Displaying publications 81 - 100 of 1079 in total

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  1. Fulltext Proteomic Signature of Dysfunctional Circulating Endothelial Colony-Forming Cells of Young Adults
    Tan CMJ, Lewandowski AJ, Williamson W, Huckstep OJ, Yu GZ, Fischer R, et al.
    J Am Heart Assoc, 2021 Aug 03;10(15):e021119.
    PMID: 34275329 DOI: 10.1161/JAHA.121.021119
    Background A subpopulation of endothelial progenitor cells called endothelial colony-forming cells (ECFCs) may offer a platform for cellular assessment in clinical studies because of their remarkable angiogenic and expansion potentials in vitro. Despite endothelial cell function being influenced by cardiovascular risk factors, no studies have yet provided a comprehensive proteomic profile to distinguish functional (ie, more angiogenic and expansive cells) versus dysfunctional circulating ECFCs of young adults. The aim of this study was to provide a detailed proteomic comparison between functional and dysfunctional ECFCs. Methods and Results Peripheral blood ECFCs were isolated from 11 subjects (45% men, aged 27±5 years) using Ficoll density gradient centrifugation. ECFCs expressed endothelial and progenitor surface markers and displayed cobblestone-patterned morphology with clonal and angiogenic capacities in vitro. ECFCs were deemed dysfunctional if <1 closed tube formed during the in vitro tube formation assay and proliferation rate was <20%. Hierarchical functional clustering revealed distinct ECFC proteomic signatures between functional and dysfunctional ECFCs with changes in cellular mechanisms involved in exocytosis, vesicle transport, extracellular matrix organization, cell metabolism, and apoptosis. Targeted antiangiogenic proteins in dysfunctional ECFCs included SPARC (secreted protein acidic and rich in cysteine), CD36 (cluster of differentiation 36), LUM (lumican), and PTX3 (pentraxin-related protein PYX3). Conclusions Circulating ECFCs with impaired angiogenesis and expansion capacities have a distinct proteomic profile and significant phenotype changes compared with highly angiogenic endothelial cells. Impaired angiogenesis in dysfunctional ECFCs may underlie the link between endothelial dysfunction and cardiovascular disease risks in young adults.
    Matched MeSH terms: Cell Proliferation*
  2. Fulltext PIP4Ks impact on PI3K, FOXP3, and UHRF1 signaling and modulate human regulatory T cell proliferation and immunosuppressive activity
    Poli A, Abdul-Hamid S, Zaurito AE, Campagnoli F, Bevilacqua V, Sheth B, et al.
    Proc Natl Acad Sci U S A, 2021 08 03;118(31).
    PMID: 34312224 DOI: 10.1073/pnas.2010053118
    Regulatory T cells (Tregs) play fundamental roles in maintaining peripheral tolerance to prevent autoimmunity and limit legitimate immune responses, a feature hijacked in tumor microenvironments in which the recruitment of Tregs often extinguishes immune surveillance through suppression of T-effector cell signaling and tumor cell killing. The pharmacological tuning of Treg activity without impacting on T conventional (Tconv) cell activity would likely be beneficial in the treatment of various human pathologies. PIP4K2A, 2B, and 2C constitute a family of lipid kinases that phosphorylate PtdIns5P to PtdIns(4,5)P 2 They are involved in stress signaling, act as synthetic lethal targets in p53-null tumors, and in mice, the loss of PIP4K2C leads to late onset hyperinflammation. Accordingly, a human single nucleotide polymorphism (SNP) near the PIP4K2C gene is linked with susceptibility to autoimmune diseases. How PIP4Ks impact on human T cell signaling is not known. Using ex vivo human primary T cells, we found that PIP4K activity is required for Treg cell signaling and immunosuppressive activity. Genetic and pharmacological inhibition of PIP4K in Tregs reduces signaling through the PI3K, mTORC1/S6, and MAPK pathways, impairs cell proliferation, and increases activation-induced cell death while sparing Tconv. PIP4K and PI3K signaling regulate the expression of the Treg master transcriptional activator FOXP3 and the epigenetic signaling protein Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). Our studies suggest that the pharmacological inhibition of PIP4K can reprogram human Treg identity while leaving Tconv cell signaling and T-helper differentiation to largely intact potentially enhancing overall immunological activity.
    Matched MeSH terms: Cell Proliferation
  3. Protein profile of MCF-7 breast cancer cell line treated with lectin delivered by CaCO3NPs revealed changes in molecular chaperones, cytoskeleton, and membrane-associated proteins
    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 Proliferation/drug effects
  4. Fulltext Chemopreventive effects of pterostilbene through p53 and cell cycle in mouse lung of squamous cell carcinoma model
    Surien O, Ghazali AR, Masre SF
    Sci Rep, 2021 Jul 21;11(1):14862.
    PMID: 34290382 DOI: 10.1038/s41598-021-94508-7
    Cell proliferation and cell death abnormalities are strongly linked to the development of cancer, including lung cancer. The purpose of this study was to investigate the effect of pterostilbene on cell proliferation and cell death via cell cycle arrest during the transition from G1 to S phase and the p53 pathway. A total of 24 female Balb/C mice were randomly categorized into four groups (n = 6): N-nitroso-tris-chloroethyl urea (NTCU) induced SCC of the lungs, vehicle control, low dose of 10 mg/kg PS + NTCU (PS10), and high dose of 50 mg/kg PS + NTCU (PS50). At week 26, all lungs were harvested for immunohistochemistry and Western blotting analysis. Ki-67 expression is significantly lower, while caspase-3 expression is significantly higher in PS10 and PS50 as compared to the NTCU (p cell cycle arrest.
    Matched MeSH terms: Cell Proliferation/genetics
  5. Fulltext Dynamic behavior and stabilization of brain cell reconstitution after stroke under the proliferation and differentiation processes for stem cells
    Alqarni AJ, Rambely AS, Alharbi SA, Hashim I
    Math Biosci Eng, 2021 07 19;18(5):6288-6304.
    PMID: 34517534 DOI: 10.3934/mbe.2021314
    Stem cells play a critical role in regulatory operations, overseeing tissue regeneration and tissue homeostasis. In this paper, a mathematical model is proposed and analyzed to study the impact of stem cell transplantation on the dynamical behavior of stroke therapy, which is assumed to be based on transplanting dead brain cells following a stroke. We transform the method of using hierarchical cell systems into a method of using different compartment variables by using ordinary differential equations, each of which elucidates a well-defined differentiation stage along with the effect of mature cells in improving the brain function after a stroke. Stem cells, progenitor cells, and the impacts of the stem cells transplanted on brain cells are among the variables considered. The model is studied analytically and solved numerically using the fourth-order Runge-Kutta method. We analyze the structure of equilibria, the ability of neural stem cells to proliferate and differentiate, and the stability properties of equilibria for stem cell transplantation. The model is considered to be stable after transplantation if the stem cells and progenitor cells differentiate into mature nerve cells in the brain. The results of the model analysis and simulation facilitate the identification of various biologically probable parameter sets that can explain the optimal time for stem cell replacement of damaged brain cells. Associating the classified parameter sets with recent experimental and clinical findings contributes to a better understanding of therapeutic mechanisms that promote the reconstitution of brain cells after an ischemic stroke.
    Matched MeSH terms: Cell Proliferation
  6. Fulltext Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells
    Wan Mohd Tajuddin WNB, Abas F, Othman I, Naidu R
    Int J Mol Sci, 2021 Jul 10;22(14).
    PMID: 34299042 DOI: 10.3390/ijms22147424
    Diarylpentanoid (DAP), an analog that was structurally modified from a naturally occurring curcumin, has shown to enhance anticancer efficacy compared to its parent compound in various cancers. This study aims to determine the cytotoxicity, antiproliferative, and apoptotic activity of diarylpentanoid MS13 on two subtypes of non-small cell lung cancer (NSCLC) cells: squamous cell carcinoma (NCI-H520) and adenocarcinoma (NCI-H23). Gene expression analysis was performed using Nanostring PanCancer Pathways Panel to determine significant signaling pathways and targeted genes in these treated cells. Cytotoxicity screening revealed that MS13 exhibited greater inhibitory effect in NCI-H520 and NCI-H23 cells compared to curcumin. MS13 induced anti-proliferative activity in both cells in a dose- and time-dependent manner. Morphological analysis revealed that a significant number of MS13-treated cells exhibited apoptosis. A significant increase in caspase-3 activity and decrease in Bcl-2 protein concentration was noted in both MS13-treated cells in a time- and dose-dependent manner. A total of 77 and 47 differential expressed genes (DEGs) were regulated in MS13 treated-NCI-H520 and NCI-H23 cells, respectively. Among the DEGs, 22 were mutually expressed in both NCI-H520 and NCI-H23 cells in response to MS13 treatment. The top DEGs modulated by MS13 in NCI-H520-DUSP4, CDKN1A, GADD45G, NGFR, and EPHA2-and NCI-H23 cells-HGF, MET, COL5A2, MCM7, and GNG4-were highly associated with PI3K, cell cycle-apoptosis, and MAPK signaling pathways. In conclusion, MS13 may induce antiproliferation and apoptosis activity in squamous cell carcinoma and adenocarcinoma of NSCLC cells by modulating DEGs associated with PI3K-AKT, cell cycle-apoptosis, and MAPK pathways. Therefore, our present findings could provide an insight into the anticancer activity of MS13 and merits further investigation as a potential anticancer agent for NSCLC cancer therapy.
    Matched MeSH terms: Cell Proliferation/drug effects
  7. Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro
    Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.
    Life Sci, 2021 Jul 01;276:119436.
    PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436
    Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
    Matched MeSH terms: Cell Proliferation*
  8. Mutated Shiitake extracts inhibit melanin-producing neural crest-derived cells in zebrafish embryo
    Mahmood I, Azfaralariff A, Mohamad A, Airianah OB, Law D, Dyari HRE, et al.
    Comp Biochem Physiol C Toxicol Pharmacol, 2021 Jul;245:109033.
    PMID: 33737223 DOI: 10.1016/j.cbpc.2021.109033
    The ability of natural extracts to inhibit melanocyte activity is of great interest to researchers. This study evaluates and explores the ability of mutated Shiitake (A37) and wildtype Shiitake (WE) extract to inhibit this activity. Several properties such as total phenolic (TPC) and total flavonoid content (TFC), antioxidant activity, effect on cell and component profiling were conducted. While having no significant differences in total phenolic content, mutation resulted in A37 having a TFC content (1.04 ± 0.7 mg/100 ml) compared to WE (0.86 ± 0.9 mg/100 ml). Despite that, A37 extract has lower antioxidant activity (EC50, A37 = 549.6 ± 2.70 μg/ml) than WE (EC50 = 52.8 ± 1.19 μg/ml). Toxicity tests on zebrafish embryos show that both extracts, stop the embryogenesis process when the concentration used exceeds 900 μg/ml. Although both extracts showed pigmentation reduction in zebrafish embryos, A37 extract showed no effect on embryo heartbeat. Cell cycle studies revealed that WE significantly affect the cell cycle while A37 not. Further tests found that these extracts inhibit the phosphorylation of Glycogen synthase kinase 3 β (pGSK3β) in HS27 cell line, which may explain the activation of apoptosis in melanin-producing cells. It was found that from 19 known compounds, 14 compounds were present in both WE and A37 extracts. Interestingly, the presence of decitabine in A37 extract makes it very potential for use in the medical application such as treatment of melanoma, skin therapy and even cancer.
    Matched MeSH terms: Cell Proliferation/drug effects
  9. Anticancer activities of dietary benzyl isothiocyanate: A comprehensive review
    Dinh TN, Parat MO, Ong YS, Khaw KY
    Pharmacol Res, 2021 07;169:105666.
    PMID: 33989764 DOI: 10.1016/j.phrs.2021.105666
    Benzyl isothiocyanate (BITC) is one of the common isothiocyanates found in cruciferous vegetables such as broccoli, cabbage or watercress. Preclinical studies report of its effectiveness in the prevention and treatment against several cancers. This review aims to report and discuss findings on anticancer activities of BITC and its modes of action against 14 types of cancer. A literature search was conducted using the keywords "BITC" and "anticancer" from PubMed, Google Scholar and CINAHL Plus to obtain relevant research articles. This review highlights the anticancer efficacy of BITC through modulation of various signaling pathways involved in apoptosis, cell proliferation, cell cycle arrest, metastasis, angiogenesis, autophagy and the effects of BITC in combination with other drugs. With the available pharmacology evidence, we conclude that further studies are needed to validate its effectiveness in humans for further development and translation into prophylaxis or therapy by promoting optimal therapeutic effects and minimizing toxicity in cancer treatment.
    Matched MeSH terms: Cell Proliferation/drug effects
  10. Cimigenoside functions as a novel γ-secretase inhibitor and inhibits the proliferation or metastasis of human breast cancer cells by γ-secretase/Notch axis
    Jia H, Liu M, Wang X, Jiang Q, Wang S, Santhanam RK, et al.
    Pharmacol Res, 2021 Jul;169:105686.
    PMID: 34022397 DOI: 10.1016/j.phrs.2021.105686
    Breast cancer (BC) occurrence and development tremendously affect female health. Currently breast cancer targeted drugs are still scarce. Natural products have become the main source of targeted drug for breast cancer due to low toxicity and high efficiency. Cimigenoside, natural compound isolated and purified from Cimicifuga dahurica (Turcz.) Maxim has been suggested to utilize for breast cancer treatment, however the mechanism of action has not been elucidated yet. In this article, the antitumor potential of Cimigenoside against breast cancer in vitro and in vivo study. Moreover, we further predicted the possible binding mode of Cimigenoside with γ-secretase through molecular docking studies. The results show that Cimigenoside has a significant inhibitory effect towards the proliferation or metastasis of breast cancer cells via suppressing the Notch signaling pathway-mediated mitochondrial apoptosis and EMT (epithelial mesenchymal transition). In terms of mechanism, Cimigenoside could inhibit the activation of PSEN-1, the catalytic subunit of γ-secretase, and also by cleaving the Notch protein mediated by PSEN-1. Overall, our findings provide scientific support to utilize Cimigenoside as an effective targeted drug for clinical treatment of BC.
    Matched MeSH terms: Cell Proliferation/drug effects*
  11. Vitamin D3-loaded electrospun cellulose acetate/polycaprolactone nanofibers: Characterization, in-vitro drug release and cytotoxicity studies
    Wsoo MA, Razak SIA, Bohari SPM, Shahir S, Salihu R, Kadir MRA, et al.
    Int J Biol Macromol, 2021 Jun 30;181:82-98.
    PMID: 33771547 DOI: 10.1016/j.ijbiomac.2021.03.108
    Vitamin D deficiency is now a global health problem; despite several drug delivery systems for carrying vitamin D due to low bioavailability and loss bioactivity. Developing a new drug delivery system to deliver vitamin D3 is a strong incentive in the current study. Hence, an implantable drug delivery system (IDDS) was developed from the electrospun cellulose acetate (CA) and ε-polycaprolactone (PCL) nanofibrous membrane, in which the core of implants consists of vitamin D3-loaded CA nanofiber (CAVD) and enclosed in a thin layer of the PCL membrane (CAVD/PCL). CA nanofibrous mat loaded with vitamin D3 at the concentrations of 6, 12, and 20% (w/w) of vitamin D3 were produced using electrospinning. The smooth and bead-free fibers with diameters ranged from 324 to 428 nm were obtained. The fiber diameters increased with an increase in vitamin D3 content. The controlled drug release profile was observed over 30-days, which fit with the zero-order model (R2 > 0.96) in the first stage. The mechanical properties of IDDS were improved. Young's modulus and tensile strength of CAVD/PCL (dry) were161 ± 14 and 13.07 ± 2.5 MPa, respectively. CA and PCL nanofibers are non-cytotoxic based on the results of the in-vitro cytotoxicity studies. This study can further broaden in-vivo study and provide a reference for developing a new IDDS to carry vitamin D3 in the future.
    Matched MeSH terms: Cell Proliferation/drug effects
  12. Restitution of epithelial cells during intestinal mucosal wound healing: The effect of a polysaccharide from the sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden
    Veeraperumal S, Qiu HM, Tan CS, Ng ST, Zhang W, Tang S, et al.
    J Ethnopharmacol, 2021 Jun 28;274:114024.
    PMID: 33727110 DOI: 10.1016/j.jep.2021.114024
    ETHNOPHARMACOLOGICAL RELEVANCE: Lignosus rhinocerotis (Cooke) Ryvarden cultivar TM02, also known as tiger's milk mushroom, is regarded as important folk medicine in Malaysia, while is used for the treatment of liver cancer, chronic hepatitis, gastric ulcer in traditional Chinese medicine. However, there is no compilation of scientific evidence that its protection for gastric, and no attempts have been made to understand how polysaccharides in Lignosus rhinocerotis might promote intestinal mucosal wound healing.

    AIM OF THE STUDY: This study aimed to investigate the effect and mechanism of β-glucan prepared from L. rhinocerotis using an enzymatic method on epithelial restitution during intestinal mucosal damage.

    MATERIALS AND METHODS: Based on FT-IR, MALDI-TOF-MS, HPSEC-MALLS-RID, and AFM, the structure of polysaccharides from L. rhinocerotis was analysed. In addition, polysaccharides were used to test for wound healing activity in IEC-6 cells by measuring cell migration, proliferation, and expression of cell division control protein 42, Rac-1, RhoA, and Par-3.

    RESULTS: β-glucan was extracted using enzyme-assisted extraction, and a yield of approximately 8.5 ± 0.8% was obtained from the dried biomass. The β-glucan extracted by enzyme-assisted extraction (EAE) of polysaccharides was composed entirely of D-glucose with a total carbohydrate content of 95.5 ± 3.2%. The results of HPLC, FTIR, and MALDI-TOF-MS analyses revealed EAEP to be confirmed as β-glucan. The molecular weight of prepared β-glucan was found to be 5.315 × 104 g/mol by HPSEC-MALLS-RID. Furthermore, mucosal wound healing studies showed that the treatment of IEC-6 with a β-glucan concentration of 200 μg/mL promoted cell migration and proliferation, and it enhanced the protein expression of cell division control protein 42, Rac-1, RhoA, and Par-3.

    CONCLUSIONS: The present study reveals that the prepared β-glucan accelerates intestinal epithelial cell proliferation and migration via activation of Rho-dependent pathway. Hence, β-glucan can be employed as a prospective therapeutic agent for the treatment of diseases associated with gastrointestinal mucosal damage, such as peptic ulcers and inflammatory bowel disease.

    Matched MeSH terms: Cell Proliferation/drug effects
  13. Fulltext Mechanistic Actions between Garcinia atroviridis Essential Oil and 2 Deoxy-d-glucose in Cultured PANC-1 Human Pancreatic Cancer Cells
    Nik Mohamed Kamal NNS, Abdul Aziz FA, Tan WN, Fauzi AN, Lim V
    Molecules, 2021 Jun 09;26(12).
    PMID: 34207699 DOI: 10.3390/molecules26123518
    Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.
    Matched MeSH terms: Cell Proliferation/drug effects
  14. Diabetic cataract in the Nile grass rat: A longitudinal phenotypic study of pathology formation
    Ranaei Pirmardan E, Barakat A, Zhang Y, Naseri M, Hafezi-Moghadam A
    FASEB J, 2021 Jun;35(6):e21593.
    PMID: 33991133 DOI: 10.1096/fj.202100353R
    Diabetes is a major risk factor for cataract, the leading cause of blindness worldwide. There is an unmet need for a realistic model of diabetic cataract for mechanistic and longitudinal studies, as existing models do not reflect key aspects of the complex human disease. Here, we introduce and characterize diabetic cataract in the Nile grass rat (NGR, Arvicanthis niloticus), an established model of metabolic syndrome and type 2 diabetes (T2D). We conducted a longitudinal study of cataract in over 88 NGRs in their non-diabetic, pre-diabetic, and diabetic stages of metabolism. Oral glucose tolerance test (OGTT) results distinguished the metabolic stages. Diverse cataract types were observed in the course of diabetes, including cortical, posterior subcapsular (PSC), and anterior subcapsular (ASC), all of which succeeded a characteristic dotted ring stage in all animals. The onset ages of diabetes and cataract were 44 ± 3 vs 29 ± 1 (P cells (LECs) in non-diabetic young NGRs expressed the stress marker GRP78, as did LECs and migrated cells in the lenses of diabetic animals. Elucidating mechanisms underlying LEC proliferation and migration will be clinically valuable in prevention and treatment of posterior capsule opacification, a dreaded complication of cataract surgery. Marked changes in N-cadherin expression emphasized a role for LEC integrity in cataractogenesis. Apoptotic cells were dispersed in the equatorial areas in early cataractogenesis. Our study reveals diverse cataract types that spontaneously develop in the diabetic NGR, and which uniquely mirror the cataract and its chronic course of development in individuals with diabetes. We provide mechanistic insights into early stages of diabetic cataract. These unique characteristics make NGR highly suited for mechanistic studies, especially in the context of metabolism, diabetes, and aging.
    Matched MeSH terms: Cell Proliferation
  15. Fulltext Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3'-Untranslated Region of DLC1
    Ankasha SJ, Shafiee MN, Abdul Wahab N, Raja Ali RA, Mokhtar NM
    Int J Environ Res Public Health, 2021 05 27;18(11).
    PMID: 34071861 DOI: 10.3390/ijerph18115741
    High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer with highly metastatic properties. A small non-coding RNA, microRNA (miRNA) was discovered to be a major regulator in many types of cancers through binding at the 3'-untranslated region (3'UTR), leading to degradation of the mRNA. In this study, we sought to investigate the underlying mechanisms involved in the dysregulation of miR-200c-3p in HGSC progression and metastasis. We identified the upregulation of miR-200c-3p expression in different stages of HGSC clinical samples and the downregulation of the tumor suppressor gene, Deleted in Liver Cancer 1 (DLC1), expression. Over expression of miR-200c-3p in HGSC cell lines downregulated DLC1 but upregulated the epithelial marker, E-cadherin (CDH1). Based on in silico analysis, two putative binding sites were found within the 3'UTR of DLC1, and we confirmed the direct binding of miR-200c-3p to the target binding motif at position 1488-1495 bp of 3'UTR of DLC1 by luciferase reporter assay in a SKOV3 cell line co-transfected with vectors and miR-200c-3p mimic. These data showed that miR-200c-3p regulated the progression of HGSC by regulating DLC1 expression post-transcription and can be considered as a promising target for therapeutic purposes.
    Matched MeSH terms: Cell Proliferation
  16. Fulltext Synthesis and characterizations iron oxide carbon nanotubes nanocomposite by laser ablation for anti-microbial applications
    Al-Salih M, Samsudin S, Arshad SS
    J Genet Eng Biotechnol, 2021 May 18;19(1):76.
    PMID: 34003402 DOI: 10.1186/s43141-021-00161-y
    BACKGROUND: Environmental contamination by microbes is a major public health concern. A damp environment is one of the potential sources for microbe proliferation. Smart synthesis nanocatalytic coatings on surfaces, food, and material from different pathogen bacteria can inhibit using the Fe3O4/CNTs as anti-microbial growth can effectively curb this growing threat. In this present work, the anti-microbial efficacy of synthesis of a compound nanoparticle-containing iron oxide-multi-walled carbon nanotube was combined by laser ablation PLAL and explored the anti-bacterial action of colloidal solution of Fe3O4/CNTs NPs that was evaluated against bacteria which is classified as gram-negative (Escherichia coli (E. coli), Klebsiella pneumonia (K. pneumonia), and also that is identified as gram-positive (Streptococcus pyogenes (S .pyogenes) and Staphylococcus aureus (S. aureus) under visible light irradiation.

    RESULTS: Doping of a minute fraction of iron(III) salt (0.5 mol%) in a volatile solvent (ethanol) was carried out via the sol-gel technique. Fe3O4 was further calcined at various temperatures (in the range of 500-700 °C) to evaluate the thermal stability of the Fe3O4 nanoporous oxidizer nanoparticles. The physicochemical properties of the samples were characterized through X-ray diffraction (XRD), atomic force microscopy (AFM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and UV-Visible spectroscopy techniques. XRD results revealed that the nanoparticles framework of Fe3O4 was maintained well up to 650 °C by the Fe dopant. UV-Vis results suggested that absorption property of combination Fe3O4/CNTs nanopowder by PLAL was enhanced and the band gap is reduced into 2.0 eV.

    CONCLUSIONS: Density functional theory (DFT) studies emphasize the introduction of Fe+ and Fe2+ ions by replacing other ions in the CNT lattice, therefore creating oxygen vacancies. These further promoted anti-microbial efficiency. A significantly high bacterial inactivation that indicates results was evaluated and that the mean estimations of restraint were determined from triple assessment in every appraisal at 400 ml which represent the best anti-bacterial action against gram-positive and gram-negative microbes.

    Matched MeSH terms: Cell Proliferation
  17. Fulltext Application of Computational Method in Designing a Unit Cell of Bone Tissue Engineering Scaffold: A Review
    Mustafa NS, Akhmal NH, Izman S, Ab Talib MH, Shaiful AIM, Omar MNB, et al.
    Polymers (Basel), 2021 May 14;13(10).
    PMID: 34069101 DOI: 10.3390/polym13101584
    The design of a scaffold of bone tissue engineering plays an important role in ensuring cell viability and cell growth. Therefore, it is a necessity to produce an ideal scaffold by predicting and simulating the properties of the scaffold. Hence, the computational method should be adopted since it has a huge potential to be used in the implementation of the scaffold of bone tissue engineering. To explore the field of computational method in the area of bone tissue engineering, this paper provides an overview of the usage of a computational method in designing a unit cell of bone tissue engineering scaffold. In order to design a unit cell of the scaffold, we discussed two categories of unit cells that can be used to design a feasible scaffold, which are non-parametric and parametric designs. These designs were later described and being categorised into multiple types according to their characteristics, such as circular structures and Triply Periodic Minimal Surface (TPMS) structures. The advantages and disadvantages of these designs were discussed. Moreover, this paper also represents some software that was used in simulating and designing the bone tissue scaffold. The challenges and future work recommendations had also been included in this paper.
    Matched MeSH terms: Cell Proliferation
  18. Fulltext Hyperthermia by near infrared radiation induced immune cells activation and infiltration in breast tumor
    Wan Mohd Zawawi WFA, Hibma MH, Salim MI, Jemon K
    Sci Rep, 2021 05 13;11(1):10278.
    PMID: 33986437 DOI: 10.1038/s41598-021-89740-0
    Breast cancer is the most common cancer that causes death in women. Conventional therapies, including surgery and chemotherapy, have different therapeutic effects and are commonly associated with risks and side effects. Near infrared radiation is a technique with few side effects that is used for local hyperthermia, typically as an adjuvant to other cancer therapies. The understanding of the use of near NIR as a monotherapy, and its effects on the immune cells activation and infiltration, are limited. In this study, we investigate the effects of HT treatment using NIR on tumor regression and on the immune cells and molecules in breast tumors. Results from this study demonstrated that local HT by NIR at 43 °C reduced tumor progression and significantly increased the median survival of tumor-bearing mice. Immunohistochemical analysis revealed a significant reduction in cells proliferation in treated tumor, which was accompanied by an abundance of heat shock protein 70 (Hsp70). Increased numbers of activated dendritic cells were observed in the draining lymph nodes of the mice, along with infiltration of T cells, NK cells and B cells into the tumor. In contrast, tumor-infiltrated regulatory T cells were largely diminished from the tumor. In addition, higher IFN-γ and IL-2 secretion was observed in tumor of treated mice. Overall, results from this present study extends the understanding of using local HT by NIR to stimulate a favourable immune response against breast cancer.
    Matched MeSH terms: Cell Proliferation/radiation effects
  19. Fulltext Synthesis and Anti-Pancreatic Cancer Activity Studies of Novel 3-Amino-2-hydroxybenzofused 2-Phospha-γ-lactones
    Balam SK, Soora Harinath J, Krishnammagari SK, Gajjala RR, Polireddy K, Baki VB, et al.
    ACS Omega, 2021 May 04;6(17):11375-11388.
    PMID: 34056293 DOI: 10.1021/acsomega.1c00360
    A series of 3-amino-2-hydroxybenzofused 2-phosphalactones (4a-l) has been synthesized from the Kabachnik-Fields reaction via a facile route from a one-pot three-component reaction of diphenylphosphite with various 2-hydroxybenzaldehyes and heterocyclic amines in a new way of expansion. The in vitro anti-cell proliferation studies by MTT assay have revealed them as potential Panc-1, Miapaca-2, and BxPC-3 pancreatic cell growth inhibitors, and the same is supported by molecular docking, QSAR, and ADMET studies. The MTT assay of their SAHA derivatives against the same cell lines evidenced them as potential HDAC inhibitors and identified 4a, 4b, and 4k substituted with 1,3-thiazol, 1,3,4-thiadiazol, and 5-sulfanyl-1,3,4-thiadiazol moieties on phenyl and diethylamino phenyl rings as potential ones. Additionally, the flow cytometric analyses of 4a, 4b, and 4k against BxPC-3 cells revealed compound 4k as a lead compound that arrests the S phase cell cycle growth at low micromolar concentrations. The ADMET properties have ascertained their inherent pharmacokinetic potentiality, and the wholesome results prompted us to report it as the first study on anti-pancreatic cancer activity of cyclic α-aminophosphonates. Ultimately, this study serves as a good contribution to update the existing knowledge on the anticancer organophosphorus heterocyclic compounds and elevates the scope for generation of new anticancer drugs. Further, the studies like QSAR, drug properties, toxicity risks, and bioactivity scores predicted for them have ascertained the synthesized compounds as newer and potential drug candidates. Hence, this study had augmented the array of α-aminophosphonates by adding a new collection of 3-amino-2-hydroxybenzofused 2-phosphalactones, a class of cyclic α-aminophosphonates, to it, which proved them as potential anti-pancreatic cancer agents.
    Matched MeSH terms: Cell Proliferation
  20. Fulltext Flavokawain C exhibits anti-tumor effects on in vivo HCT 116 xenograft and identification of its apoptosis-linked serum biomarkers via proteomic analysis
    Phang CW, Abd Malek SN, Karsani SA
    Biomed Pharmacother, 2021 May;137:110846.
    PMID: 33761587 DOI: 10.1016/j.biopha.2020.110846
    Chalcones and their derivatives belong to the flavonoid family. They have been extensively studied for their anticancer properties and some have been approved for clinical use. In this study, the in vivo anti-tumor activity of flavokawain C (FKC), a naturally occurring chalcone found in Kava (Piper methysticum Forst) was evaluated in HCT 116 cells (colon carcinoma). We also attempted to identify potential biomarkers and/or molecular targets in serum with applicability in predicting treatment outcome. The anti-tumor effects and toxicity of FKC were assessed using the xenograft nude mice model. Cisplatin was used as positive control. The anti-proliferative and apoptotic activities were then evaluated in tumor tissues treated with FKC. Furthermore, two-dimensional electrophoresis (2-DE) followed by protein identification using MALDI-TOF/TOF-MS/MS was performed to compare the serum proteome profiles between healthy nude mice and nude mice bearing HCT 116 tumor treated with vehicle solution and FKC, respectively. Our results showed that FKC treatment significantly inhibited HCT 116 tumor growth. In vivo toxicity studies showed that administration of FKC did not cause damage to major organs and had no significant effect on body weight. FKC was found to induce apoptosis in tumor, and this was associated with increased expression of cleaved caspase-3 and decreased expression of Ki67 in tumor tissues. Our proteomic analysis identified five proteins that changed in abundance - Ig mu chain C region (secreted form), GRP78, hemopexin, kininogen-1 and apolipoprotein E. Overall, our findings demonstrated the potential of FKC as an anti-cancer agent for the treatment of colon carcinoma.
    Matched MeSH terms: Cell Proliferation/drug effects
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