scholarly journals Slt2-MAPK/RNS1 Controls Conidiation via Direct Regulation of the Central Regulatory Pathway in the Fungus Metarhizium robertsii

2021 ◽  
Vol 8 (1) ◽  
pp. 26
Author(s):  
Yamin Meng ◽  
Xingyuan Tang ◽  
Yuting Bao ◽  
Mingxiang Zhang ◽  
Dan Tang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Signaling ◽  
Regulatory Pathway ◽  
Term Survival ◽  
Metarhizium Robertsii ◽  
Ascomycete Fungi ◽  
The One ◽  
Brla Gene ◽  
Small Hydrophobic

Ascomycete fungi usually produce small hydrophobic asexual conidia that are easily dispersed and essential for long-term survival under a variety of environmental conditions. Several upstream signaling regulators have been documented to control conidiation via regulation of the central regulatory pathway that contains the transcription factors BrlA, AbaA and WetA. Here, we showed that the Slt2-MAPK signaling pathway and the transcription factor RNS1 constitute a novel upstream signaling cascade that activates the central regulatory pathway for conidiation in the Ascomycetes fungus M. robertsii. The BrlA gene has two overlapping transcripts BrlAα and BrlAβ; they have the same major ORF, but the 5’ UTR of BrlAβ is 835 bp longer than the one of BrlAα. During conidiation, Slt2 phosphorylates the serine residue at the position 306 in RNS1, which self-induces. RNS1 binds to the BM2 motif in the promoter of the BrlA gene and induces the expression of the transcript BlrAα, which in turn activates the expression of the genes AbaA and WetA. In conclusion, the Slt2/RNS1 cascade represents a novel upstream signaling pathway that initiates conidiation via direct activation of the central regulatory pathway. This work provides significant mechanistic insights into the production of asexual conidia in an Ascomycete fungus.

scholarly journals Effects of Maternal Chromium Restriction on the Long-Term Programming in MAPK Signaling Pathway of Lipid Metabolism in Mice

Nutrients ◽  
2016 ◽  
Vol 8 (8) ◽  
pp. 488 ◽  
Author(s):  
Qian Zhang ◽  
Xiaofang Sun ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals A Potential Mechanism of Tumor Progression during Systemic Infections Via the Hepatocyte Growth Factor (HGF)/c-Met Signaling Pathway

2020 ◽  
Vol 9 (7) ◽  
pp. 2074 ◽  
Author(s):  
Hironori Tsujimoto ◽  
Hiroyuki Horiguchi ◽  
Yusuke Matsumoto ◽  
Risa Takahata ◽  
Nariyoshi Shinomiya ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Metastasis ◽  
Hepatocyte Growth Factor ◽  
Liver Metastases ◽  
Signaling Pathway ◽  
Tumor Cells ◽  
High Serum ◽  
Term Survival ◽  
Hepatocyte Growth

Background: Increasing evidence has demonstrated that postoperative infectious complications (PICs) after digestive surgery are significantly associated with negative long-term outcomes; however, precise mechanisms of how PICs affect the poor long-term survival remain unclear. Here, we focused on the hepatocyte growth factor (HGF)/c-Met signaling pathway as one of those mechanisms. Methods: In the clinical setting, serum HGF levels were measured in the patients with sepsis and those with PICs after undergoing esophagectomy. Using a liver metastasis mouse model with cecal ligation and puncture (CLP), expressions of HGF and the roles of the HGF/c-Met pathway in the progression of tumor cells were examined. Results: Serum HGF levels were very high in the patients with intra-abdominal infection on postoperative days (PODs) 1, 3, and 5; similarly, compared to the patients without PICs, those with PICs had significantly higher serum HGF levels on 1, 3, and 5 days after esophagectomy. The patients with PICs showed poorer overall survival than those without PICs, and the patients with high serum HGF levels on POD 3 showed poorer prognosis than those with low HGF levels. Similarly, at 24 and 72 h after operation, serum levels of HGF in CLP mice were significantly higher than those in sham-operated mice. Intraperitoneal injection of mouse recombinant HGF significantly promoted liver metastases in sham-operated mice on 14 days after surgery. Knocking down c-Met expression on NL17 tumor cells by RNAi technology significantly inhibited the promotion of CLP-induced liver metastases. Conclusions: Infections after surgery increased serum HGF levels in the clinical as well as experimental settings. Induction of high serum HGF levels by CLP promoted liver metastases in a murine liver metastasis model, suggesting the involvement of the HGF/c-Met signaling pathway in tumor promotion mechanisms. Thus, targeting the HGF/c-Met signaling pathway may be a promising approach for malignant tumors, particularly in the patients with PICs.

scholarly journals Reduction in ovulation or male sex phenotype increases long-term anoxia survival in a daf-16-independent manner in Caenorhabditis elegans

2009 ◽  
Vol 36 (3) ◽  
pp. 167-178 ◽  
Author(s):  
Alexander R. Mendenhall ◽  
Michelle G. LeBlanc ◽  
Desh P. Mohan ◽  
Pamela A. Padilla
Keyword(s):  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Oocyte Maturation ◽  
Germ Line ◽  
Physiological State ◽  
Mapk Signaling ◽  
Oxygen Deprivation ◽  
Progeny Production ◽  
Independent Manner

Identifying genotypes and phenotypes that enhance an organism's ability to survive stress is of interest. We used Caenorhabditis elegans mutants, RNA interference (RNAi), and the chemical 5-fluorodeoxyuridine (FUDR) to test the hypothesis that a reduction in progeny would increase oxygen deprivation (anoxia) survival. In the hermaphrodite gonad, germ line processes such as spermatogenesis and oogenesis can be simultaneously as well as independently disrupted by genetic mutations. We analyzed genetic mutants [ glp-1(q158), glp-4(bn2ts), plc-1(rx1), ksr-1(ku68), fog-2(q71), fem-3(q20), spe-9(hc52ts), fer-15(hc15ts)] with reduced progeny production due to various reproductive defects. Furthermore, we used RNAi to inhibit the function of gene products in the RTK/Ras/MAPK signaling pathway, which is known to be involved in a variety of developmental processes including gonad function. We determined that reduced progeny production or complete sterility enhanced anoxia survival except in the case of sterile hermaphrodites [ spe-9(hc52ts), fer-15(hc15ts)] undergoing oocyte maturation and ovulation as exhibited by the presence of laid unfertilized oocytes. Furthermore, the fog-2(q71) long-term anoxia survival phenotype was suppressed when oocyte maturation and ovulation were induced by mating with males that have functional or nonfunctional sperm. The mutants with a reduced progeny production survive long-term anoxia in a daf-16- and hif-1-independent manner. Finally, we determined that wild-type males were able to survive long-term anoxia in a daf-16-independent manner. Together, these results suggest that the insulin signaling pathway is not the only mechanism to survive oxygen deprivation and that altering gonad function, in particular oocyte maturation and ovulation, leads to a physiological state conducive for oxygen deprivation survival.

scholarly journals Non-Coding RNAs and Wnt/β-Catenin Signaling Pathway in Gastric Cancer: From EMT to Drug Resistance

Onco ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 140-157
Author(s):  
Bruno Takao Real Karia ◽  
Camila Albuquerque Pinto ◽  
Carolina Oliveira Gigek ◽  
Fernanda Wisnieski ◽  
Marilia Arruda Cardoso Smith
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Biological Processes ◽  
Therapeutic Approaches ◽  
Term Survival ◽  
The Third ◽  
The Past ◽  
Sequencing Technologies ◽  
Non Coding Rnas

Gastric cancer is one of the most common cancers and the third cause of cancer-related death worldwide. The treatment of GC patients improved due to advancements in surgery, radiotherapy and chemotherapy. However, the long-term survival rate of patients with gastric cancer remains around 20%. Thus, development of novel therapeutic approaches is of great interest, in order to reduce the need for mutilating surgeries and morbid adjuvant therapies. For many years, it was believed that the RNA was a mere intermediate molecule in the genetic information flow. However, during the past decades, with the advent of new sequencing technologies, it was revealed that non-coding RNAs play important roles in many different biological processes. The Wnt/β-catenin signaling pathway has been reported to regulate crucial events during neoplasic development, such as cell differentiation, proliferation, invasion, migration, apoptosis, and angiogenesis. In this review, we will focus on microRNAs and long non-coding RNAs that have been implicated in gastric cancer tumorigenesis via modulation of the Wnt/β-catenin signaling pathway, which provided some biomarkers to prognosis, diagnosis, and therapy.

scholarly journals The Flavonol Isoquercitrin Promotes Mitochondrial-Dependent Apoptosis in SK-Mel-2 Melanoma Cell via the PI3K/AKT/mTOR Pathway

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3683
Author(s):  
Yeong-Seon Won ◽  
Jeong-Ho Kim ◽  
Rona Camille M. Lizardo ◽  
Hye-Ji Min ◽  
Hyun-Dong Cho ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Morphological Analysis ◽  
Human Keratinocytes ◽  
Melanoma Cells ◽  
Cycle Phase ◽  
Term Survival ◽  
Anti Cancer ◽  
Induced Apoptosis ◽  
Phase Population

Isoquercitrin (IQ), a major flavonol present in Prunus mume fruit, has gained much attention in recent studies because of its superior bioavailability and physiological effects. In this study, the anti-cancer mechanism of IQ against human melanoma, particularly its effect on the mitochondria-mediated apoptosis, was investigated. Treatment with IQ at 25 μM concentration effectively inhibited the proliferation of SK-MEL-2 skin cancer cells while the same concentration did not exhibit cytotoxicity against human keratinocytes HaCaT. Morphological analysis and clonogenic assay also showed that IQ can alter the growth and long-term survival of SK-MEL-2 cells. IQ also induced apoptosis in the melanoma cells as manifested in the nuclear morphology changes, DNA fragmentation, increase in the apoptosis rate (17.69% at 25 μM) and accumulation of sub-G1 cell cycle phase population (19.55% at 25 μM). Western blot analysis revealed the involvement of the mitochondrial apoptosis signaling pathway in the anti-cancer property of IQ. Treatment with IQ resulted in the decrease in the levels of procaspase-8 and -9, and Bcl-2 protein, and an increase in the expression of cleaved PARP and Bax. Moreover, AIF and Endo G protein expression increased, indicating a caspase-independent mitochondrial-mediated apoptosis. The anti-proliferative activity of IQ against SK-MEL-2 can also be attributed to the downregulation of the PI3K/AktmTOR signaling pathway. These findings showed that IQ can be developed into a chemopreventive therapeutic agent against the melanoma cells.

scholarly journals Combination With Glucocoriticoids and/or Immunosuppressants Brings Few Benefits in Patients With Primary Biliary Cholangitis

2021 ◽  
Author(s):  
Zilong Wang ◽  
Rui Jin ◽  
Mei Hao ◽  
Yandi Xie ◽  
Hao Wang ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Survival Rate ◽  
Triple Therapy ◽  
Primary Biliary Cholangitis ◽  
Term Survival ◽  
Long Term Survival ◽  
Significant Difference ◽  
One Year ◽  
The One

Abstract Objective To compare the efficacy of ursodeoxycholic acid (UDCA) monotherapy, and UDCA combined with glucocorticoids and/or immunosuppressants for patients with primary biliary cholangitis (PBC), and to search for relevant factors influencing the efficacy. Methods This retrospective study enrolled 266 patients who were initially diagnosed with PBC were grouped according to different treatment regimes. We analyzed and compared demographic characteristics, immune parameters, biochemistry profiles and other indicators collected at baseline, six months and one year of treatment. The prognosis was evaluated by Paris II standard and GLOBE score. T test, chi-square test and logistic regression were used for statistical analysis. Results According to Paris II standard and GLOBE score, there was no significant difference in one-year response rate and GLOBE score among the three treatment schemes (P > 0.05). GLOBE score > 0.3 indicated a decrease of the long-term survival rate, it was found that the long-term survival rate of the triple therapy group was significantly improved compared with the monotherapy group (p=0.005). Multivariate logistic regression analysis showed that PLT, ALP and ALB levels were risk factors for poor response. For the patients whose IgG levels were elevated but below twice upper limit of normal (ULN), the clinical benefit from combination therapy was not significant compared with monotherapy (p>0.05). Conclusion: Compared with monotherapy, the double therapy did not improve the one-year efficacy and long-term survival rate of PBC patients. However, triple therapy may improve the long-term survival rate of patients, although it does not significantly improve the one-year efficacy.

Selective Modulation of the BMP Signaling Pathway Has Distinct Effects on Long-Term In Vitro Maintenance of Primitive Hematopoietic Progenitors in Human Umbilical Cord Blood.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3162-3162
Author(s):  
Leah E. Colvin-Wanshura ◽  
Matthew S. Nelson ◽  
Elliot J. Stephenson ◽  
Shaukat A. Khan ◽  
Yonghong Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Bmp Signaling ◽  
Hematopoietic Progenitors ◽  
Short Term ◽  
Term Survival ◽  
Selective Modulation ◽  
In Vitro Maintenance

Abstract Factors responsible for long-term survival and proliferation of human hematopoietic stem cells (hHSC), and their mechanisms of action, remain to be defined. We previously showed that specific O-sulfated heparan sulfate (OS-HS) improves human long-term culture initiating cell (LTC-IC) maintenance for up to 5 wks in vitro. This is related to the ability of OS-HS to bind to and modulate the activity of heparin-binding cytokines on primitive hematopoietic progenitors (PHP). Recent studies indicate that bone morphogenetic proteins (BMPs) influence the development of embryonic hematopoiesis and also augment short-term survival and proliferation of hHSC. Since HS may modulate BMP activity, we examined how combinations of OS-HS, BMPs and specific BMP antagonists influence PHP in umbilical cord blood (UCB). First, we confirmed by real-time quantitative RT-PCR (qRT-PCR) that UCB CD34+ and/or CD34+/CD38− cells (using linear mRNA amplification) constitutively express transcripts for BMP-4 and its inhibitor Chordin, BMP receptors BMPR-IA, BMPR-IB, BMPR-II, AcvR-II and AcvR-IIB, downstream signaling proteins SMAD-1 and -5, and target genes upregulated by BMPs including Inhibitors of DNA binding (Id) proteins 1–4, and determined their relative levels of expression. BMP-4 upregulated Id2 expression 17-fold, confirming that the BMP signaling pathway is functionally active in CD34+ cells. Next, we demonstrated that OS-HS may protect BMP-4 from its inhibitors, using Western immunoblotting of immunoprecipitated proteins to show that direct binding of the antagonist Chordin to BMP-4 is inhibited by OS-HS in a dose-dependent manner. Finally, we examined the effect of exogenous supplementation with 6 BMPs, or inhibition of endogenous BMPs by 7 antagonists, on short-term (2 wk) and long-term (5 wk) LTC-IC maintenance in UCB CD34+/CD38− cells cultured in presence of OS-HS, Flt3-ligand and thrombopoietin. Long-term LTC-IC maintenance was enhanced by BMP-4 (LTC-IC maintenance: 164 +/− 11% compared to culture without BMP-4; P=0.0001) but reduced by BMP-2 or BMP-7 (P<0.005), whereas BMP-3 had no effect. In combination, BMP-3, -4 and -7 offset each other, with no net effect on LTC-IC maintenance. The simultaneous presence of BMPs 2–7 was markedly inhibitory to both short-term (56 +/− 11%; P=0.0018) and long-term (38 +/− 11%; P=0.0024) LTC-IC maintenance. Inhibition of endogenous BMPs by Noggin (which antagonizes BMP-2, -4 and -7 and GDF-5) most effectively enhanced long-term LTC-IC maintenance (320 +/− 36%; P=0.0002). In contrast, other antagonists that inhibit different groups of BMPs did not enhance long-term LTC-IC maintenance. These results indicate that (a) the BMP signaling pathway is expressed and functionally active in human PHP, (b) different members of the BMP family have distinct stimulatory or inhibitory effects on long-term LTC-IC maintenance, (c) endogenously expressed BMPs are extremely important modulators of long-term PHP maintenance, and (d) the ability of OS-HS to augment long-term in vitro PHP maintenance may be related to its effect on endogenous BMP activity. Our data suggest that selective modulation of BMP signaling may be essential for achieving long-term in vitro maintenance of human PHP. Ongoing studies are investigating how OS-HS affects BMP signaling, and the downstream effects of these molecules on target genes that influence stem cell decisions and fate.

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