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singaling pathway

Sumant Arora, Steven Young, Sudha Kodali, Ashwani K Singal
Porphyrias are a group of metabolic disorders, which result from a specific abnormality in one of the eight enzymes of the heme biosynthetic pathway. These have been subdivided based on the predominant site of enzyme defect into hepatic and erythropoietic types and based on clinical presentation into acute neurovisceral and cutaneous blistering porphyrias. This review focuses on hepatic porphyrias, which include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), aminolevulinic acid dehydratase deficiency porphyria (ADP), and porphyria cutanea tarda (PCT)...
November 2016: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
Ashwani K Singal, Vijay H Shah
Acute alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active heavy alcohol use. Presenting with acute or chronic liver failure, a severe episode has a potential for 30 to 40% mortality at 1 month from presentation, if not recognized and left untreated. Alcoholic hepatitis patients need supportive therapy for abstinence and nutritional supplementation for those patients with markedly reduced caloric intake. Results of the recently published STOPAH (Steroids or Pentoxifylline for Alcoholic Hepatitis) Study showed only a benefit of corticosteroids on short-term mortality without any benefit of pentoxifylline...
February 2016: Seminars in Liver Disease
Wenjie Deng, Luo Gu, Xiaojie Li, Jianchao Zheng, Yujie Zhang, Biao Duan, Jie Cui, Jing Dong, Jun Du
BACKGROUND: CD24, a mucin-like membrane glycoprotein, plays a critical role in carcinogenesis, but its role in human gastric cancer and the underlying mechanism remains undefined. METHODS: The contents of CD24 and epidermal growth factor receptor (EGFR) in gastric cancer cells (SGC-7901 and BGC-823) and non-malignant gastric epithelial cells (GES-1) were evaluated by Western blotting assay. Cellular EGFR staining was examined by immunofluorescence assay. Cell migration rate was measured by wound healing assay...
February 1, 2016: Journal of Translational Medicine
Yanwei Liu, Sen Chen, Rui Xue, Juan Zhao, Maojun Di
Deregulation of PI3K/Akt/mTOR pathway has been recently identified to play a crucial role in the progress of human gastric cancer. In this study, we show that mefloquine, a FDA-approved anti-malarial drug, effectively targets human gastric cancer cells. Mefloquine potently inhibits proliferation and induces apoptosis of a panel of human gastric cancer cell lines, with EC50 ∼ 0.5-0.7 μM. In two independent gastric cancer xenograft mouse models, mefloquine significantly inhibits growth of both tumors. The combination of mefloquine with paclitaxel enhances the activity of either drug alone in in vitro and in vivo...
February 5, 2016: Biochemical and Biophysical Research Communications
Changbao Chen, Meng Zhao, Aixian Tian, Xiaolin Zhang, Zhi Yao, Xinlong Ma
Bone sarcomas such as osteosarcoma and chondrosarcoma are frequently refractory to conventional chemotherapy and radiotherapy that exhibit poor prognosis. The Wnt signaling are evolutionarily conserved and implicated in cell proliferation and sarcomagenesis. However, the potential role of the Wnt signaling in bone sarcomas is still unclear. Here we demonstrate aberrant activation of Wnt/β-catenin signaling in bone sarcoma cells, involving an autocrine Wnt signaling loop with upregulation of specific Wnt ligands and receptors...
July 10, 2015: Oncotarget
Xiucai Xu, Liuyuan He, Aimei Zhang, Qing Li, Wen Hu, He Chen, Jian Du, Jilong Shen
Congenital toxoplasmosis may result in abortion, severe mental retardation and neurologic damage in the offspring. Placental damage is considered as the key event in this disease. Here we show that maternal infection with Toxoplasma gondii Wh3 isolate of genotype Chinese 1, which is predominantly prevalent in China, induced trophoblast apoptosis of pregnant mouse. PCR array analysis of 84 key genes in the biogenesis and functions of mouse mitochondrion revealed that ten genes were up-regulated at least 2-fold in the Wh3 infection group, compared with those in the control...
July 2015: Experimental Parasitology
Chang-min Lin, Yan-ping Yuan, Xian-cai Chen, Hai-hong Li, Bo-zhi Cai, Yang Liu, Huan Zhang, Yu Li, Keng Huang
The rat whisker hair follicle (HF) is a model for studying the reconstruction of the HF or dermal papilla (DP), and involves the Wnt/β-catenin signaling pathway, which is a key pathway in HF development and HF cycling after birth. It has been reported that Wnt/catenin signaling plays an indispensable role in human or rat pelages development and postnatal growth. However, the distribution of some Wnt/β-catenin signaling pathway factors and their relationship with the epithelial stem cell markers in whisker follicles has not been characterized...
June 2015: Journal of Molecular Histology
Rajalaxmi Natarajan, Vinamrata Singal, Richard Benes, Junling Gao, Hoi Chan, Haijun Chen, Yongjia Yu, Jia Zhou, Ping Wu
Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs). In vitro hNSCs primed with fibroblast growth factor 2 (FGF2) exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF), which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs...
2014: PloS One
Ashwani K Singal, Charles Parker, Christine Bowden, Manish Thapar, Lawrence Liu, Brendan M McGuire
UNLABELLED: Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as hepatic or erythropoietic, depending upon the site where the gene defect is predominantly expressed. Clinical phenotypes are classified as follows: (1) acute porphyrias with neurovisceral symptoms: acute intermittent porphyria; delta amino-levulinic acid hydratase deficiency porphyria; hereditary coproporphyria; and variegate porphyria and (2) cutaneous porphyrias with skin blistering and photosensitivity: porphyria cutanea tarda; congenital erythropoietic porphyria; hepatoerythropoietic porphyria and both erythropoietic protoporphyrias: autosomal dominant and X-linked...
September 2014: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Matthew Zeglinski, Sheena Premecz, Jordyn Lerner, Piotr Wtorek, Megan Dasilva, Devin Hasanally, Rakesh Chaudhary, Anita Sharma, James Thliveris, Amir Ravandi, Pawan K Singal, Davinder S Jassal
BACKGROUND: Doxorubicin (DOX) and trastuzumab (TRZ) are highly effective chemotherapeutic agents in the breast cancer setting, limited by their cardiotoxic side effects. Among the potential mechanisms for this drug-induced cardiomyopathy, increased production of oxidative stress (OS) through a nitric oxide synthase 3 (NOS3)-dependent pathway has gained recent attention. The objective of the study was to determine the role of NOS3 and OS in a clinically relevant female murine model of DOX- and TRZ-induced heart failure...
March 2014: Canadian Journal of Cardiology
H B Singal, I S Sheoran, Randhir Singh
Activities of key enzymes of Calvin cycle and C4 metabolism, rate of (14)CO2 fixation in light and dark and the initial products of photosynthetic (14)CO2 fixation were determined in flag leaf and different ear parts of wheat viz. pericarp, awn and glumes. Compared to the activities of RuBP carboxylase and other Calvin cycle enzymes viz. NADP-glyceraldehyde-3-phosphate dehydrogenase, NAD-glyceraldehyde-3-phosphate dehydrogenase and ribulose-5-phosphate kinase, the levels of PEP carboxylase and other enzymes of C4 metabolism viz...
January 1986: Photosynthesis Research
Erik S Knudsen, Purva Gopal, Amit G Singal
Hepatocellular carcinoma (HCC) represents one of the leading causes of cancer death and has proved to be highly refractory to treatment. Extensive analysis of the disease has demonstrated that it arises predominantly in response to high-risk etiological challenges, most notably hepatitis virus. However, with evolving vaccination and the obesity epidemic, progressively more cases are associated with underlying metabolic dysfunction. Pathologically diverse forms of HCC are observed, and recent sequencing analysis has defined common events that target well-known cancer pathways including β-catenin/Axin, TP53, and RB/CDKN2A, as well as frequent aberrations in chromatin remodeling factors...
March 2014: American Journal of Pathology
Binbin Yan, Reetu D Singla, Latifa S Abdelli, Pawan K Singal, Dinender K Singla
Thymosin β4 (Tβ4), a small G-actin sequestering peptide, mediates cell proliferation, migration, and angiogenesis. Whether embryonic stem (ES) cells, overexpressing Tβ4, readily differentiate into cardiac myocytes in vitro and in vivo and enhance cardioprotection following transplantation post myocardial infarction (MI) remains unknown. Accordingly, we established stable mouse ES cell lines, RFP-ESCs and Tβ4-ESCs, expressing RFP and an RFP-Tβ4 fusion protein, respectively. In vitro, the number of spontaneously beating embryoid bodies (EBs) was significantly increased in Tβ4-ESCs at day 9, 12 and 15, compared with RFP-ESCs...
2013: PloS One
Muhammad Faraz Arshad Malik, Lin Ye, Wen G Jiang
Plexins are transmembrane protein receptors for semaphorin molecules. These molecules are involved in numerous cellular activities related to cell proliferation, adhesion along with the basement membrane, cellular motility and invasive capability. All nine members of Plexins identified in vertebrates have been grouped into subclasses, termed Plexin-A, Plexin-B, Plexin-C and Plexin-D. Plexin-B consists of three members, namely Plexin-B1, Plexin-B2 and Plexin-B3. Plexin-B1 functionally interacts with Sema4A (Yukawa et al...
2014: Histology and Histopathology
Xian-Lin Wu, Da-Hong Ju, Jia Chen, Bin Yu, Kang-Li Liu, Jin-Xiong He, Cong-Qi Dai, Sha Wu, Zhou Chang, You-Ping Wang, Xiao-Yin Chen
Patchouli alcohol (PA) is a kind of methanol extracted from traditional Chinese medicine Pogostemonis Herba. Our research aimed to observe the anti-influenza virus role of PA in vitro. 16HBE (human respiratory epithelial cell) was infected by H1N1 (A/FM1/1/47) to set the cell model. Then the 16HBE was co-cultivated with three kinds of immune cells: dendritic cells, macrophages, and monocytes, PA (the concentration is 10 μg/mL) was added as a treatment intervention for 24 h. The immune cells and the supernate were collected for RT-PCR and ELISA detection related to RLH (RIG-1-like helicases) pathway...
October 2013: Current Microbiology
Ming-song Fan, Zi-yan Jiang, Yan-fen Zou, Lin Qu, Xue Zhou, Li-zhou Sun
OBJECTIVE: To investigate the effect of transforming growth factor β1 (TGF-β1) on the expression of matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), nuclear factor kappa B (NF-κB) and the possible signalling pathways in human amniotic cells WISH. METHODS: The WISH cell line was cultured. WISH cells were added with TGF-β1 of different concentrations (0, 2, 10 and 20 ng/ml, respectively) for 24 hours. Then, reverse transcription (RT) PCR and western blotting were used to analyze the protein and mRNA expression of TIMP-1 and MMP-9; and the expression of NF-κB was analyzed by western blot...
January 2013: Zhonghua Fu Chan Ke za Zhi
Li Yuan, Jing Wang, Haifang Xiao, Wanqiang Wu, Yutang Wang, Xuebo Liu
Isoorientin (ISO) (CAS RN: 4261-42-1) is a flavonoid compound that can be extracted from several plant species, such as Phyllostachys pubescens, Patrinia, and Drosophyllum lusitanicum. ISO is able to induce apoptosis through mitochondrial dysfunction and inhibition of PI3K/Akt signaling pathway in HepG2 cells, however, the effects of ISO on MAPK signaling pathways remain unknown. The present study investigated the effects of ISO on this pathway, and the roles of MAPK kinases on mitochondrial-mediated apoptosis in HepG2 cells...
March 2013: Food and Chemical Toxicology
Mazen Shaheen, Yaser Cheema, Atta U Shahbaz, Syamal K Bhattacharya, Karl T Weber
Congestive heart failure (CHF), a common clinical syndrome, has reached epidemic proportions. Its disabling symptoms account for frequent hospitalizations and readmissions. Pathophysiological mechanisms that lead to CHF and account for its progressive nature are of considerable interest. Important scientific observations obtained from Dr Pawan K Singal's laboratory in Winnipeg, Manitoba, have provided crucial insights to our understanding of the pathophysiological factors that contribute to cardiomyocyte necrosis (the heart is a postmitotic organ incapable of tolerating an ongoing loss of these cells without adverse functional consequences)...
2011: Experimental and Clinical Cardiology
Matthew Zeglinski, Ana Ludke, Davinder S Jassal, Pawan K Singal
Trastuzumab (Trz) is a monoclonal antibody against the human epidermal growth factor receptor 2 that is found to be overexpressed in 25% to 30% of breast cancer patients. In spite of the therapeutic benefits of Trz, cardiotoxic side effects are still an issue. This effect is potentiated particularly when Trz is administered following doxorubicin (DOX) treatment. Among the various mechanisms that may account for DOX and Trz-induced cardiotoxicity, the role of oxidative stress has gained significant support. The present review discusses the evidence supporting the hypothesis that oxidative stress comes from multiple sources through an increase in the production of reactive oxygen species and/or a decrease in antioxidant defense systems...
2011: Experimental and Clinical Cardiology
Mei-Jie Liu, Yan Li, Jing-Hua Pan, Hong Liu, Shao-Jun Wang, Jing-Ru Teng, Hong-Yan Zhao, Da-Hong Ju
OBJECTIVE: To reveal the mechanism of Zuogui Pill (see text) in treatment of glucocorticoid-induced osteoporosis from the angle of the Wnt signal transduction pathway and to provide further experimental evidence for expounding the scientific connotation of "the kidney dominating the bones" in TCM. METHODS: Forty-two male Wistar rats were selected and randomly divided into three groups, control group (n = 12), model group (n = 15) and Zuogui Pill group (n = 15). Form the beginning, The rats were injected dexamethasone for eight weeks to make the model of osteoporosis, and the Zuogui Pill were administered intragastrically to the rats of Zuogui Pill group for eight weeks...
June 2011: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
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