce the risk of extubation failure (RR 0.62, 95% CI 0.51 to 0.76; risk difference (RD) -0.17, 95% -0.23 to -0.10; NNTB 6, 95% CI 4 to 10; I2 = 55%; 9 studies, 726 infants; low-certainty evidence) and endotracheal reintubation (RR 0.79, 95% 0.64 to 0.98; RD -0.07, 95% CI -0.14 to -0.01; NNTB 15, 95% CI 8 to 100; I2 = 65%; 9 studies; 726 infants; very low-certainty evidence), though the evidence for endotracheal reintubation is very uncertain. NCPAP compared with no CPAP may have little or no effect on bronchopulmonary dysplasia, but the evidence is very uncertain (RR 0.89, 95% CI 0.47 to 1.68; RD -0.03, 95% CI -0.22 to 0.15; 1 study, 92 infants; very low-certainty evidence). No study reported neurodevelopmental outcomes.

    AUTHORS' CONCLUSIONS: NCPAP may be more effective than no CPAP in preventing extubation failure in preterm infants if applied immediately after extubation from invasive mechanical ventilation. We are uncertain whether it can reduce the risk of reintubation or bronchopulmonary dysplasia. We have no information on long-term neurodevelopmental outcomes. Although there is only low-certainty evidence for the effectiveness of NCPAP immediately after extubation in preterm infants, we consider there is no need for further research on this intervention, which has become standard practice.

    Matched MeSH terms: Oxygen Inhalation Therapy/methods
  10. Nagaraj B, Sivasubramanian A, Musthafa SA, Muhammad S, Anilkumar AK, Munuswamy-Ramanujam G, et al.
    Free Radic Biol Med, 2024 Nov 20;225:925-932.
    PMID: 39393554 DOI: 10.1016/j.freeradbiomed.2024.10.275
    3-deoxycaryoptinol (Clerodin) is a clerodane diterpene isolated from the leaves of Clerodendrum infortunatum. The present research investigates the anticancer therapeutic efficacy of clerodin in human monocytic leukemic (THP-1) cells for the first time. In vitro assay using THP-1 cells showed the cytotoxic ability of clerodin. Further, Annexin-V(FITC)/PI and intracellular ROS (DCFDA) assays carried out using flow cytometry, and confocal laser scanning microscopy confirmed the apoptotic potential of clerodin. Moreover, the Western blot was used to detect mitochondrial apoptosis of THP-1 cells. RT-PCR, ELISA, and Western blot analysis clearly indicated that clerodin significantly increased the expression of pro-apoptotic marker caspase-3 in THP-1 cells. clerodin also selectively targeted the G2/M phase of THP-1 cells, a key feature for anticancer molecules. Importantly, the clerodin did not exhibit cytotoxicity against human peripheral blood cells. These properties of clerodin make it a potential chemotherapeutic agent that can selectively induce apoptosis in leukemia-like cancer cells.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  11. Zhang S, Song H, Chang M, Lu Y, Liu S, Wu J, et al.
    Int J Biol Macromol, 2025 Apr;304(Pt 2):140973.
    PMID: 39952536 DOI: 10.1016/j.ijbiomac.2025.140973
    Cisplatin (Cis) is among the most widely employed antitumour agents, although its clinical application is limited by self-induced multiple-organ toxicity. Previous studies have demonstrated the essential role of mitochondrial injury in the pathogenesis of Cis-induced ovotoxicity. Notably, mesenchymal stem cell-extracellular vesicles (MSC-EVs), potential cell-free therapeutic agents, exhibit pronounced advantages for the treatment of ovarian dysfunction. However, little is known about which core component contained in MSC-EVs plays a major role in repairing Cis-induced ovarian damage, and further, the potential mechanisms underlying the repair of mitochondrial damage remain unclear. Herein, our study first verified that MSC-EVs effectively ameliorate Cis-induced ovarian dysfunction by upregulating the level of mitochondrion-localized glutamic acid-rich protein (MGARP), after which MGARP repairs mitochondrial damage and inhibits cellular ROS production by combining with and suppressing the degradation of peroxiredoxin 2 (PRDX2) in granulosa cells (GCs). More importantly, our study further showed that heat shock protein family A member 8 (HSPA8) is indispensable for MenSC-EV-mediated improvement of Cis-induced ovotoxicity. This investigation provides novel insights into the molecular mechanisms by which MSCs alleviate Cis-induced ovotoxicity through improving mitochondrial dysfunction.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  12. Chang MM, Chu DT, Lin SC, Lee JS, Vu TD, Vu HT, et al.
    Stem Cell Res Ther, 2025 Mar 11;16(1):129.
    PMID: 40069892 DOI: 10.1186/s13287-025-04164-1
    BACKGROUND: Microenvironmental alterations induce significant genetic and epigenetic changes in stem cells. Mitochondria, essential for regenerative capabilities, provide the necessary energy for stem cell function. However, the specific roles of histone modifications and mitochondrial dynamics in human adipose-derived stem cells (ASCs) during morphological transformations remain poorly understood. In this study, we aim to elucidate the mechanisms by which ASC sphere formation enhances mitochondrial function, delivery, and rescue efficiency.

    METHODS: ASCs were cultured on chitosan nano-deposited surfaces to form 3D spheres. Mitochondrial activity and ATP production were assessed using MitoTracker staining, Seahorse XF analysis, and ATP luminescence assays. Single-cell RNA sequencing, followed by Ingenuity Pathway Analysis (IPA), was conducted to uncover key regulatory pathways, which were validated through molecular techniques. Pathway involvement was confirmed using epigenetic inhibitors or PPARγ-modulating drugs. Mitochondrial structural integrity and delivery efficiency were evaluated after isolation.

    RESULTS: Chitosan-induced ASC spheres exhibited unique compact mitochondrial morphology, characterized by condensed cristae, enhanced mitochondrial activity, and increased ATP production through oxidative phosphorylation. High expressions of mitochondrial complex I genes and elevated levels of mitochondrial complex proteins were observed without an increase in reactive oxygen species (ROS). Epigenetic modification of H3K27me3 and PPARγ involvement were discovered and confirmed by inhibiting H3K27me3 with the specific EZH2 inhibitor GSK126 and by adding the PPARγ agonist Rosiglitazone (RSG). Isolated mitochondria from ASC spheres showed improved structural stability and delivery efficiency, suppressed the of inflammatory cytokines in LPS- and TNFα-induced inflamed cells, and rescued cells from damage, thereby enhancing function and promoting recovery.

    CONCLUSION: Enhancing mitochondrial ATP production via the EZH2-H3K27me3-PPARγ pathway offers an alternative strategy to conventional cell-based therapies. High-functional mitochondria and delivery efficiency show significant potential for regenerative medicine applications.

    Matched MeSH terms: Reactive Oxygen Species/metabolism
  13. Balavaishnavi B, Kamaraj M, Nithya TG, Santhosh P, GokilaLakshmi S, Shaik MR
    Med Oncol, 2024 Mar 29;41(5):103.
    PMID: 38553593 DOI: 10.1007/s12032-024-02341-5
    Rauvolfia tetraphylla is an essential medicinal plant that has been widely used in traditional medicine for various disease treatments. However, the tumor suppressor activity of R. tetraphylla and its phytocompounds were not explored against triple-negative breast cancer. The current research investigated the impact of R. tetraphylla methanolic extract (RTE) and its isolated compounds Ajmaline (RTC1) and Reserpine (RTC2) on triple-negative breast cancer cell line (MDA-MB-231) focusing on anti-proliferative effects. Our study imparts that RTE and RTC2 showed promising cytotoxic effects compared to RTC1. So further experiments have proceeded with RTE and RTC2, to evaluate its proliferation, migration, and apoptotic effect. The result shows around 80% of cells were observed in the G0/G1 phase in cell cycle analysis indicating the cell cycle inhibition and duel staining clearly showed the apoptotic effect. The migration of cells after the scratch was 60.45% observed in control and 90% in treated cells showing the inhibition of migration. ROS distribution was intense compared to control indicating the increased ROS stress in treated cells. Both RTE and RTC2-treated cells showed the potential to suppress proliferation and induce apoptotic change by upregulating BAX and MST-1 and suppressing Bcl2, LATS-1, and YAP, proving that deregulation of YAP resulting in the blockage of TEAD-YAP complex and inhibit proliferation. Therefore, R. tetraphylla extract and its isolated compounds were demonstrated to find its ability to act against MDA-MB-231 and these findings will help adjudicate it as a therapeutic drug against experimental triple-negative breast cancer.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  14. Azlan A, Khor KZ, Rajasegaran Y, Rosli AA, Said MSM, Yusoff NM, et al.
    Med Oncol, 2023 Jun 21;40(7):208.
    PMID: 37341821 DOI: 10.1007/s12032-023-02075-w
    Reactive oxygen species (ROS) homeostasis is crucial for leukaemogenesisand deregulation would hamper leukaemic progression. Although the regulatory effects of RUNX1/ETO has been extensively studied, its underlying molecular mechanims in ROS production in t(8,21) AML is yet to be fully elucidated. Here, we report that RUNX1/ETO could directly control FLT3 by occupying several DNA elements on FLT3 locus. The possible hijacking mechanism by RUNX1/ETO over FLT3 mediated ROS modulation in AML t(8;21) was made apparent when suppression of RUNX1/ETO led to decrement in ROS levels and the direct oxidative marker FOXO3 but not in FLT3 and RAC1 suppressed t(8,21) AML cell line Furthermore, nuclear import of RUNX1/ETO was aberrated following RUNX1/ETO and RAC1 suppression suggesting association in ROS control. A different picture was depicted in non t(8;21) cells where suppression of RAC1 and FLT3 led to decreased levels of FOXO3a and ROS. Results alltogether indicate a possible dysregulation of ROS levels by RUNX1/ETO in t(8,21) AML.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  15. Chan PF, Ang KP, Hamid RA
    J Biol Inorg Chem, 2024 Mar;29(2):217-241.
    PMID: 38369679 DOI: 10.1007/s00775-023-02041-x
    We previously reported that the bismuth(III) dithiocarbamate derivative, bismuth diethyldithiocarbamate (1) exhibited greater cytotoxicity while inducing apoptosis via the intrinsic pathway in MCF-7 cells. We further evaluated the other bismuth(III) dithiocarbamate derivatives, Bi[S2CNR]3, with R = (CH2CH2OH)(iPr), (CH2)4, and (CH2CH2OH)(CH3), denoted as 2, 3, and 4, respectively, in the same MCF-7 cell line. 2-4 were found to exhibit IC50 values of 10.33 ± 0.06 µM, 1.07 ± 0.01 µM and 25.37 ± 0.12 µM, respectively, compared to that of cisplatin at 30.53 ± 0.23 µM. Apoptotic promotion via the mitochondrial-dependent pathway was due to the elevation of intracellular reactive oxygen species (ROS), promotion of caspases, release of cytochrome c, fragmentation of DNA, and results of staining assay observed in all compound-treated cells. 2-4 are also capable of suppressing MCF-7 cell invasion and modulate Lys-48 also Lys-63 linked polyubiquitination, leading to proteasomal degradation. Analysis of gene expression via qRT-PCR revealed their modulation, which supported all activities conducted upon treatment with 2-4. Altogether, bismuth dithiocarbamate derivatives, with bismuth(III) as the metal center bound to ligands, isopropyl ethanol, pyrrolidine, and methyl ethanol dithiocarbamate, are potential anti-breast cancer agents that induce apoptosis and suppress metastasis. Further studies using other breast cancer cell lines and in vivo studies are recommended to clarify the anticancer effects of these compounds.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  16. Naes SM, Ab-Rahim S, Mazlan M, Syafruddin SE, Mohtar MA, Abuhamad AY, et al.
    PLoS One, 2025;20(8):e0329501.
    PMID: 40824957 DOI: 10.1371/journal.pone.0329501
    Although purine metabolism is one of the most impacted pathways in colorectal cancer (CRC), little is known about the role of equilibrative nucleoside transporter 2 (ENT2) in CRC development and its association with the altered purine metabolism pathway. This study aimed to determine the role of ENT2 in altered purine metabolism in the early and late stages of CRC using CRISPR/Cas9 gene editing tools and a variety of functional experiments. The expression of ENT2 was significantly higher (P oxygen species (ROS) level. These data suggest that the ENT2 KO elevated the ROS levels induced apoptosis and impaired the cell proliferation of the early stage of CRC cell line, i.e., HT29/KO clonal cells. In this context, targeting ENT2 gene might be a potential strategy in CRC treatment by increasing the production of ROS and hence, inducing the apoptosis pathway.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  17. Verma M, Fatima S, Syed A, Elgorban AM, Abid I, Wong LS, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2025 Aug;398(8):10379-10398.
    PMID: 39985578 DOI: 10.1007/s00210-025-03899-1
    Studies on the assessment of anticancer efficacy of plant-derived phytochemicals by targeting signaling pathways have drawn a lot of attention recently for human health. Multiple investigations have proposed an involvement of Notch pathway in the processes of cancer angiogenesis and metastasis, and drug resistance. Moreover, overexpression of Notch signaling is associated with increased prostate cancer (PrCa) cell growth and development. A number of chemotherapeutic agents are reported to become resistant over a period of time and have severe side effects. To increase efficacy and lessen drug-induced toxicity, a variety of bioactive compounds have been utilized alone or as adjuncts to traditional chemotherapy. Therefore, in the present study, the potential of AKBA in inhibiting the proliferation of PrCa cells by modulating Notch signaling components and its efficacy in combination with cisplatin was investigated. The results exhibited a substantial reduction in cell survival (IC50 = 25.28 µM at 24 h and 16.50 µM at 48 h) and cellular alterations in AKBA-treated PrCa cells. Additionally, AKBA caused nuclear condensation, increased reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, and caspase activation, ultimately leading to apoptosis in PrCa cells. Moreover, AKBA-elicited apoptosis was evidenced by an augmentation in the Bax to Bcl2 ratio. AKBA was also found to induce G0/G1 arrest which was substantiated by reduced cyclin D1 and CDK4 expression levels concomitantly with increased expression of p21 and p27 genes. Intriguingly, AKBA demonstrated significant downregulation of Notch signaling mediators. Furthermore, the isobolograms of the combination treatment indicated that AKBA has the potential to synergistically enhance the cytotoxic efficacy of cisplatin in DU145 cells, as evidenced by CI 
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  18. Hamid ZA, Tan HY, Chow PW, Harto KAW, Chan CY, Mohamed J
    Sultan Qaboos Univ Med J, 2018 May;18(2):e130-e136.
    PMID: 30210840 DOI: 10.18295/squmj.2018.18.02.002
    Objectives: The ex vivo maintenance of haematopoietic stem/progenitor cells (HSPCs) is crucial to ensure a sufficient supply of functional cells for research or therapeutic applications. However, when exposed to reactive oxygen species (ROS) in a normoxic microenvironment, HSPCs exhibit genomic instability which may diminish their quantity and quality. This study aimed to investigate the role of N-acetylcysteine (NAC) supplementation on the oxidative stress levels, genotoxicity and lineage commitment potential of murine haematopoietic stem/progenitor cells (HSPCs).

    Methods: This study was carried out at the Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia, between June 2016 and July 2017. Bone marrow cells were isolated from nine mice and cultured in a growth medium. Various concentrations of NAC between 0.125-2 μM were added to the culture for 48 hours; these cells were then compared to non-supplemented cells harvested from the remaining three mice as the control group. A trypan blue exclusion test was performed to determine cell viability, while intracellular ROS levels and genotoxicity were determined by hydroethidine staining and comet assay, respectively. The lineage commitment potential of erythroid, myeloid and pre-B-lymphoid progenitor cells was evaluated via colony-forming cell assay.

    Results: NAC supplementation at 0.25, 0.5 and 2 μM significantly increased cell viability (P <0.050), while intracellular ROS levels significantly decreased at 0.25 and 0.5 μM (P <0.050). Moreover, DNA damage was significantly reduced at all NAC concentrations (P <0.050). Finally, the potential lineage commitment of the cells was not significantly affected by NAC supplementation (P >0.050).

    Conclusion: The findings of this study indicate that NAC supplementation may potentially overcome the therapeutic limitations of ex vivo-maintained HSPCs.

    Matched MeSH terms: Reactive Oxygen Species/metabolism; Reactive Oxygen Species/toxicity
  19. Leong SW, Chia SL, Abas F, Yusoff K
    Eur J Med Chem, 2018 Sep 05;157:716-728.
    PMID: 30138803 DOI: 10.1016/j.ejmech.2018.08.039
    In the present study, a series of forty-five asymmetrical meta-methoxylated diarylpentanoids have been synthesized, characterized and evaluated for their in-vitro anti-cancer potential. Among the forty-five analogs, three compounds (20, 33 and 42) have been identified as lead compounds due to their excellent inhibition against five human cancer cell lines including SW620, A549, EJ28, HT1080 and MCF-7. Structure-activity relationship study on cytotoxicity of tested compounds suggested that the presence of meta-oxygenated phenyl ring played a critical role in enhancing their cytotoxic effects. Compounds 33 and 42 in particular, exhibited strongest cytotoxicity against tested cell lines with the IC50 values ranging from 1.1 to 4.3 μM. Subsequent colony formation assay on SW620 cell line showed that both compounds 33 and 42 possessed strong anti-proliferative activity. In addition, flow cytometry based experiments revealed that these compounds could trigger intracellular ROS production thus inducing G2/M-phase cell arrest and apoptosis. All these results suggested that poly meta-oxygenated diarylpentnoid is a promising scaffold which deserved further modification and investigation in the development of natural product-based anti-cancer drug.
    Matched MeSH terms: Reactive Oxygen Species/analysis; Reactive Oxygen Species/metabolism
  20. Darbandi M, Darbandi S, Agarwal A, Baskaran S, Dutta S, Sengupta P, et al.
    J Assist Reprod Genet, 2019 Feb;36(2):241-253.
    PMID: 30382470 DOI: 10.1007/s10815-018-1350-y
    PURPOSE: This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction.

    METHODS: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS 

    Matched MeSH terms: Reactive Oxygen Species/isolation & purification*; Reactive Oxygen Species/metabolism
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