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  1. Halder A, Jethwa M, Mukherjee P, Ghosh S, Das S, Helal Uddin ABM, et al.
    Artif Cells Nanomed Biotechnol, 2020 Nov 17;48(1):1362-1371.
    PMID: 33284038 DOI: 10.1080/21691401.2020.1850465
    Cancer management presents multifarious problems. Triple negative breast cancer (TNBC) is associated with inaccurate prognosis and limited chemotherapeutic options. Betulinic acid (BA) prevents angiogenesis and causes apoptosis of TNBC cells. NIH recommends BA for rapid access in cancer chemotherapy because of its cell-specific toxicity. BA however faces major challenges in therapeutic practices due to its limited solubility and cellular entree. We report lactoferrin (Lf) attached BA nanoparticles (Lf-BAnp) for rapid delivery in triple negative breast (MDA-MB-231) and laryngeal (HEp-2) cancer cell types. Lf association was confirmed by SDS-PAGE and FT-IR analysis. Average hydrodynamic size of Lf-BAnp was 147.7 ± 6.20 nm with ζ potential of -28.51 ± 3.52 mV. BA entrapment efficiency was 75.38 ± 2.70% and the release mechanism followed non-fickian pattern. Impact of Lf-BAnp on cell cycle and cytotoxicity of triple negative breast cancer and its metastatic site laryngeal cancer cell lines were analyzed. Lf-BAnp demonstrated strong anti-proliferative and cytotoxic effects, along with increased sub-G1 population and reduced number of cells in G1 and G2/M phases of the cell cycle, confirming reduced cell proliferation and significant cell death. Speedy intracellular entry of Lf-BAnp occurred within 30 min. Lf-BAnp design was explored for the first time as safer chemotherapeutic arsenals against complex TNBC conditions.
    Matched MeSH terms: Cell Survival/drug effects
  2. Chien SY, Hsu CH, Lin CC, Chuang YC, Lo YS, Hsi YT, et al.
    Environ Toxicol, 2017 Aug;32(8):2085-2092.
    PMID: 28383207 DOI: 10.1002/tox.22423
    Nasopharyngeal carcinoma (NPC), a tumor arising from epithelial cells that cover the surface and line the nasopharynx, is a rare malignancy worldwide but is prevalent in certain geographical areas, such as Southern Asia (Taiwan, Hong Kong, Singapore, Malaysia, and Southern China) and North Africa. Despite advances in diagnostic techniques and improvements in treatment modalities, the prognosis of NPC remains poor. Therefore, an effective chemotherapy regimen that enhances tumor sensitivity to chemotherapeutics is urgently required. Nimbolide, derived from Azadirachta indica, has a wide range of beneficial effects, including anti-inflammatory and anticancer properties. The present study evaluated the antitumor activity of nimbolide in NPC cells and its underlying mechanisms. Our results revealed that the treatment of HONE-1 cells with nimbolide potently inhibited cell viability. Moreover, nimbolide led to cell cycle arrest, which subsequently activated caspase-3, -8, and -9 and poly (ADP-ribose) polymerase to induce cell apoptosis. Moreover, nimbolide induced Bik, Bax, and t-Bid expression in HONE-1 cells. The results indicated that nimbolide induces apoptosis through the modulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways. Nimbolide induces apoptosis in human NPC cells and is a potential chemopreventive agent against NPC proliferation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2085-2092, 2017.
    Matched MeSH terms: Cell Survival/drug effects
  3. Jalalonmuhali M, Caroll R, Deayton S, Emery T, Humphreys I, Lim SJ, et al.
    Hum Immunol, 2020 Dec;81(12):679-684.
    PMID: 32736900 DOI: 10.1016/j.humimm.2020.07.005
    BACKGROUND: Angiotensin II type 1 receptor antibody (AT1R-Ab) is a non-HLA antibody that has been reported to cause antibody-mediated rejection and graft loss in kidney transplantation. The prevalence of positive AT1R-Ab varies between 8% and 18% in different regions. Thus, this study aims to determine the prevalence of AT1R-Ab among the Malaysian population.

    METHODOLOGY: All sera for AT1R-Ab were collected at the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The sera were centrifuged and kept refrigerated at -80 °C before being transported to the South Australian Transplantation and Immunogenetics Laboratory (SATIS). Enzyme-linked immunosorbent assay kit (One Lambda) was used for the detection of AT1R-Ab, and it was performed according to the manufacturer's instructions. The level of >17.1 U/mL was considered to be AT1R-Ab positive; 10.0-17.1 U/mL at risk, and <10.0 U/mL negative.

    RESULTS: A total of 115 samples were collected from 99 patients pre and post-kidney transplant recipients. From the pre-transplant sera (n = 68) 17.7% were positive, 35.3% were at risk and 47.0% were negative. The positive AT1R-Ab cohort were relatively younger, with a mean age of 34.7 ± 8.3 years old and statistically significant, with a p-value of 0.028. Among the sera that were tested positive, 19.0% were from the Chinese ethnicity, 6.7% from Malay and 16.7% from Indian. There was no difference in the rejection episodes, persistent or de novo HLA-DSA, and graft function between the group (AT1R-Ab negative vs AT1R-Ab at risk and positive) and the results were consistent in a model adjusted for all potential confounders.

    CONCLUSION: The prevalence of positive (>17.1 U/mL) pre-transplant AT1R-Ab was 17.7% and 35.3% were at risk (10.0-17.1 U/mL) in our pre-transplant cohort.

    Matched MeSH terms: Graft Survival/immunology*
  4. Eh Suk VR, Chung I, Misran M
    Curr Drug Deliv, 2020;17(4):292-302.
    PMID: 32039684 DOI: 10.2174/1567201817666200210122933
    BACKGROUND: Liposomes are mostly known to be prepared from phospholipids and lipids and have a remarkable capacity to encapsulate both lipophobic and lipophilic molecules. However, there is little research on developing fatty acid liposomes for chemotherapy.

    OBJECTIVE: We have successfully prepared mixed fatty acid liposomes from two monounsaturated fatty acids, namely oleic acid and erucic acid, which stabilised by DOPEPEG2000. The Critical Vesicular Concentration (CVC) of liposomes was found to be within 0.09 to 0.21 mmol dm-3, with an average particle size of 400 nm.

    METHODS: Encapsulation of various anticancer drugs such as folinic acid, methotrexate, doxorubicin, or irinotecan resulted in Encapsulation Efficiency (%EE) of up to 90%. Using a 3-(4, 5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the median Inhibitory Concentration (IC50) values of mixed oleic acid-erucic acid encapsulating hydrophilic drugs was remarkably reduced at the end of 24 hours of incubation with the human lung carcinoma cell line A549.

    RESULTS: The results suggest that mixed oleic acid-erucic acid liposomes are a potential new approach to further develop as an alternative vehicle of various drugs for cancer treatment.

    Matched MeSH terms: Cell Survival/drug effects
  5. Jeyamogan S, Khan NA, Sagathevan K, Siddiqui R
    Anticancer Agents Med Chem, 2020;20(13):1558-1570.
    PMID: 32364082 DOI: 10.2174/1871520620666200504103056
    BACKGROUND: Cancer contributes to significant morbidity and mortality despite advances in treatment and supportive care. There is a need for the identification of effective anticancer agents. Reptiles such as tortoise, python, and water monitor lizards are exposed to heavy metals, tolerate high levels of radiation, feed on rotten/germ-infested feed, thrive in unsanitary habitat and yet have prolonged lifespans. Such species are rarely reported to develop cancer, suggesting the presence of anticancer molecules/mechanisms.

    METHODS: Here, we tested effects from sera of Asian water monitor lizard (Varanus salvator), python (Malayopython reticulatus) and tortoise (Cuora kamaroma amboinensis) against cancer cells. Sera were collected and cytotoxicity assays were performed using prostate cancer cells (PC3), Henrietta Lacks cervical adenocarcinoma cells (HeLa) and human breast adenocarcinoma cells (MCF7), as well as human keratinized skin cells (Hacat), by measuring lactate dehydrogenase release as an indicator for cell death. Growth inhibition assays were performed to determine the effects on cancer cell proliferation. Liquid chromatography mass spectrometry was performed for molecular identification.

    RESULTS: The findings revealed that reptilian sera, but not bovine serum, abolished viability of Hela, PC3 and MCF7 cells. Samples were subjected to liquid chromatography mass spectrometry, which detected 57 molecules from V. salvator, 81 molecules from Malayopython reticulatus and 33 molecules from C. kamaroma amboinensis and putatively identified 9 molecules from V. salvator, 20 molecules from Malayopython reticulatus and 9 molecules from C. kamaroma amboinensis when matched against METLIN database. Based on peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition, 123 potential Anticancer Peptides (ACPs) were identified from 883 peptides from V. salvator, 306 potential ACPs from 1074 peptides from Malayopython reticulatus and 235 potential ACPs from 885 peptides from C. kamaroma amboinensis.

    CONCLUSION: To our knowledge, for the first time, we reported comprehensive analyses of selected reptiles' sera using liquid chromatography mass spectrometry, leading to the identification of potentially novel anticancer agents. We hope that the discovery of molecules from these animals will pave the way for the rational development of new anticancer agents.

    Matched MeSH terms: Cell Survival/drug effects
  6. Abuelizz HA, Anouar EH, Marzouk M, Hasan MH, Saleh SR, Ahudhaif A, et al.
    Anticancer Agents Med Chem, 2020;20(14):1714-1721.
    PMID: 32593283 DOI: 10.2174/1871520620666200627212128
    BACKGROUND: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies.

    OBJECTIVE: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines.

    METHODS: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets.

    RESULTS: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase.

    CONCLUSION: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

    Matched MeSH terms: Cell Survival/drug effects
  7. Bera H, Abbasi YF, Gajbhiye V, Ping LL, Salve R, Kumar P, et al.
    Int J Biol Macromol, 2021 Jun 30;181:169-179.
    PMID: 33775757 DOI: 10.1016/j.ijbiomac.2021.03.152
    Curdlan (CN)-doped montmorillonite/poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide) [CN/MT/P(NIPA-co-MBA)] smart nanocomposites (NCs) were developed for efficient erlotinib HCl (ERL) delivery to lung cancer cells. The placebo NCs demonstrated excellent biodegradability, pH/thermo-responsive swelling profiles and declined molar mass (M¯c) between the crosslinks with increasing temperature. The XRD, FTIR, DSC, TGA, and SEM analyses revealed the architectural chemistry of these NC scaffolds. The NCs loaded with ERL (F-1-F-3) displayed acceptable diameter (734-1120 nm) and zeta potential (+1.16 to -11.17 mV), outstanding drug entrapping capability (DEE, 78-99%) and sustained biphasic ERL elution patterns (Q8h, 53-91%). The ERL release kinetics of the optimal matrices (F-3) obeyed Higuchi model and their transport occurred through anomalous diffusion. The mucin adsorption behaviour of these matrices followed Freudlich isotherms. As compared to pure ERL, the formulation (F-3) displayed an improved anti-proliferative potential and induced apoptosis more effectively on A549 cells. Thus, the CN-doped smart NCs could be utilized as promising drug-cargoes for lung cancer therapy.
    Matched MeSH terms: Cell Survival/drug effects
  8. Mahmood RI, Abbass AK, Razali N, Al-Saffar AZ, Al-Obaidi JR
    Int J Biol Macromol, 2021 Aug 01;184:636-647.
    PMID: 34174302 DOI: 10.1016/j.ijbiomac.2021.06.144
    The second most predominant cancer in the world and the first among women is breast cancer. We aimed to study the protein abundance profiles induced by lectin purified from the Agaricus bisporus mushroom (ABL) and conjugated with CaCO3NPs in the MCF-7 breast cancer cell line. Two-dimensional electrophoresis (2-DE) and orbitrap mass spectrometry techniques were used to reveal the protein abundance pattern induced by lectin. Flow cytometric analysis showed the accumulation of ABL-CaCO3NPs treated cells in the G1 phase than the positive control. Thirteen proteins were found different in their abundance in breast cancer cells after 24 h exposure to lectin conjugated with CaCO3NPs. Most of the identified proteins were showing a low abundance in ABL-CaCO3NPs treated cells in comparison to the positive and negative controls, including V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP. Hornerin, tropomyosin alpha-1 chain, annexin A2, and protein disulfide-isomerase were up-regulated in comparison to the positive. Bioinformatic analyses revealed the regulation changes of these proteins mainly affected the pathways of 'Bcl-2-associated athanogene 2 signalling pathway', 'Unfolded protein response', 'Caveolar-mediated endocytosis signalling', 'Clathrin-mediated endocytosis signalling', 'Calcium signalling' and 'Sucrose degradation V', which are associated with breast cancer. We concluded that lectin altered the abundance in molecular chaperones/heat shock proteins, cytoskeletal, and metabolic proteins. Additionally, lectin induced a low abundance of MCF-7 cancer cell proteins in comparison to the positive and negative controls, including; V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP.
    Matched MeSH terms: Cell Survival/drug effects
  9. Solanki N, Mehta M, Chellappan DK, Gupta G, Hansbro NG, Tambuwala MM, et al.
    Future Med Chem, 2020 11;12(22):2019-2034.
    PMID: 33124483 DOI: 10.4155/fmc-2020-0083
    Aim: In the present study boswellic acids-loaded chitosan nanoparticles were synthesized using ionic gelation technique. The influence of independent variables were studied and optimized on dependent variables using central composite design. Methodology & results: The designed nanoparticles were observed spherical in shape with an average size of 67.5-187.2 nm and have also shown an excellent entrapment efficiency (80.06 ± 0.48). The cytotoxicity assay revealed enhanced cytotoxicity for drug-loaded nanoparticles in contrast to the free drug having an IC50 value of 17.29 and 29.59 μM, respectively. Flow cytometry confirmed that treatment of cells with 40 μg/ml had arrested 22.75 ± 0.3% at SubG0 phase of the cell cycle when compared with untreated A459 cells. The observed results justified the boswellic acids-loaded chitosan nanoparticles were effective due to greater cellular uptake, sustained intercellular drug retention and enhanced antiproliferative effect by inducing apoptosis.
    Matched MeSH terms: Cell Survival/drug effects
  10. Hiu JJ, Yap MKK
    Int J Biol Macromol, 2021 Aug 01;184:776-786.
    PMID: 34174307 DOI: 10.1016/j.ijbiomac.2021.06.145
    Naja sumatrana venom cytotoxin (sumaCTX) is a basic protein which belongs to three-finger toxin family. It has been shown to induce caspase-dependent, mitochondrial-mediated apoptosis in MCF-7 cells at lower concentrations. This study aimed to investigate the alteration of secretome in MCF-7 cells following membrane permeabilization by high concentrations of sumaCTX, using label-free quantitative (LFQ) approach. The degree of membrane permeabilization of sumaCTX was determined by lactate dehydrogenase (LDH) assay and calcein-propidium iodide (PI) assays. LDH and calcein-PI assays revealed time-dependent membrane permeabilization within a narrow concentration range. However, as toxin concentrations increased, prolonged exposure of MCF-7 cells to sumaCTX did not promote the progression of membrane permeabilization. The secretome analyses showed that membrane permeabilization was an event preceding the release of intracellular proteins. Bioinformatics analyses of the LFQ secretome revealed the presence of 105 significantly distinguished proteins involved in metabolism, structural supports, inflammatory responses, and necroptosis in MCF-7 cells treated with 29.8 μg/mL of sumaCTX. Necroptosis was presumably an initial stress response in MCF-7 cells when exposed to high sumaCTX concentration. Collectively, sumaCTX-induced the loss of membrane integrity in a concentration-dependent manner, whereby the cell death pattern of MCF-7 cells transformed from apoptosis to necroptosis with increasing toxin concentrations.
    Matched MeSH terms: Cell Survival/drug effects
  11. Khaw KY, Kumar P, Yusof SR, Ramanathan S, Murugaiyah V
    Arch Pharm (Weinheim), 2020 Nov;353(11):e2000156.
    PMID: 32716578 DOI: 10.1002/ardp.202000156
    α-Mangostin has been reported to possess a broad range of pharmacological effects including potent cholinesterase inhibition, but the development of α-mangostin as a potential lead compound is impeded by its toxicity. The present study investigated the impact of simple structural modification of α-mangostin on its cholinesterase inhibitory activities and toxicity toward neuroblastoma and liver cancer cells. The dialkylated derivatives retained good acetylcholinesterase (AChE) inhibitory activities with IC50 values between 4.15 and 6.73 µM, but not butyrylcholinesterase (BChE) inhibitory activities, compared with α-mangostin, a dual inhibitor (IC50 : AChE, 2.48 µM; BChE, 5.87 µM). Dialkylation of α-mangostin produced AChE selective inhibitors that formed hydrophobic interactions at the active site of AChE. Interestingly, all four dialkylated derivatives of α-mangostin showed much lower cytotoxicity, being 6.4- to 9.0-fold and 3.8- to 5.5-fold less toxic than their parent compound on neuroblastoma and liver cancer cells, respectively. Likewise, their selectivity index was higher by 1.9- to 4.4-fold; in particular, A2 and A4 showed improved selectivity index compared with α-mangostin. Taken together, modification of the hydroxyl groups of α-mangostin at positions C-3 and C-6 greatly influenced its BChE inhibitory and cytotoxic but not its AChE inhibitory activities. These dialkylated derivatives are viable candidates for further structural modification and refinement, worthy in the search of new AChE inhibitors with higher safety margins.
    Matched MeSH terms: Cell Survival/drug effects
  12. Mohd Amin AT, Zaki RA, Friedmacher F, Sharif SP
    Pediatr Surg Int, 2021 Jul;37(7):881-886.
    PMID: 33779823 DOI: 10.1007/s00383-021-04879-1
    PURPOSE: The role of hypoalbuminemia and raised C-reactive protein (CRP) levels in predicting critical prognosis has been described extensively in adult literature. However, there are limited studies in pediatrics, particularly neonates. The CRP/albumin (CRP/ALB) ratio is often associated with higher mortality, organ failure and prolonged hospital stay. We hypothesized that the serum CRP/ALB ratio has a prognostic value in predicting surgery and mortality in neonates with necrotizing enterocolitis (NEC).

    METHODS: Retrospective review of all neonates with clinical and radiological evidence of non-perforated NEC that were treated in a tertiary-level referral hospital between 2009 and 2018. General patient demographics, laboratory parameters and outcomes were recorded. Receiver operating characteristics analysis was performed to evaluated optimal cut-offs and area under the curve (AUC) with 95% confidence intervals (CI).

    RESULTS: A total of 191 neonates were identified. Of these, 103 (53.9%) were born at ≤ 28 weeks of gestation and 101 (52.9%) had a birth weight of ≤ 1000 g. Eighty-four (44.0%) patients underwent surgical intervention for NEC. The overall survival rate was 161/191 (84.3%). A CRP/ALB ratio of ≥ 3 on day 2 of NEC diagnosis was associated with a statistically significant higher likelihood for surgery [AUC 0.71 (95% CI 0.63-0.79); p 

    Matched MeSH terms: Survival Rate/trends
  13. Hamzah N, Safuan S, Wan Ishak WR
    Molecules, 2021 Jun 16;26(12).
    PMID: 34208534 DOI: 10.3390/molecules26123665
    Endothelial cell dysfunction is considered to be one of the major causes of vascular complications in diabetes. Polyphenols are known as potent antioxidants that can contribute to the prevention of diabetes. Corn silk has been reported to contain polyphenols and has been used in folk medicine in China for the treatment of diabetes. The present study aims to investigate the potential protective role of the phenolic-rich fraction of corn silk (PRF) against injuries to vascular endothelial cells under high glucose conditions in vitro and in vivo. The protective effect of PRF from high glucose toxicity was investigated using human umbilical vein endothelial cells (HUVECs). The protective effect of PRF was subsequently evaluated by using in vivo methods in streptozotocin (STZ)-induced diabetic rats. Results showed that the PRF significantly reduced the cytotoxicity of glucose by restoring cell viability in a dose-dependent manner. PRF was also able to prevent the histological changes in the aorta of STZ-induced diabetic rats. Results suggested that PRF might have a beneficial effect on diabetic patients and may help to prevent the development and progression of diabetic complications such as diabetic nephropathy and atherosclerosis.
    Matched MeSH terms: Cell Survival/drug effects
  14. Rothan HA, Zulqarnain M, Ammar YA, Tan EC, Rahman NA, Yusof R
    Trop Biomed, 2014 Jun;31(2):286-96.
    PMID: 25134897 MyJurnal
    Dengue virus infects millions of people worldwide and there is no vaccine or anti-dengue therapeutic available. Screening large numbers of medicinal plants for anti-dengue activities is an alternative strategy in order to find the potent therapeutic compounds. Therefore, this study was designed to identify anti-dengue activities in nineteen medicinal plant extracts that are used in traditional medicine. Local medicinal plants Vernonia cinerea, Hemigraphis reptans, Hedyotis auricularia, Laurentia longiflora, Tridax procumbers and Senna angustifolia were used in this study. The highest inhibitory activates against dengue NS2B-NS3pro was observed in ethanolic extract of S. angustifolia leaves, methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems. These findings were further verified by in vitro viral inhibition assay. Methanolic extract of V. cinerea leaves, ethanol extract of T. procumbens stems and at less extent ethanolic extract of S. angustifolia leaves were able to maintain the normal morphology of DENV2-infected Vero cells without causing much cytopathic effects (CPE). The percentage of viral inhibition of V. cinerea and T. procumbens extracts were significantly higher than S. angustifolia extract as measured by plaque formation assay and RT-qPCR. In conclusion, The outcome of this study showed that the methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems possessed high inhibitory activates against dengue virus that worth more investigation.
    Matched MeSH terms: Cell Survival/drug effects
  15. Rothan HA, Buckle MJ, Ammar YA, Mohammadjavad P, Shatrah O, Noorsaadah AR, et al.
    Trop Biomed, 2013 Dec;30(4):681-90.
    PMID: 24522138
    Various clinical symptoms are caused by dengue virus ranging from mild fever to severe hemorrhagic fever while there is no successful anti-dengue therapeutics available. Among different strategies towards identifying and developing anti-dengue therapeutics, testing anti-dengue properties of known drugs could represent an efficient strategy for which information of its medical approval, toxicity and side effects is readily available. In this study, we evaluated the antiviral activity of some medical compounds towards dengue NS2B-NS3 protease (DENV2 NS2B-NS3pro) as a target to inhibit dengue virus replication. Mefenamic acid, a non-steroid anti inflammatory drug and doxycycline, a derivative antibiotic of tetracycline both showed significant inhibition potential against DENV2 NS2B-NS3pro Ki values 32 ± 2 μM and 55 ± 5 μM respectively. The effective cytotoxic concentrations of 50% (CC50) against Vero cells were evaluated for mefenamic acid (150 ± 5 μM) and doxycycline (125 ± 4 μM). Concentrations lower than CC50 were used to test the inhibition potential of these compounds against DENV2 replication in Vero cells. The results showed significant reduction in viral load after applying mefenamic acid and doxycyline in concentration dependent manner. Mefenamic acid reduced viral RNA at EC50 of 32 ± 4 μM whilst doxycycline EC50 was 40 ± 3 μM. Mefenamic acid showed higher selectivity against dengue virus replication in vitro compared to doxycycline. These findings underline the need for further experimental and clinical studies on these drugs utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue infection.
    Matched MeSH terms: Cell Survival/drug effects
  16. Muhd Haffiz J, Norhayati I, Getha K, Nor Azah MA, Mohd Ilham A, Lili Sahira H, et al.
    Trop Biomed, 2013 Mar;30(1):9-14.
    PMID: 23665703 MyJurnal
    Essential oil from Cymbopogon nardus was evaluated for activity against Trypanosoma brucei brucei BS221 (IC50 = 0.31 ± 0.03 μg/mL) and cytotoxic effect on normal kidney (Vero) cells (IC50 = >100 μg/mL). The crude essential oil was subjected to various chromatography techniques afforded active sub fractions with antitrypanosomal activity; F4 (IC50 = 0.61 ± 0.06 μg/mL), F6 (IC50= 0.73 ± 0.33 μg/mL), F7 (IC50 = 1.15 ± 0 μg/mL) and F8 (IC50 = 1.11 ± 0.01 μg/mL). These active fractions did not exhibit any toxic effects against Vero cell lines and the chemical profiles investigation indicated presence of α-and γ-eudesmol, elemol, α-cadinol and eugenol by GC/MS analysis.
    Matched MeSH terms: Cell Survival/drug effects
  17. Ilyas S, Tabasum R, Iftikhar A, Nazir M, Hussain A, Hussain A, et al.
    Sci Rep, 2021 01 18;11(1):1708.
    PMID: 33462261 DOI: 10.1038/s41598-020-80579-5
    Ifosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors. However, nephro, hepato, neuro cardio, and hematological toxicities associated with ifosfamide render its use limited. These side effects could range from organ failure to life-threatening situations. The present study aimed to evaluate the attenuating efficiency of Berberis vulgaris root extract (BvRE), a potent nephroprotective, hepatoprotective, and lipid-lowering agent, against ifosfamide-induced toxicities. The study design comprised eight groups of Swiss albino rats to assess different dose regimes of BvRE and ifosfamide. Biochemical analysis of serum (serum albumin, blood urea nitrogen, creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, and triglycerides) along with complete blood count was performed. Kidney, liver, brain, and heart tissue homogenates were used to find malondialdehyde, catalase, and glutathione S-transferase levels in addition to the acetylcholinesterase of brain tissue. The results were further validated with the help of the histopathology of the selected organs. HeLa cells were used to assess the effect of BvRE on ifosfamide cytotoxicity in MTT assay. The results revealed that pre- and post-treatment regimens of BvRE, as well as the combination therapy exhibited marked protective effects against ifosfamide-induced nephro, hepato, neuro, and cardiotoxicity. Moreover, ifosfamide depicted a synergistic in vitro cytotoxic effect on HeLa cells in the presence of BvRE. These results corroborate that the combination therapy of ifosfamide with BvRE in cancer treatment can potentiate the anticancer effects of ifosfamide along with the amelioration of its conspicuous side effects.
    Matched MeSH terms: Cell Survival/drug effects
  18. Kiew LV, Cheong SK, Sidik K, Chung LY
    Int J Pharm, 2010 May 31;391(1-2):212-20.
    PMID: 20214970 DOI: 10.1016/j.ijpharm.2010.03.010
    To enhance the stability of the anticancer drug gemcitabine (2'-deoxy-2',2'-difluorocytidine), it was conjugated to poly-l-glutamic acid (PG-H) via a carbodiimide reaction. The synthesised poly-l-glutamic acid-gemcitabine (PG-G) was purified and characterised by using SDS-PAGE to estimate its molecular weight, HPLC to determine its purity and degree of drug loading, and NMR to elucidate the structure. In vitro aqueous hydrolytic studies showed that the gemcitabine release from the polymeric drug conjugate was pH dependent, and that the conjugation to PG-H improved its stability in human plasma. The release of the bound gemcitabine from PG-G in plasma was mediated by a hydrolytic process. It began with a lag phase, followed by linear release between 12 and 48h, and reached equilibrium at 72h with 51% of the gemcitabine released. In vitro cytotoxicity studies using MCF-7 and MDA-MB-231 human mammary cancer cells, as well as human dermal fibroblasts (HDF), showed that PG-G displayed a lower dose dependent cytotoxic effect with respect to the parent drug gemcitabine. On the other hand, in 4T1 mouse mammary tumour cells, PG-G and gemcitabine showed similar toxicities. Gemcitabine was more than likely released hydrolytically from PG-G and taken up by MCF-7, MDA-MB-231 and HDF, whereas both released gemcitabine and PG-G were taken up by 4T1 to mediate the observed cytotoxicities. The improved stability and extended sustained release profile may render PG-G a potential anticancer prodrug.
    Matched MeSH terms: Cell Survival/drug effects
  19. Ploos van Amstel S, Noordzij M, Borzych-Duzalka D, Chesnaye NC, Xu H, Rees L, et al.
    Am J Kidney Dis, 2021 09;78(3):380-390.
    PMID: 33549627 DOI: 10.1053/j.ajkd.2020.11.031
    RATIONALE & OBJECTIVE: Research on pediatric kidney replacement therapy (KRT) has primarily focused on Europe and North America. In this study, we describe the mortality risk of children treated with maintenance peritoneal dialysis (MPD) in different parts of the world and characterize the associated demographic and macroeconomic factors.

    STUDY DESIGN: Prospective cohort study.

    SETTING & PARTICIPANTS: Patients younger than 19 years at inclusion into the International Pediatric Peritoneal Dialysis Network registry, who initiated MPD between 1996 and 2017.

    EXPOSURE: Region as primary exposure (Asia, Western Europe, Eastern Europe, Latin America, North America, and Oceania). Other demographic, clinical, and macroeconomic (4 income groups based on gross national income) factors also were studied.

    OUTCOME: All-cause MPD mortality.

    ANALYTICAL APPROACH: Patients were observed for 3 years, and the mortality rates in different regions and income groups were calculated. Cause-specific hazards models with random effects were fit to calculate the proportional change in variance for factors that could explain variation in mortality rates.

    RESULTS: A total of 2,956 patients with a median age of 7.8 years at the start of KRT were included. After 3 years, the overall probability of death was 5%, ranging from 2% in North America to 9% in Eastern Europe. Mortality rates were higher in low-income countries than in high-income countries. Income category explained 50.1% of the variance in mortality risk between regions. Other explanatory factors included peritoneal dialysis modality at start (22.5%) and body mass index (11.1%).

    LIMITATIONS: The interpretation of interregional survival differences as found in this study may be hampered by selection bias.

    CONCLUSIONS: This study shows that the overall 3-year patient survival on pediatric MPD is high, and that country income is associated with patient survival.

    Matched MeSH terms: Survival Rate/trends
  20. Muthuraju S, Pati S, Rafiqul M, Abdullah JM, Jaafar H
    J Biosci, 2013 Mar;38(1):93-103.
    PMID: 23385817
    Traumatic brain injury (TBI) causes significant mortality in most developing countries worldwide. At present, it is imperative to identify a treatment to address the devastating post-TBI consequences. Therefore, the present study has been performed to assess the specific effect of immediate exposure to normabaric hyperoxia (NBO) after fluid percussion injury (FPI) in the striatum of mice. To execute FPI, mice were anesthetised and sorted into (i) a TBI group, (ii) a sham group without injury and (iii) a TBI group treated with immediate exposure to NBO for 3 h. Afterwards, brains were harvested for morphological assessment. The results revealed no changes in morphological and neuronal damage in the sham group as compared to the TBI group. Conversely, the TBI group showed severe morphological changes as well as neuronal damage as compared to the TBI group exposed to NBO for 3 h. Interestingly, our findings also suggested that NBO treatment could diminish the neuronal damage in the striatum of mice after FPI. Neuronal damage was evaluated at different points of injury and the neighbouring areas using morphology, neuronal apoptotic cell death and pan-neuronal markers to determine the complete neuronal structure. In conclusion, immediate exposure to NBO following FPI could be a potential therapeutic approach to reduce neuronal damage in the TBI model.
    Matched MeSH terms: Cell Survival/drug effects
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