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  1. Fulltext Optimization of brush-like cationic copolymers for nonviral gene delivery
    Wei H, Pahang JA, Pun SH
    Biomacromolecules, 2013 Jan 14;14(1):275-84.
    PMID: 23240866 DOI: 10.1021/bm301747r
    Polyethylenimine (PEI) is one of the most broadly used polycations for gene delivery due to its high transfection efficiency and commercial availability but materials are cytotoxic and often polydisperse. The goal of current work is to develop an alternative family of polycations based on controlled living radical polymerization (CLRP) and to optimize the polymer structure for efficient gene delivery. In this study, well-defined poly(glycidyl methacrylate)(P(GMA)) homopolymers were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization followed by decoration using three different types of oligoamines, i.e., tetraethylenepentamine (TEPA), pentaethylenehexamine (PEHA), and tris(2-aminoethyl)amine (TREN), respectively, to generate various P(GMA-oligoamine) homopolycations. The effect of P(GMA) backbone length and structure of oligoamine on gene transfer efficiency was then determined. The optimal polymer, P(GMA-TEPA)(50), provided comparable transfection efficiency but lower cytotoxicity than PEI. P(GMA-TEPA)(50) was then used as the cationic block in diblock copolymers containing hydrophilic N-(2-hydroxypropyl) methacrylamide (HPMA) and oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA). Polyplexes of block copolymers were stable against aggregation in physiological salt condition and in Opti-MEM due to the shielding effect of P(HPMA) and P(OEGMA). However, the presence of the HPMA/OEGMA block significantly decreased the transfection efficacy of P(GMA-TEPA)(50) homopolycation. To compensate for reduced cell uptake caused by the hydrophilic shell of polyplex, the integrin-binding peptide, RGD, was conjugated to the hydrophilic chain end of P(OEGMA)(15)-b-P(GMA-TEPA)(50) copolymer by Michael-type addition reaction. At low polymer to DNA ratios, the RGD-functionalized polymer showed increased gene delivery efficiency to HeLa cells compared to analogous polymers lacking RGD.
    Matched MeSH terms: HeLa Cells
  2. Fulltext Tocotrienols and breast cancer: the evidence to date
    Nesaretnam K, Meganathan P, Veerasenan SD, Selvaduray KR
    Genes Nutr, 2012 Jan;7(1):3-9.
    PMID: 21516480 DOI: 10.1007/s12263-011-0224-z
    Breast cancer is the second most frequent cancer affecting women worldwide after lung cancer. The toxicity factor associated with synthetic drugs has turned the attention toward natural compounds as the primary focus of interest as anticancer agents. Vitamin E derivatives consisting of the well-established tocopherols and their analogs namely tocotrienols have been extensively studied due to their remarkable biological properties. While tocopherols have failed to offer protection, tocotrienols, in particular, α-, δ-, and γ-tocotrienols alone and in combination have demonstrated anticancer properties. The discovery of the antiangiogenic, antiproliferative, and apoptotic effects of tocotrienols, as well as their role as an inducer of immunological functions, not only reveals a new horizon as a potent antitumor agent but also reinforces the notion that tocotrienols are indeed more than antioxidants. On the basis of a transcriptomic platform, we have recently demonstrated a novel mechanism for tocotrienol activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicate a high affinity of specific forms of tocotrienols for ERβ, but not for ERα. Moreover, we have demonstrated that specific tocotrienols increase ERβ translocation into the nucleus which, in turn, activates the expression of estrogen-responsive genes (MIC-1, EGR-1 and Cathepsin D) in breast cancer cells only expressing ERβ cells (MDA-MB-231) and in cells expressing both ER isoforms (MCF-7). The binding of specific tocotrienol forms to ERβ is associated with the alteration of cell morphology, caspase-3 activation, DNA fragmentation, and apoptosis. Furthermore, a recently concluded clinical trial seems to suggest that tocotrienols in combination with tamoxifen may have the potential to extend breast cancer-specific survival.
    Matched MeSH terms: MCF-7 Cells
  3. Fulltext Gene expression profiles in human HepG2 cells treated with extracts of the Tamarindus indica fruit pulp
    Razali N, Aziz AA, Junit SM
    Genes Nutr, 2010 Dec;5(4):331-41.
    PMID: 21189869 DOI: 10.1007/s12263-010-0187-5
    Tamarindus indicaL. (T. indica) or locally known as asam jawa belongs to the family of Leguminosae. The fruit pulp had been reported to have antioxidant activities and possess hypolipidaemic effects. In this study, we attempted to investigate the gene expression patterns in human hepatoma HepG2 cell line in response to treatment with low concentration of the fruit pulp extracts. Microarray analysis using Affymetrix Human Genome 1.0 S.T arrays was used in the study. Microarray data were validated using semi-quantitative RT-PCR and real-time RT-PCR. Amongst the significantly up-regulated genes were those that code for the metallothioneins (MT1M, MT1F, MT1X) and glutathione S-transferases (GSTA1, GSTA2, GST02) that are involved in stress response. APOA4, APOA5, ABCG5 and MTTP genes were also significantly regulated that could be linked to hypolipidaemic activities of the T. indica fruit pulp.
    Matched MeSH terms: Hep G2 Cells
  4. Identification of Nasal Irrigation Bottle Contamination in Post Sinonasal Surgery
    Zahedi FD, Asmi NH, Husain S, Gendeh BS
    Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 3):1837-1842.
    PMID: 31763256 DOI: 10.1007/s12070-017-1219-x
    Nasal irrigation is an effective and cheap method in managing post sinonasal surgery patients. It works by improving ciliary clearance and performing mechanical debridement of the thick crust, decreasing mucosal edema and reducing the inflammatory mediators. Presence of nasal irrigation bottle contamination and its effect on patients have been studied. The aim of this study is to prospectively identify the risk of contamination in the nasal irrigation bottle, fluid from the bottle and to correlate with endoscopic findings from the patients who had underwent sinonasal surgery. Swabs will be taken from the nasal irrigation bottle and patient's middle meatus before the surgery and at each post surgery visits (2 and 4 weeks). Patients will be advised to irrigate their nose three times per day post sinonasal surgery. During endoscopic examination of the patient's nasal cavity at 2 and 4 weeks, any evidence of infection will be noted and documented. Additionally, a swab of fluid irrigated from the nasal cavity collected during the clinic follow-ups will also be taken. The specimens will be sent to the Microbiology laboratory for standard culture and sensitivity test. A total of 27 patients completed the study and were divided into case (n = 15) and control (n = 12) groups. The CFU (colony-forming unit) value of the bacteria cultured from the nasal cavity and the nasal irrigation bottle was statistically significantly (P = 0.00) increased from the baseline to the second week follow-up in both groups but not from the second week to the fourth week follow-up. The majority of the swabs from the nasal cavity of the patients and the nasal irrigation bottles were positively cultured for Pseudomonas sp. group. Other groups of bacteria that were cultured were Enterobacter sp., Coagulase Negative Staphylococcus (CONS) and Klebsiella sp. Endoscopically, there was no clinical evidence of infection found in the nasal cavity of the patients. The nasal irrigation bottle that was used in the post sinonasal surgery treatment and for alleviation of symptoms of sinonasal diseases was found to have bacterial contamination from the swabs taken from the bottle. However, despite this finding there was not clinical evidence of infection noted from the nasal endoscopic examination. A simple and effective method of cleaning the bottle would be helpful to reduce the bacterial contamination for this useful treatment method.
    Matched MeSH terms: Stem Cells
  5. Fulltext Boldine improves endothelial function in diabetic db/db mice through inhibition of angiotensin II-mediated BMP4-oxidative stress cascade
    Lau YS, Tian XY, Mustafa MR, Murugan D, Liu J, Zhang Y, et al.
    Br J Pharmacol, 2013 Nov;170(6):1190-8.
    PMID: 23992296 DOI: 10.1111/bph.12350
    Boldine is a potent natural antioxidant present in the leaves and bark of the Chilean boldo tree. Here we assessed the protective effects of boldine on endothelium in a range of models of diabetes, ex vivo and in vitro.
    Matched MeSH terms: Cells, Cultured; Endothelial Cells/drug effects; Endothelial Cells/metabolism
  6. Fulltext Phytochemical Constituents, Antioxidant and Antiproliferative Properties of a Liverwort, Lepidozia borneensis Stephani from Mount Kinabalu, Sabah, Malaysia
    Abu Bakar MF, Abdul Karim F, Suleiman M, Isha A, Rahmat A
    Evid Based Complement Alternat Med, 2015;2015:936215.
    PMID: 26640502 DOI: 10.1155/2015/936215
    The study aimed to investigate the phytochemical contents, antioxidant and antiproliferative activity of 80% methanol extract of Lepidozia borneensis. The total phenolic and total flavonoid contents were analysed using Folin-Ciocalteu and aluminium chloride colorimetric methods. Antioxidant properties were evaluated by using FRAP, ABTS, and DPPH assays while the effects of L. borneensis on the proliferation of MCF-7 cell line were evaluated by using MTT assay. The results showed that the total phenolic and flavonoid contents were 12.42 ± 0.47 mg GAE/g and 9.36 ± 1.29 mg CE/g, respectively. The GC-MS analysis revealed the presence of at least 35 compounds. The extract was found to induce cytotoxicity against MCF-7 cell line with IC50 value of 47.33 ± 7.37 µg/mL. Cell cycle analysis showed that the extract induced significant arrest at G0/G1 at 24 hours of treatment. After 72 hours of treatment, the proportion of cells in G0/G1 and G2-M phases had decreased significantly as compared to their control. Apoptosis occurred during the first 24 hours and significantly increased to 30.8% after 72 hours of treatment. No activation of caspase 3 was observed. These findings suggest that L. borneensis extract has the potential as natural antioxidant and anticancer agents.
    Matched MeSH terms: MCF-7 Cells
  7. Berberine and RNAi-Targeting Telomerase Reverse Transcriptase (TERT) and/or Telomerase RNA Component (TERC) Caused Oxidation in Colorectal Cancer Cell Line, HCT 116: An Integrative Approach using Molecular and Metabolomic Studies
    Samad MA, Saiman MZ, Abdul Majid N, Karsani SA, Yaacob JS
    Cell Biochem Biophys, 2024 Mar;82(1):153-173.
    PMID: 38198024 DOI: 10.1007/s12013-023-01210-8
    Colorectal cancer (CRC) is the most common cancer in both men and women and is associated with increased telomerase levels and activity. The potential downstream effects of TERT and/or TERC downregulation by berberine (a telomerase inhibitor) or RNA interference (RNAi) on various target RNAs, proteins, relative telomerase activity (RTA), relative telomere length (RTL), hydrogen peroxide concentration [H2O2], percentage of cell cycle distribution, cell size and granularity as well as cellular metabolites were explored in HCT 116 cell line. Knockdown of TERT decreased TERC. The downregulation of TERT and/or TERC caused increment of [H2O2], G0/G1 phase arrest in addition to decreased S and G2/M phases, as well as diminished cell size. RTL was later reduced as a result of TERT, TERT and/or TERC downregulation which decreased RTA. It was discovered that xanthine oxidase (XO) was significantly and positively correlated at FDR-adjusted p value 
    Matched MeSH terms: HCT116 Cells
  8. Fulltext The Antiproliferative Activity of Sclerotia of Lignosus rhinocerus (Tiger Milk Mushroom)
    Lee ML, Tan NH, Fung SY, Tan CS, Ng ST
    Evid Based Complement Alternat Med, 2012;2012:697603.
    PMID: 22454675 DOI: 10.1155/2012/697603
    Lignosus rhinocerus, the tiger milk mushroom, is one of the most important medicinal mushrooms used by the indigenous people of Southeast Asia and China. It has been used to treat breast cancer. A cold water extract (LR-CW) prepared from the sclerotia of L. rhinocerus cultivar was found to exhibit antiproliferative activity against human breast carcinoma (MCF-7) and human lung carcinoma (A549), with IC(50) of 96.7 μg/mL and 466.7 μg/mL, respectively. In comparison, LR-CW did not show significant cytotoxicity against the two corresponding human normal cells, 184B5 (human breast cell) and NL 20 (human lung cell). DNA fragmentation studies suggested that the cytotoxic action of LR-CW against cancer cells is mediated by apoptosis. Sephadex G-50 gel filtration fractionation of LR-CW yielded a high-molecular-weight and a low-molecular-weight fraction. The high-molecular-weight fraction contains mainly carbohydrate (68.7%) and small amount of protein (3.6%), whereas the low-molecular-weight fraction contains 31% carbohydrate and was devoid of protein. Only the high-molecular-weight fraction exhibited antiproliferative activity against cancer cells, with IC(50) of 70.0 μg/mL and 76.7 μg/mL, respectively. Thus, the cytotoxic action of the LR-CW is due to the high-molecular-weight fraction, either the proteins or protein-carbohydrate complex.
    Matched MeSH terms: MCF-7 Cells
  9. Fulltext Cucurbitacin L 2-O-β-Glucoside Demonstrates Apoptogenesis in Colon Adenocarcinoma Cells (HT-29): Involvement of Reactive Oxygen and Nitrogen Species Regulation
    Abdelwahab SI, Hassan LE, Abdul Majid AM, Yagi SM, Mohan S, Elhassan Taha MM, et al.
    Evid Based Complement Alternat Med, 2012;2012:490136.
    PMID: 22685485 DOI: 10.1155/2012/490136
    Emerging evidence suggests that reactive oxygen (ROS) and nitrogen (RNS) species can contribute to diverse signalling pathways of inflammatory and tumour cells. Cucurbitacins are a group of highly oxygenated triterpenes. Many plants used in folk medicine to treat cancer have been found to contain cucurbitacins displaying potentially important anti-inflammatory actions. The current study was designed to investigate the anti-ROS and -RNS effects of cucurbitacin L 2-O-β-glucoside (CLG) and the role of these signaling factors in the apoptogenic effects of CLG on human colon cancer cells (HT-29). This natural cucurbitacin was isolated purely from Citrullus lanatus var. citroides (Cucurbitaceae). The results revealed that CLG was cytotoxic to HT-29. CLG increased significantly (P < 0.05) RNA and protein levels of caspase-3 in HT-29 cells when verified using a colorimetric assay and realtime qPCR, respectively. The results showed that lipopolysaccharide/interferon-gamma (LPS/INF-γ) increased nitrous oxide (NO) production inR AW264.7macrophages, whereas N(G)-nitro-L-argininemethyl ester (L-NAME) and CLG curtailed it. This compound did not reveal any cytotoxicity on RAW264.7 macrophages and human normal liver cells (WRL-68) when tested using the MTT assay. Findings of ferric reducing antioxidant power (FRAP) and oxygen radical absorption capacity (ORAC) assays demonstrate the antioxidant properties of CLG. The apoptogenic property of CLG on HT-29 cells is thus related to inhibition of reactive nitrogen and oxygen reactive species and the triggering of caspase-3-regulated apoptosis.
    Matched MeSH terms: HT29 Cells
  10. Fulltext Iron Chelation Properties of Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Analysis on Tfr/Fth Regulations and Molecular Docking
    Md Nesran ZN, Shafie NH, Md Tohid SF, Norhaizan ME, Ismail A
    Evid Based Complement Alternat Med, 2020;2020:7958041.
    PMID: 32280356 DOI: 10.1155/2020/7958041
    In many studies, green tea epigallocatechin-3-gallate (EGCG) has already shown its therapeutic effects in colorectal cancer cells (CRC). However, its mechanism of actions in CRC is poorly elucidated. Hence, this study attempts to elucidate the mechanism of actions of green tea ECGG via iron chelation activity in CRC. In order to investigate this property, HT-29 cell lines (CRC) were treated with EGCG for 24 h, 48 h, and 72 h. From western blot analysis, EGCG had upregulated transferrin receptor (TfR) protein and downregulated Ferritin-H (FtH) protein indicating that iron chelation activity has occurred in CRC. Meanwhile, the molecular docking study demonstrated that EGCG is able to strongly interact the ferritin protein with a high binding affinity (-7.3 kcal/mol) via strong hydrogen bindings to glutamic acid 64 and lysine 71; two moderate hydrogen bindings to asparagine 74 and a hydrophobic interaction to the hydrophobic pocket of lysine 71. The strong interaction predicted between EGCG to ferritin may lead to inhibition of ferritin by EGCG, thus supporting the downregulation of FtH observed in in vitro studies. Molecular docking study of TfR to EGCG cannot be modulated based on the in vitro results. In conclusion, EGCG possesses iron chelator property in CRC and this potential could be further exploited for CRC treatment.
    Matched MeSH terms: HT29 Cells
  11. Fulltext α-Mangostin Improves Glucose Uptake and Inhibits Adipocytes Differentiation in 3T3-L1 Cells via PPARγ, GLUT4, and Leptin Expressions
    Taher M, Mohamed Amiroudine MZ, Tengku Zakaria TM, Susanti D, Ichwan SJ, Kaderi MA, et al.
    Evid Based Complement Alternat Med, 2015;2015:740238.
    PMID: 25873982 DOI: 10.1155/2015/740238
    Obesity has been often associated with the occurrence of cardiovascular diseases, type 2 diabetes, and cancer. The development of obesity is also accompanied by significant differentiation of preadipocytes into adipocytes. In this study, we investigated the activity of α-mangostin, a major xanthone component isolated from the stem bark of G. malaccensis, on glucose uptake and adipocyte differentiation of 3T3-L1 cells focusing on PPARγ, GLUT4, and leptin expressions. α-Mangostin was found to inhibit cytoplasmic lipid accumulation and adipogenic differentiation. Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells. Analyses of 2-deoxy-D-[(3)H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P < 0.05) with highest activity found at 25 μM. In addition, α-mangostin increased the amount of free fatty acids (FFA) released. The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression. Induction of glucose uptake and free fatty acid release by α-mangostin were accompanied by increasing mRNA expression of GLUT4 and leptin. These evidences propose that α-mangostin might be possible candidate for the effective management of obesity in future.
    Matched MeSH terms: 3T3-L1 Cells
  12. Fulltext The Effect of Hydrocotyle sibthorpioides Lam. Extracts on In Vitro Dengue Replication
    Husin F, Chan YY, Gan SH, Sulaiman SA, Shueb RH
    Evid Based Complement Alternat Med, 2015;2015:596109.
    PMID: 25767554 DOI: 10.1155/2015/596109
    Objective. To investigate the potential effect of Hydrocotyle sibthorpioides Lam. (H. sibthorpioides) extracts against in vitro dengue viral replication. Methods. The cytotoxicity of H. sibthorpioides was evaluated using a cell viability assay. Cells were pre- and posttreated with water and methanol extracts of H. sibthorpioides, and the viral inhibitory effect was investigated by observing the morphological changes, which were further confirmed by plaque assay. Results. The methanolic extract cytotoxicity was higher in Vero and C6/36 cells than the cytotoxicity of the water extract. Preincubation of the cells with H. sibthorpioides extract showed nonexistent to mild prophylactic effects. The posttreatment of Vero cells with H. sibthorpioides methanolic extract presented higher antidengue activities when compared with the water extract. Surprisingly, posttreatment of C6/36 cells resulted in an enhancement of viral replication. Conclusion. H. sibthorpioides had variable effects on dengue viral replication, depending on the treatment, cell lines, and solvent types. This study provides important novel insights on the phytomedicinal properties of H. sibthorpioides extracts on dengue virus.
    Matched MeSH terms: Vero Cells
  13. Fulltext Cytotoxic Activities against Breast Cancer Cells of Local Justicia gendarussa Crude Extracts
    Ayob Z, Mohd Bohari SP, Abd Samad A, Jamil S
    Evid Based Complement Alternat Med, 2014;2014:732980.
    PMID: 25574182 DOI: 10.1155/2014/732980
    Justicia gendarussa methanolic leaf extracts from five different locations in the Southern region of Peninsular Malaysia and two flavonoids, kaempferol and naringenin, were tested for cytotoxic activity. Kaempferol and naringenin were two flavonoids detected in leaf extracts using gas chromatography-flame ionization detection (GC-FID). The results indicated that highest concentrations of kaempferol and naringenin were detected in leaves extracted from Mersing with 1591.80 mg/kg and 444.35 mg/kg, respectively. Positive correlations were observed between kaempferol and naringenin concentrations in all leaf extracts analysed with the Pearson method. The effects of kaempferol and naringenin from leaf extracts were examined on breast cancer cell lines (MDA-MB-231 and MDA-MB-468) using MTT assay. Leaf extract from Mersing showed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 40 μg/mL, respectively, compared to other leaf extracts. Kaempferol possessed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 34 μg/mL, respectively. These findings suggest that the presence of kaempferol in Mersing leaf extract contributed to high cytotoxicity of both MDA-MB-231 and MDA-MB-468 cancer cell lines.
    Matched MeSH terms: MCF-7 Cells
  14. Fulltext Evaluation of Bioactive Compounds, Pharmaceutical Quality, and Anticancer Activity of Curry Leaf (Murraya koenigii L.)
    Ghasemzadeh A, Jaafar HZ, Rahmat A, Devarajan T
    Evid Based Complement Alternat Med, 2014;2014:873803.
    PMID: 24693327 DOI: 10.1155/2014/873803
    In this study, we investigated some bioactive compounds and pharmaceutical qualities of curry leaf (Murraya koenigii L.) extracts from three different locations in Malaysia. The highest TF and total phenolic (TP) contents were observed in the extracts from Kelantan (3.771 and 14.371 mg/g DW), followed by Selangor (3.146 and 12.272 mg/g DW) and Johor (2.801 and 12.02 mg/g DW), respectively. High quercetin (0.350 mg/g DW), catechin (0.325 mg/g DW), epicatechin (0.678 mg/g DW), naringin (0.203 mg/g DW), and myricetin (0.703 mg/g DW) levels were observed in the extracts from Kelantan, while the highest rutin content (0.082 mg/g DW) was detected in the leaves from Selangor. The curry leaf extract from Kelantan exhibited higher concentration of gallic acid (0.933 mg/g DW) than that from Selangor (0.904 mg/g DW) and Johor (0.813 mg/g DW). Among the studied samples, the ones from Kelantan exhibited the highest radical scavenging activity (DPPH, 66.41%) and ferric reduction activity potential (FRAP, 644.25  μ m of Fe(II)/g) followed by those from Selangor (60.237% and 598.37  μ m of Fe(II)/g) and Johor (50.76% and 563.42  μ m of Fe(II)/g), respectively. A preliminary screening showed that the curry leaf extracts from all the locations exhibited significant anticarcinogenic effects inhibiting the growth of breast cancer cell line (MDA-MB-231) and maximum inhibition of MDA-MB-231 cell was observed with the curry leaf extract from Kelantan. Based on these results, it is concluded that Malaysian curry leaf collected from the North (Kelantan) might be potential source of potent natural antioxidant and beneficial chemopreventive agents.
    Matched MeSH terms: MCF-7 Cells
  15. Fulltext Tualang honey promotes apoptotic cell death induced by tamoxifen in breast cancer cell lines
    Yaacob NS, Nengsih A, Norazmi MN
    Evid Based Complement Alternat Med, 2013;2013:989841.
    PMID: 23476711 DOI: 10.1155/2013/989841
    Tualang honey (TH) is rich in flavonoids and phenolic acids and has significant anticancer activity against breast cancer cells comparable to the effect of tamoxifen (TAM), in vitro. The current study evaluated the effects of TH when used in combination with TAM on MCF-7 and MDA-MB-231 cells. We observed that TH promoted the anticancer activity of TAM in both the estrogen receptor-(ER-)responsive and ER-nonresponsive human breast cancer cell lines. Flow cytometric analyses indicated accelerated apoptosis especially in MDA-MB-231 cells and with the involvement of caspase-3/7, -8 and -9 activation as shown by fluorescence microscopy. Depolarization of the mitochondrial membrane was also increased in both cell lines when TH was used in combination with TAM compared to TAM treatment alone. TH may therefore be a potential adjuvant to be used with TAM for reducing the dose of TAM, hence, reducing TAM-induced adverse effects.
    Matched MeSH terms: MCF-7 Cells
  16. Fulltext Hydroxyethyl cellulose functionalised with maleimide groups as a new excipient with enhanced mucoadhesive properties
    Buang F, Fu M, Chatzifragkou A, Amin MCIM, Khutoryanskiy VV
    Int J Pharm, 2023 Jul 25;642:123113.
    PMID: 37301242 DOI: 10.1016/j.ijpharm.2023.123113
    Hydroxyethylcellulose (HEC) is a non-ionic water-soluble polymer with poor mucoadhesive properties. The mucoadhesive properties of hydroxyethylcellulose can be improved by modifying it through conjugation with molecules containing maleimide groups. Maleimide groups interact with the thiol groups present in cysteine domains in the mucin via Michael addition reaction under physiological conditions to form a strong mucoadhesive bond. This will prolong the residence time of a dosage form containing this modified polymer and drug on mucosal surfaces. In this study HEC was modified by reaction with 4-bromophenyl maleimide in varying molar ratios and the successful synthesis was confirmed using 1H NMR and FTIR spectroscopies. The safety of the newly synthesised polymer derivatives was assessed with in vivo planaria assays and in vitro MTT assay utilising Caco-2 cell line. The synthesized maleimide-functionalised HEC solutions were sprayed onto blank tablets to develop a model dosage form. The physical properties and mucoadhesive behavior of these tablets were evaluated using a tensile test with sheep buccal mucosa. The maleimide-functionalised HEC exhibited superior mucoadhesive properties compared to unmodified HEC.
    Matched MeSH terms: Caco-2 Cells
  17. Fulltext Analysis of self-renewing and differentiation-related microRNAs and transcription factors in multilineage mouse hematopoietic stem/progenitor cells induced by 1,4-benzoquinone
    Dewi R, Yusoff NA, Abdul Razak SR, Abd Hamid Z
    PeerJ, 2023;11:e15608.
    PMID: 37456886 DOI: 10.7717/peerj.15608
    BACKGROUND: HSPCs are targets for benzene-induced hematotoxicity and leukemogenesis. However, benzene toxicity targeting microRNAs (miRNAs) and transcription factors (TF) that are involve in regulating self-renewing and differentiation of HSPCs comprising of different hematopoietic lineages remains poorly understood. In this study, the effect of a benzene metabolite, 1,4-benzoquinone (1,4-BQ) exposure, in HSPCs focusing on the self-renewing (miRNAs: miR-196b and miR-29a; TF: HoxB4, Bmi-1) and differentiation (miRNAs: miR-181a, TF: GATA3) pathways were investigated.

    METHODS: Freshly isolated mouse BM cells were initially exposed to 1,4-BQ at 1.25 to 5 µM for 24 h, followed by miRNAs and TF studies in BM cells. Then, the miRNAs expression was further evaluated in HSPCs of different lineages comprised of myeloid, erythroid and pre-B lymphoid progenitors following 7-14 days of colony forming unit (CFU) assay.

    RESULTS: Exposure to 1,4-BQ in BM cells significantly (p 

    Matched MeSH terms: Hematopoietic Stem Cells
  18. Case Report: Cord blood-derived natural killer cells as new potential immunotherapy drug for solid tumor: a case study for endometrial cancer
    Mu Y, Tong J, Wang Y, Yang Y, Wu X
    Front Immunol, 2023;14:1213161.
    PMID: 37457710 DOI: 10.3389/fimmu.2023.1213161
    Adoptive transfer of natural killer (NK) cells represents a viable treatment method for patients with advanced malignancies. Our team previously developed a simple, safe, and cost-effective method for obtaining high yields of pure and functional NK cells from cord blood (CB) without the need for cell sorting, feeder cells, or multiple cytokines. We present the case of a 52-year-old female patient diagnosed with poorly differentiated stage IVB (T3N2M1) endometrial cancer, who exhibited leukemoid reaction and pretreatment thrombocytosis as paraneoplastic syndromes. The patient received two courses of CB-derived NK (CB-NK) cell immunotherapy between March and September 2022, due to her extremely low NK cell activity. Two available CB units matched at 8/10 HLA with KIR-mismatch were chosen, and we were able to produce NK cells with high yield (>1.0×1010 NK cells), purity (>90%), and function (>80%) from CB without cell sorting, feeder cells, or multiple cytokines. These cells were then adoptively transferred to the patient. No adverse effects or graft-versus-host disease were observed after infusion of CB-NK cells. Our clinical experience supports the efficacy of CB-NK cell treatment in increasing NK cell activity, depleting tumor activity, improving quality of life, and reducing the size of abdominal and pelvic masses with the disappearance of multiple lymph node metastases through the regulation of systemic antitumor immunity. Remarkably, the white blood cell and platelet counts decreased to normal levels after CB-NK cell immunotherapy. This clinical work suggests that CB-NK cell immunotherapy holds promise as a therapeutic approach for endometrial cancer.
    Matched MeSH terms: Killer Cells, Natural
  19. Molecular Cloning, Expression, Sequence Characterization and Structural Insight of Bubalus bubalis Growth Hormone-Receptor
    Gul R, Hanif MU, Gul F, Rehman HM, Saleem M, Ahmad MS, et al.
    Mol Biotechnol, 2023 Jul;65(7):1062-1075.
    PMID: 36437440 DOI: 10.1007/s12033-022-00612-y
    The current study focuses on molecular cloning, expression and structural characterization of growth hormone-receptor (GHR) and its extracellular domain as growth hormone binding protein (GHBP) from the liver of Nili-Ravi buffalo (Bubalus bubalis; Bb). RNA was isolated, genes were amplified by reverse transcriptase-polymerase chain reaction and sequence was characterized. The BbGHR sequence showed three amino acid variations in the extracellular domain when compared with Indian BbGHR. For the production of full length BbGHR and BbGHBP in Escherichia coli (E. coli) BL21 (RIPL) Codon Plus, expression plasmids were constructed under the control of T7lac promoter and isopropyl β-D thiogalactopyranoside was used as an inducer. BbGHR and BbGHBP were expressed as inclusion bodies at ~ 40% and > 30% of the total E. coli proteins, respectively. The BbGHBP was solubilized and refolded by dilution method using cysteine-cystine redox potential. The recombinant BbGHBP was purified and biological activity was checked on HeLa cell lines showing increase cell proliferation in the presence of ovine GH (oGH), hence justifying the increase in the half-life of GH in the presence of BbGHBP. For the molecular interactions of oGH-BbGHBP multiple docking programs were employed to explore the subsequent interactions which showed high binding affinity and presence of large number of hydrogen bonds. Molecular Dynamics studies performed to examine the stability of proteins and exhibited stable structures along with favorable molecular interactions. This study has described the sequence characterization of BbGHR in Nili-Ravi buffaloes and hence provided the basis for the assessment of GH-GHR binding in other Bovidae species.
    Matched MeSH terms: HeLa Cells
  20. Fulltext Parvimonas micra infection enhances proliferation, wound healing, and inflammation of a colorectal cancer cell line
    Hatta MNA, Mohamad Hanif EA, Chin SF, Low TY, Neoh HM
    Biosci Rep, 2023 Jun 28;43(6).
    PMID: 37218575 DOI: 10.1042/BSR20230609
    The gut microbiota Parvimonas micra has been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared with non-CRC controls. In the present study, we investigated the tumorigenic potential of P. micra and its regulatory pathways in CRC using HT-29, a low-grade CRC intestinal epithelial cell. For every P. micra-HT-29 interaction assay, HT-29 was co-cultured anaerobically with P. micra at an MOI of 100:1 (bacteria: cells) for 2 h. We found that P. micra increased HT-29 cell proliferation by 38.45% (P=0.008), with the highest wound healing rate at 24 h post-infection (P=0.02). In addition, inflammatory marker expression (IL-5, IL-8, CCL20, and CSF2) was also significantly induced. Shotgun proteomics profiling analysis revealed that P. micra affects the protein expression of HT-29 (157 up-regulated and 214 down-regulated proteins). Up-regulation of PSMB4 protein and its neighbouring subunits revealed association of the ubiquitin-proteasome pathway (UPP) in CRC carcinogenesis; whereas down-regulation of CUL1, YWHAH, and MCM3 signified cell cycle dysregulation. Moreover, 22 clinically relevant epithelial-mesenchymal transition (EMT)-markers were expressed in HT-29 infected with P. micra. Overall, the present study elucidated exacerbated oncogenic properties of P. micra in HT-29 via aberrant cell proliferation, enhanced wound healing, inflammation, up-regulation of UPPs, and activation of EMT pathways.
    Matched MeSH terms: HT29 Cells
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