Displaying publications 221 - 240 of 348 in total

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  1. Fulltext Increased fucoxanthin in Chaetoceros calcitrans extract exacerbates apoptosis in liver cancer cells via multiple targeted cellular pathways
    Foo SC, Yusoff FM, Imam MU, Foo JB, Ismail N, Azmi NH, et al.
    Biotechnol Rep (Amst), 2019 Mar;21:e00296.
    PMID: 30581767 DOI: 10.1016/j.btre.2018.e00296
    In this study, anti-proliferative effects of C. calcitrans extract and its fucoxanthin rich fraction (FxRF) were assessed on human liver HepG2 cancer cell line. Efficacy from each extract was determined by cytotoxicity assay, morphological observation, and cell cycle analysis. Mechanisms of action observed were evaluated using multiplex gene expression analysis. Results showed that CME and FxRF induced cytotoxicity to HepG2 cells in a dose and time-dependent manner. FxRF (IC50: 18.89 μg.mL-1) was found to be significantly more potent than CME (IC50: 87.5 μg.mL-1) (p 
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2
  2. Fulltext Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus-A Review of Potential Contributing Mechanisms
    John CM, Mohamed Yusof NIS, Abdul Aziz SH, Mohd Fauzi F
    Int J Mol Sci, 2018 Dec 05;19(12).
    PMID: 30563117 DOI: 10.3390/ijms19123894
    Gestational diabetes mellitus (GDM) carries many risks, where high blood pressure, preeclampsia and future type II diabetes are widely acknowledged, but less focus has been placed on its effect on cognitive function. Although the multifactorial pathogenesis of maternal cognitive impairment is not completely understood, it shares several features with type 2 diabetes mellitus (T2DM). In this review, we discuss some key pathophysiologies of GDM that may lead to cognitive impairment, specifically hyperglycemia, insulin resistance, oxidative stress, and neuroinflammation. We explain how these incidents: (i) impair the insulin-signaling pathway and/or (ii) lead to cognitive impairment through hyperphosphorylation of τ protein, overexpression of amyloid-β and/or activation of microglia. The aforementioned pathologies impair the insulin-signaling pathway primarily through serine phosphorylation of insulin receptor substances (IRS). This then leads to the inactivation of the phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling cascade, which is responsible for maintaining brain homeostasis and normal cognitive functioning. PI3K/AKT is crucial in maintaining normal cognitive function through the inactivation of glycogen synthase kinase 3β (GSκ3β), which hyperphosphorylates τ protein and releases pro-inflammatory cytokines that are neurotoxic. Several biomarkers were also highlighted as potential biomarkers of GDM-related cognitive impairment such as AGEs, serine-phosphorylated IRS-1 and inflammatory markers such as tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), leptin, interleukin 1β (IL-1β), and IL-6. Although GDM is a transient disease, its complications may be long-term, and hence increased mechanistic knowledge of the molecular changes contributing to cognitive impairment may provide important clues for interventional strategies.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  3. Fulltext Strontium Sulfite: A New pH-Responsive Inorganic Nanocarrier to Deliver Therapeutic siRNAs to Cancer Cells
    Karim ME, Shetty J, Islam RA, Kaiser A, Bakhtiar A, Chowdhury EH
    Pharmaceutics, 2019 Feb 20;11(2).
    PMID: 30791612 DOI: 10.3390/pharmaceutics11020089
    Inorganic nanoparticles hold great potential in the area of precision medicine, particularly for treating cancer owing to their unique physicochemical properties, biocompatibility and improved pharmacokinetics properties compared to their organic counterparts. Here we introduce strontium sulfite nanoparticles as new pH-responsive inorganic nanocarriers for efficient transport of siRNAs into breast cancer cells. We employed the simplest nanoprecipitation method to generate the strontium sulfite nanoparticles (SSNs) and demonstrated the dramatic roles of NaCl and d-glucose in particle growth stabilization in order to produce even smaller nanosize particles (Na-Glc-SSN) with high affinity towards negatively charged siRNA, enabling it to efficiently enter the cancer cells. Moreover, the nanoparticles were found to be degraded with a small drop in pH, suggesting their potential capability to undergo rapid dissolution at endosomal pH so as to release the payload. While these particles were found to be nontoxic to the cells, they showed higher potency in facilitating cancer cell death through intracellular delivery and release of oncogene-specific siRNAs targeting ros1 and egfr1 mRNA transcripts, than the strontium sulfite particles prepared in absence of NaCl and d-glucose, as confirmed by growth inhibition assay. The mouse plasma binding analysis by Q-TOF LC-MS/MS demonstrated less protein binding to smaller particles of Na-Glc-SSNs. The biodistribution studies of the particles after 4 h of treatment showed Na-Glc-SSNs had less off-target distribution than SSNs, and after 24 h, all siRNAs were cleared from all major organs except the tumors. ROS1 siRNA with its potential therapeutic role in treating 4T1-induced breast tumor was selected for subsequent in vivo tumor regression study, revealing that ROS1 siRNA-loaded SSNs exerted more significant anti-tumor effects than Na-Glc-SSNs carrying the same siRNA following intravenous administration, without any systemic toxicity. Thus, strontium sulfite emerged as a powerful siRNA delivery tool with potential applications in cancer gene therapy.
    Matched MeSH terms: Proto-Oncogene Proteins
  4. Fulltext Tocotrienols and oxidative stress in ocytes and developing embryos
    Yuhaniza Shafinie Kamsani, Mohd Hamim Rajikin
    Journal of Clinical and Health Sciences, 2017;2:8-18.
    This review summarizes the impact of tocotrienols (TCTs) as antioxidants in minimizing
    oxidative stress (OS), particularly in embryos exposed to OS causing agents. OS level is
    increased, for example, by nicotine, a major alkaloid content in cigarette, which is also a source
    of exogenous reactive oxygen species (ROS). Increased nicotine-induced OS increases cell
    stress response, which is a common trigger leading to embryonic cell death. Having more
    profound anti-oxidative stress effects than its counterpart tocopherol, TCTs improve blastocyst
    implantation, foetal growth, pregnancy outcome and survival of the neonates affected by
    nicotine. In reversing cell developmental arrest caused by nicotine-induced OS, TCTs enhances
    PDK-1 expression in the P13K/Akt pathway and permit embryonic development beyond the 4-
    cell stage with the production of more morulae. At the cytoskeletal level, TCTs increase the
    number of nicotine-induced apoptotic cells, through caspase 8 activation in the mitochondria.
    TCTs facilitate rough endoplasmic reticulum (rER) stress-mediated apoptosis and autophagy,
    resulting from nicotine-induced OS. Reduced vesicular population in TCT supplemented
    oocytes on the other hand may suggest reduced secretion of apoptotic cell bodies thus probably
    minimizing vesicular apoptosis during oocyte maturation. Further extensive research is
    required to develop TCTs as a tool in specific therapeutic approaches to overcome the
    detrimental effects of OS.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  5. Fulltext Cytotoxicity, regulation of apoptotic and anti-apoptotic gene expression by IL-27 in MCF-7 and MDA-MB-231 breast cancer cell lines
    Yap Wei Boon, Shaktypreya Nadarajah, Nadiah Shidik, Noorjahan Banu Mohammed Alitheen
    Jurnal Sains Kesihatan Malaysia, 2018;16(101):15-22.
    MyJurnal
    Breast cancer is one of the commonest cancers among women. Conventional therapies cause adverse side effects in patients. Cytokine immunotherapy such as interleukin-27 (IL-27) has been sought as an alternative cancer treatment in recent years. IL-27 has been shown to improve anticancer immunity and anti-angiogenesis in cancers, however, its effect on apoptotic and anti-apoptotic gene expression especially in breast cancers is yet to be explored. Cytotoxicity of IL-27 in non-cancerous (184b5) and cancerous (MCF-7 and MDA-MB-231) breast cell lines was first determined for 24-72 h in this study. The results indicated that IL-27 treatment did not retard 184b5 cell growth, however, did inhibit MCF-7 (48 h) and MDA-MB-231 (72 h) cell growth with IC50 at 442 and 457 ng/ml, respectively. Apoptotic (TRAIL, FADD, FAS, caspase-3 and caspase-8) and anti-apoptotic (BCL-2, AKT, and COX-2) genes were then amplified from untreated (control) and treated breast cancer cells and studied. TRAIL, caspase-3, caspase-8 gene expression was significantly (p < 0.05) upregulated in treated MCF-7 (442 ng/ml) and MDA-MB-231 (457 ng/ml) cells. Expression of FADD and FAS genes was not detected in both control and treated MCF-7 and MDA-MB-231 cells. COX-2 gene was also not expressed by MCF-7 cells, but reduced significantly (p < 0.05) in treated MDA-MB-231 cells. In MDA-MB-231 cells, IL-27 treatment seemed to slightly enhance the expression of AKT and BCL-2 genes which, on the other hand, was downregulated in treated MCF-7 cells. Conclusively, IL-27 is able to inhibit breast cancer cell growth and regulate apoptotic and anti-apoptotic gene expression in breast cancer cells.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  6. Fulltext Crosstalk Between Signaling Pathways Involved in the Regulation of Airway Smooth Muscle Cell Hyperplasia
    Yap HM, Israf DA, Harith HH, Tham CL, Sulaiman MR
    Front Pharmacol, 2019;10:1148.
    PMID: 31649532 DOI: 10.3389/fphar.2019.01148
    Increased ASM mass, primarily due to ASM hyperplasia, has been recognized as a hallmark of airway remodeling in asthma. Increased ASM mass is the major contributor to the airway narrowing, thus worsening the bronchoconstriction in response to stimuli. Inflammatory mediators and growth factors released during inflammation induce increased ASM mass surrounding airway wall via increased ASM proliferation, diminished ASM apoptosis and increased ASM migration. Several major pathways, such as MAPKs, PI3K/AKT, JAK2/STAT3 and Rho kinase, have been reported to regulate these cellular activities in ASM and were reported to be interrelated at certain points. This article aims to provide an overview of the signaling pathways/molecules involved in ASM hyperplasia as well as the mapping of the interplay/crosstalk between these major pathways in mediating ASM hyperplasia. A more comprehensive understanding of the complexity of cellular signaling in ASM cells will enable more specific and safer drug development in the control of asthma.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  7. Fulltext Intracellular Delivery of siRNAs Targeting AKT and ERBB2 Genes Enhances Chemosensitization of Breast Cancer Cells in a Culture and Animal Model
    Fatemian T, Moghimi HR, Chowdhury EH
    Pharmaceutics, 2019 Sep 03;11(9).
    PMID: 31484456 DOI: 10.3390/pharmaceutics11090458
    : Pharmacotherapy as the mainstay in the management of breast cancer suffers from various drawbacks, including non-targeted biodistribution, narrow therapeutic and safety windows, and also resistance to treatment. Thus, alleviation of the constraints from the pharmacodynamic and pharmacokinetic profile of classical anti-cancer drugs could lead to improvements in efficacy and patient survival in malignancies. Moreover, modifications in the genetic pathophysiology of cancer via administration of small nucleic acids might pave the way towards higher response rates to chemotherapeutics. Inorganic pH-dependent carbonate apatite (CA) nanoparticles were utilized in this study to efficiently deliver various classes of therapeutics into cancer cells. Co-delivery of drugs and genetic materials was successfully attained through a carbonate apatite delivery device. On 4T1 cells, siRNAs against AKT and ERBB2 plus paclitaxel or docetaxel resulted in the largest increase in anti-cancer effects compared to CA/paclitaxel or CA/docetaxel. Therefore, these ingredients were selected for further in vivo investigations. Animals receiving injections of CA/paclitaxel or CA/docetaxel loaded with siRNAs against AKT and ERBB2 possessed significantly smaller tumors compared to CA/drug-treated mice. Interestingly, synergistic interactions in target protein knock down with combinations of CA/AKT/paclitaxel, CA/ERBB2/docetaxel were documented via western blotting.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  8. Human Papillomavirus Infection, p16INK4a Expression and Genetic Alterations in Vietnamese Cervical Neuroendocrine Cancer
    Van Ta T, Nguyen QN, Truong VL, Tran TT, Nguyen HP, Vuong LD
    Malays J Med Sci, 2019 Sep;26(5):151-157.
    PMID: 31728128 DOI: 10.21315/mjms2019.26.5.15
    Neuroendocrine cervical cancer is a rare subtype of cervical cancer with a highly aggressive malignancy. This study was conducted to analyse the human papillomavirus (HPV) infection and molecular abnormalities in Vietnamese neuroendocrine carcinomas of the uterine cervix. HPV genotyping and p53 mutations were examined using polymerase chain reaction (PCR)-based direct sequencing. Mutations of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF) were identified using commercial kits. Four high-risk HPV genotypes were identified in 26 (86.7%) out of a total of 30 tumours. The prevalence of HPV 16, 18, 31 and 45 was 20.0%, 50.0%, 20.0% and 36.7%, respectively. Overexpression of p16INK4a was observed in 93.3% of cases and was significantly correlated with high-risk HPV infections. Furthermore, p53 and NRAS mutations were detected in five (16.7%) and one (3.3%) cases, respectively, whereas no EGFR, KRAS or BRAF mutations were observed. These results demonstrate that high-risk HPV infection may be an important oncogenic factor for the development and progression of cervical neuroendocrine carcinoma.
    Matched MeSH terms: Proto-Oncogene Proteins B-raf
  9. Fulltext Induction of apoptosis and role of paclitaxel-loaded hyaluronic acid-crosslinked nanoparticles in the regulation of AKT and RhoA
    Chaudhry GE, Akim A, Zafar MN, Abdullah MA, Sung YY, Muhammad TST
    J Adv Pharm Technol Res, 2020 07 14;11(3):101-106.
    PMID: 33102192 DOI: 10.4103/japtr.JAPTR_26_20
    Cancer is a complex multifactorial disease and leading causes of death worldwide. Despite the development of many anticancer drugs, there is a reduced survival rate due to severe side effects. The nontargeted approach of convention drugs is one of the leading players in context to toxicity. Hyaluronan is a versatile bio-polymer and ligand of the receptor (CD44) on cancer cells. The MCF-7 and HT-29 cancer cell lines treated with hyaluronic acid-paclitaxel (HA-PTX) showed the distinguishing morphological features of apoptosis. Flow cytometric analysis showed that HA-PTX induces apoptosis as a significant mode of cell death. The activation level of tumor suppressor protein (p53) increased after PTX treatment in MCF-7, but no changes observed in HT-29 might be due to hereditary mutations. The lack of suppression in AKT and Rho A protein suggest the use of possible inhibitors in future studies which might could play a role in increasing the sensitivity of drug towards mutated cells line and reducing the possibilities for cancer cell survival, migration, and metastasis.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  10. Fulltext Expression of fibroblast growth factor receptor 4 (FGFR-4) in nasopharyngeal carcinoma (NPC) cell lines and its potential as therapeutic target
    Hooi Yeen Yap, Jack Bee Chook, Sin Yeang Teow
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):49-49.
    MyJurnal
    ntroduction: Nasopharyngeal carcinoma (NPC) is a prevalent cancer among human population in Southern China, Hong Kong and Southeast Asia. In Malaysia, NPC is the fourth most common cancer in both sexes, predominantly in the Chinese. Epstein-Barr virus (EBV) infection is known to be highly associated with NPC. Fibroblast growth factor receptor-4 (FGFR4) is part of the family of tyrosine kinase receptors that regulate cell survival, differentiation and pro-liferation. The binding of FGFR4 ligands such as fibroblasts growth factors (FGFs) has been shown to activate various oncogenic signalling pathway including MAPK, Ras and PI3K-Akt pathways. In the past, FGFR4 has been shown to promote tumorigenesis and tumour progression in various cancers such as liver, colon, breast and pancreatic and gastric cancers. However, its role in NPC establishment and pathogenesis is under-explored. This study aimed to evaluate the FGFR4 expression in NPC using various cell lines and its potential as a therapeutic target for NPC treat-ment by gene silencing. Methods: The basal FGFR4 level of NPC (EBV-positive: C666-1 and EBV-negative: HONE1 and HK1) and nasopharyngeal epithelial (NPE) normal (NP69 and NP460) cell lines was determined by western blot analysis and RT-qPCR. FGFR4 level at different time points (0, 24, 48, and 72 hours) in HONE1 and C666-1 cell lines were determined by western blot analysis. Luminescence-based assay was performed to determine the cell prolifer-ation of NPC cells in correlation with the FGFR4 expression. NPC cells were then treated with the optimised FGFR4 siRNA or FGFR inhibitor, BLU-9931 and the silencing/ inhibition of FGFR4 expression was confirmed by western blot analysis. The effect of FGFR4 inhibition on the cell proliferation and aggressiveness of NPC cells was then investigat-ed through wound healing assay and invasion marker analysis. Results: Out of the five tested cell lines, HONE1 and C666-1 highly expressed FGFR4, NP69 showed very low expression while HK1 and NP460 did not express FGFR4. In the time-point study, the FGFR4 level of HONE1 and C666-1 peaked at 24-48 hours which is the exponential phase of cells. Following that, the FGFR4 level decreased corresponding to the decreased cell growth rate due to the nutrient deprivation. siRNA experiments showed that 6.25nM of four siRNAs (5, 6, 9 and 10) could effectively target and silence the FGFR4 expression of HONE1, but not in C666-1 even up to 250nM was tested. When BLU-9931 was used, only modest inhibition was observed in both cells at 3uM. Compared to the untreated control, FGFR4-inhibited HONE1 exhibited decreased cell proliferation rate. Cell migration and invasion capabilities of HONE1 were also significantly reduced following the FGFR4 silencing, suggesting the potential of utilising FGFR4 as the therapeutic target. Conclusion: FGFR4 is highly expressed in C666-1 (EBV-positive) and HONE1 (initially EBV-positive, but lost EBV genome in subsequent in vitro passage) NPC cells, but not in EBV-negative HK1 NPC cell and normal NPE cells. FGFR4 gene silencing effectively inhibited the cell proliferation, migration and invasive potentials of NPC cell line. These findings highlight the therapeutic value of targeting FGFR4 for NPC treatment. Further investigations are war-ranted to reveal the molecular mechanism and the possible role of EBV in regulating FGFR4 pathway.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  11. Structural insight into tanapoxvirus mediated inhibition of apoptosis
    Suraweera CD, Anasir MI, Chugh S, Javorsky A, Impey RE, Hasan Zadeh M, et al.
    FEBS J, 2020 May 15.
    PMID: 32412687 DOI: 10.1111/febs.15365
    Premature programmed cell death or apoptosis of cells is a strategy utilized by multicellular organisms to counter microbial threats. Tanapoxvirus (TANV) is a large double-stranded DNA virus belonging to the poxviridae that causes mild Monkeypox-like infections in humans and primates. TANV encodes for a putative apoptosis inhibitory protein 16L. We show that TANV16L is able to bind to a range of peptides spanning the BH3 motif of human pro-apoptotic Bcl-2 proteins, and is able to counter growth arrest of yeast induced by human Bak and Bax. We then determined the crystal structures of TANV16L bound to three identified interactors, Bax, Bim and Puma BH3. TANV16L adopts a globular Bcl-2 fold comprising 7 a-helices, and utilizes the canonical Bcl-2 binding groove to engage pro-apoptotic host cell Bcl-2 proteins. Unexpectedly, TANV16L is able to adopt both a monomeric as well as a domain-swapped dimeric topology where the a1 helix from one protomer is swapped into a neighbouring unit. Despite adopting two different oligomeric forms, the canonical ligand binding groove in TANV16L remains unchanged from monomer to domain-swapped dimer. Our results provide a structural and mechanistic basis for tanapoxvirus mediated inhibition of host cell apoptosis, and reveal the capacity of Bcl-2 proteins to adopt differential oligomeric states whilst maintaining the canonical ligand binding groove in an unchanged state.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2
  12. Fulltext The Skeletal-Protecting Action and Mechanisms of Action for Mood-Stabilizing Drug Lithium Chloride: Current Evidence and Future Potential Research Areas
    Wong SK, Chin KY, Ima-Nirwana S
    Front Pharmacol, 2020;11:430.
    PMID: 32317977 DOI: 10.3389/fphar.2020.00430
    Lithium, the lightest natural-occurring alkali metal with an atomic number of three, stabilizes the mood to prevent episodes of acute manic and depression. Multiple lines of evidence point to lithium as an anti-suicidal, anti-viral, anti-cancer, immunomodulatory, neuroprotective and osteoprotective agent. This review article provides a comprehensive review of studies investigating the bone-enhancing effects of lithium and its possible underlying molecular mechanisms. Most of the animal experimental studies reported the beneficial effects of lithium in defective bones but not in healthy bones. In humans, the effects of lithium on bones remain heterogeneous. Mechanistically, lithium promotes osteoblastic activities by activating canonical Wingless (Wnt)/beta (β)-catenin, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and bone morphogenetic protein-2 (BMP-2) transduction pathways but suppresses osteoclastic activities by inhibiting the receptor activator of nuclear factor-kappa B (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and calcium signaling cascades. In conclusion, lithium confers protection to the skeleton but its clinical utility awaits further validation from human clinical trials.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  13. Fulltext N-Ethyl-n-Nitrosourea Induced Leukaemia in a Mouse Model through Upregulation of Vascular Endothelial Growth Factor and Evading Apoptosis
    Aliyu A, Shaari MR, Ahmad Sayuti NS, Reduan MFH, Sithambaram S, Noordin MM, et al.
    Cancers (Basel), 2020 Mar 13;12(3).
    PMID: 32183192 DOI: 10.3390/cancers12030678
    Chemical carcinogens are commonly used to investigate the biology and prognoses of various cancers. This study investigated the mechanism of leukaemogenic effects of n-ethyl-n-nitrosourea (ENU) in a mouse model. A total of 14 3-week-old male Institute of Cancer Research (ICR)-mice were used for the study. The mice were divided into groups A and B with seven mice each. Group A served as the control while group B received intraperitoneal (IP) injections of 80 mg/kg ENU twice with a one-week interval and were monitored monthly for 3 months for the development of leukaemia via blood smear examination. The mice were sacrificed humanely using a CO2 chamber. Blood, spleen, lymph nodes, liver, kidney and lung samples were collected for blood smear examination and histopathological evaluation. The expression of angiogenic protein (VEGF), and pro and anti-apoptotic proteins (BCL2 and BAX), was detected and quantified using Western blot technique. Leukaemia was confirmed by the presence of numerous blast cells in the peripheral blood smear in group B. Similarly, the VEGF and BCL2 proteins were significantly (p < 0.05) upregulated in group B compared to A. It is concluded that IP administration of 80 mg/kg ENU induced leukaemia in ICR-mice 12 weeks post administration through upregulation of angiogenic and anti-apoptotic proteins: VEGF and BCL2.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2
  14. Fulltext A Clinicopathologic Study of Seven Cases of Orbital Solitary Fibrous Tumours
    Ting XW, Sothiraghagan S, W Md Kasim WM, Muhammed J
    Cureus, 2020 May 24;12(5):e8259.
    PMID: 32596077 DOI: 10.7759/cureus.8259
    Objective To describe the patient demographics, clinical findings, investigations, surgical outcomes, and histopathological findings of seven cases of orbital solitary fibrous tumours. Method This was a retrospective review of seven cases of orbital solitary fibrous tumour, which were followed up in Hospital Serdang, a national oculoplastic centre, from years 2008-2017. Results This study included seven patients with ages between 21 and 35 years old; two were males and five were females. All seven patients presented with painless chronic unilateral proptosis. Radiological imaging of the orbit showed a localized contrast enhancing intraorbital mass. All patients underwent orbitotomy and excisional biopsy. Intraoperative findings showed a well-encapsulated and vascularized mass. Histological findings of spindle-shaped cells were noted. All cases had positive staining for cluster of differentiation (CD) 34, five were positive for CD 99, four were positive for B-cell lymphoma (BCL-2), and five patients had positive staining for S-100. Three of the patients did not have clear margins during the primary operation and subsequently had a recurrence within two years. Conclusion A solitary fibrous tumour is a rare mesenchymal tumour with a pleural origin. The orbit is the most common extrapleural site of the tumour and they are usually benign. Immunohistochemistry is important to differentiate it from other, more aggressive forms of orbital tumours. Regular follow-up is important to monitor for recurrence.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2
  15. Fulltext Germline TET2 loss of function causes childhood immunodeficiency and lymphoma
    Stremenova Spegarova J, Lawless D, Mohamad SMB, Engelhardt KR, Doody G, Shrimpton J, et al.
    Blood, 2020 Aug 27;136(9):1055-1066.
    PMID: 32518946 DOI: 10.1182/blood.2020005844
    Molecular dissection of inborn errors of immunity can help to elucidate the nonredundant functions of individual genes. We studied 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin. All 3 showed early autologous T-cell reconstitution following allogeneic hematopoietic stem cell transplantation. By whole-exome sequencing, we identified rare homozygous germline missense or nonsense variants in a known epigenetic regulator of gene expression: ten-eleven translocation methylcytosine dioxygenase 2 (TET2). Mutated TET2 protein was absent or enzymatically defective for 5-hydroxymethylating activity, resulting in whole-blood DNA hypermethylation. Circulating T cells showed an abnormal immunophenotype including expanded double-negative, but depleted follicular helper, T-cell compartments and impaired Fas-dependent apoptosis in 2 of 3 patients. Moreover, TET2-deficient B cells showed defective class-switch recombination. The hematopoietic potential of patient-derived induced pluripotent stem cells was skewed toward the myeloid lineage. These are the first reported cases of autosomal-recessive germline TET2 deficiency in humans, causing clinically significant immunodeficiency and an autoimmune lymphoproliferative syndrome with marked predisposition to lymphoma. This disease phenotype demonstrates the broad role of TET2 within the human immune system.
    Matched MeSH terms: Proto-Oncogene Proteins/deficiency*; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology
  16. Diosgenin, a steroidal saponin, and its analogs: Effective therapies against different chronic diseases
    Parama D, Boruah M, Yachna K, Rana V, Banik K, Harsha C, et al.
    Life Sci, 2020 Nov 01;260:118182.
    PMID: 32781063 DOI: 10.1016/j.lfs.2020.118182
    BACKGROUND: Chronic diseases are a major cause of mortality worldwide, and despite the recent development in treatment modalities, synthetic drugs have continued to show toxic side effects and development of chemoresistance, thereby limiting their application. The use of phytochemicals has gained attention as they show minimal side effects. Diosgenin is one such phytochemical which has gained importance for its efficacy against the life-threatening diseases, such as cardiovascular diseases, cancer, nervous system disorders, asthma, arthritis, diabetes, and many more.

    AIM: To evaluate the literature available on the potential of diosgenin and its analogs in modulating different molecular targets leading to the prevention and treatment of chronic diseases.

    METHOD: A detailed literature search has been carried out on PubMed for gathering information related to the sources, biosynthesis, physicochemical properties, biological activities, pharmacokinetics, bioavailability and toxicity of diosgenin and its analogs.

    KEY FINDINGS: The literature search resulted in many in vitro, in vivo and clinical trials that reported the efficacy of diosgenin and its analogs in modulating important molecular targets and signaling pathways such as PI3K/AKT/mTOR, JAK/STAT, NF-κB, MAPK, etc., which play a crucial role in the development of most of the diseases. Reports have also revealed the safety of the compound and the adaptation of nanotechnological approaches for enhancing its bioavailability and pharmacokinetic properties.

    SIGNIFICANCE: Thus, the review summarizes the efficacy of diosgenin and its analogs for developing as a potent drug against several chronic diseases.

    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  17. Fulltext Antileukemic Effect of Palladium Nanoparticles Mediated by White Tea (Camellia sinensis) Extract In Vitro and in WEHI-3B-Induced Leukemia In Vivo
    Othman H, Rahman H, Mohan S, Aziz S, Marif H, Ford D, et al.
    Evid Based Complement Alternat Med, 2020;2020:8764096.
    PMID: 32922508 DOI: 10.1155/2020/8764096
    This study investigated the in vivo antileukemic activity of palladium nanoparticles (Pd@W.tea-NPs) mediated by white tea extract in a murine model. The cell viability effect of Pd@W.tea-NPs, "blank" Pd nanoparticles, and white tea extract alone was determined in murine leukemia WEHI-3B cells and normal mouse fibroblasts (3T3 cells). Apoptotic and cell cycle arrest effects of Pd@W.tea-NPs in WEHI-3B cells were evaluated. The effects of Pd@W.tea-NPs administered orally to leukemic mice at 50 and 100 mg/kg daily over 28 days were evaluated. Pd@W.tea-NPs reduced the viability of WHEI-3B cells with IC50 7.55 μg/ml at 72 h. Blank Pd nanoparticles and white tea extract alone had smaller effects on WHEI-3B viability and on normal fibroblasts. Pd@W.tea-NPs increased the proportion of Annexin V-positive WHEI-3B cells and induced G2/M cell cycle arrest. Leukemic cells in the spleen were reduced by Pd@W.tea-NPs with an increase in Bax/Bcl-2 and cytochrome-C protein and mRNA levels indicating the activation of the mitochondrial apoptotic pathway. These effects replicated the effects of ATRA and were not observed using blank Pd nanoparticles. Pd@W.tea-NPs afford therapeutic efficacy against leukemia likely to pivot on activation of the mitochondrial pathway of apoptotic signaling and hence appear attractive potential candidates for development as a novel anticancer agent.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2
  18. An oncological curiosity of a male patient with a huge leiomyoma of the terminal ileum
    Zainudin S, Rajanthran SK, Azizan N, Hayati F, Ginawoi J, Suhaimi KA, et al.
    Oxf Med Case Reports, 2020 Oct;2020(10):omaa086.
    PMID: 33133619 DOI: 10.1093/omcr/omaa086
    Leiomyoma is a smooth muscle tumour that can arise in any part of the body especially the uterus. Even though it is traditionally linked with hormonal influence, it can also develop in extrauterine organs with a slight female predominance. It is indistinguishable with gastrointestinal stromal tumour (GIST) histologically. We report a case of a 30-year-old gentleman who presented with a huge painful mass in the right iliac fossa. Computed tomography revealed a 10 × 10 cm homogeneous mass arising from the terminal ileum; he subsequently underwent an open right hemicolectomy. Histology showed a well-circumscribed lesion composed of interlacing bundles of smooth muscle fibres of the submucosa with positive smooth muscle actin and H-Caldesmon stains but negative for DOG-1 and CD117 (c-kit) stains which were consistent with leiomyoma. Despite its rarity, this hormone-related tumour needs to be considered regardless of gender. Immunohistochemistry is paramount as it is histologically identical to GIST.
    Matched MeSH terms: Proto-Oncogene Proteins c-kit
  19. Fulltext Estrogen Receptors in Nonfunctioning Pituitary Neuroendocrine Tumors: Review on Expression and Gonadotroph Functions
    Haydar Ali Tajuddin A, Kamaruddin N, Sukor N, Azizan EA, Omar AM
    J Endocr Soc, 2020 Dec 01;4(12):bvaa157.
    PMID: 33241169 DOI: 10.1210/jendso/bvaa157
    Estrogen (17β-estradiol or E2) is a crucial regulator of the synthesis and secretion of pituitary reproductive hormones luteinizing hormone, follicle-stimulating hormone, and prolactin. In this review, we summarize the role of estrogen receptors in nonfunctioning pituitary neuroendocrine tumors (NF-Pitnets), focusing on immunoexpression and gonadotroph cell proliferation and apoptosis. Gonadotroph tumors are the most common subtype of NF-Pitnets. Two major estrogen receptor (ER) isoforms expressed in the pituitary are estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). Overall, estrogen actions are mostly exerted through the ERα isoform on the pituitary. The G protein-coupled estrogen receptor (GPER) located at the plasma membrane may contribute to nongenomic effects of estrogen. Nuclear immunoreactivity for ERα and ERβ was highest among gonadotroph and null cell tumors. Silent corticotroph tumors are the least immunoreactive for both receptors. A significantly elevated ERα expression was observed in macroadenomas compared with microadenomas. ERα and ERβ may act in opposite directions to regulate the Slug-E-cadherin pathway and to affect invasiveness of NF-Pitnets. In the cellular pathway, ERs regulate estrogen-induced proliferation and differentiation and impact several signaling pathways including the MAPK and PI3K/Akt pathway. Estrogen was the first-discovered inducer of pituitary tumor transforming gene 1 that was abundantly expressed in NF-Pitnets. ERα can be a potential biomarker for predicting tumor size and invasiveness as well as therapeutic target for NF-Pitnets. Selective estrogen receptor modulators or antiestrogen may represent as an alternative choice for the treatment of NF-Pitnets.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  20. Fulltext Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review
    Tan JN, Mohd Saffian S, Buang F, Jubri Z, Jantan I, Husain K, et al.
    Front Pharmacol, 2020;11:504624.
    PMID: 33328981 DOI: 10.3389/fphar.2020.504624
    Background:Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents. Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as "Gynura," "antioxidant," "anti-inflammatory," or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English. Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species. Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
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