Strongly induces expression vivo inhibitory. Medical search. Frequent questions

This study is the first to show that VALD-3 induces apoptosis and cell cycle arrest in human breast cancer cells by suppressing Wnt/β-catenin signaling, indicating that it could be a potential drug for the treatment of breast cancer. (researchsquare.com)
Lycorine inhibited proliferation of various PCa cell lines, induced cell apoptosis and cell death. (oncotarget.com)

This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. (anti-agingfirewalls.com)
Using pharmacological approaches along with in vitro and in vivo experiments, we found that Nogo-A/NgR1 signaling regulates the pace of neuronal neogeneration by reducing NSC proliferation. (jneurosci.org)
Her research interests include the preparation and design of materials and scaffolds for in vitro and in vivo fundamental studies, and a further focus is the provision of useful tools to assess mechanisms that govern cell behavior in regenerative medicine. (ibecbarcelona.eu)

Of note, an increased carbohydrate uptake and/or induction of death receptors of cancer cells was exploited to develop glycoconjugates that potentially induce cellular stress, ROS and apoptosis. (degruyter.com)
NK cells recognize the targets through the biased signals transmitted from active or inhibitory receptors. (biomedcentral.com)

Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. (hindawi.com)
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-test was used to observe the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells induced on VALD-3. (researchsquare.com)
SFK inhibition also induced muscle differentiation in RMS cells by affecting the NOTCH3 receptor-p38 mitogen-activated protein kinase (MAPK) axis, which regulates the balance between proliferation and differentiation. (oncotarget.com)
and promoted the proliferation and invasiveness of breast cancer cells both in vivo and in vitro. (cancerindex.org)
Additionally, DBC1 knockdown eliminated the up-regulation of MMP7, EMT-related proteins, and cell cycle-related proteins as well as the enhanced proliferation and invasiveness induced by ZNF326. (cancerindex.org)
Knockdown of KDM1B inhibits cell proliferation and induces apoptosis of pancreatic cancer cells. (cancerindex.org)
bronchoalveolar lavage cells from control and CBD subjects to evaluate the beryllium salt-specific production of endogenous IL-10 and the effects of exogenous human rIL-10 (rhIL-10) on HLA expression, on the production of IL-2, IFN- , and TNF- , and on T lymphocyte proliferation. (cdc.gov)
exogenous rhIL-10 has a limited effect on cytokine production and no effect on T lymphocyte proliferation or HLA expression. (cdc.gov)
We of both mitogen- and Ag-induced accessory cell-dependent T lym- phocyte proliferation. (cdc.gov)

KP-induced C. albicans oxidative stress response and membrane permeability were also analysed. (unipi.it)

Moreover, APE (2.6 and 5.2 g/kg) decreased the elevation of TGF‑β1, α‑SMA, collagen I and collagen III expression, inhibited Smad2/3 phosphorylation as well as elevated the expression of the TGF‑β1 inhibitor Smad7. (spandidos-publications.com)
HGF c Met signaling can induce paxillin phosphorylation at its tyrosine residue, which in turn promotes tumor progression by enhancing tumor cell migration and spread.ten Activating c Met mutations are already proven to increase paxillin phosphorylation in SCLC.5 Furthermore, paxillin has become proven to be very expressed, and its gene from time to time amplified or mutated in NSCLC 11. (hormonespathway.com)
In Arabidopsis , the shade-induced de-phosphorylation of the transcription factor PIF7 (PHYTOCHROME-INTERACTING FACTOR 7) is the key event linking light perception to stem elongation. (elifesciences.org)
Here, we show that shade light induces the de-phosphorylation and nuclear accumulation of PIF7. (elifesciences.org)
Phosphorylation-resistant site mutations in PIF7 result in increased nuclear localization and shade-induced gene expression, and consequently augment hypocotyl elongation. (elifesciences.org)
Blocking the interaction between PIF7 and 14-3-3 proteins or reducing the expression of 14-3-3 proteins accelerates shade-induced nuclear localization and de-phosphorylation of PIF7, and enhances the shade phenotype. (elifesciences.org)

Protein and gene expression of apoptotic signaling pathway-related proteins such as caspase-3, cytochrome c, and PARP were determined to provide evidence for the mechanisms of action of Tan IIA in the treatment of psoriasis. (hindawi.com)
To enhance vaccine potency and improve thus responses to ICI, we analyzed the gene expression profile of an immunosuppressive dendritic cell (DC) population induced during vaccination, with the goal of identifying druggable inhibitory mechanisms. (unav.edu)
While transformation procedures have become routine for a growing number of plant species, the random introduction of complex transgenenic DNA into the plant genome by current methods generates unpredictable effects on both transgene and homologous native gene expression. (bioone.org)
Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository. (cancerindex.org)

In vivo , combined ibudilast and TMZ treatment of a patient derived xenograft (PDX) model resulted in significantly longer overall survival. (nature.com)

It inhibits peripheral nerve injury-induced spinal microgliosis, spinal microglial and astrocytic activation, and exhibits a powerful neuroprotective effect by preventing the induction of ATF3 + neurons following nerve ligation, consequently reducing the expression of chemokine MCP-1 in damaged neurons. (biomedcentral.com)
We show that in poly-(I:C)-stimulated HaCaT cells, CBD elevates the levels of AEA and dose-dependently inhibits poly-(I:C)-induced release of MCP-2, interleukin-6 (IL-6), IL-8, and tumor necrosis factor- α in a manner reversed by CB 2 and TRPV1 antagonists 6-iodopravadoline (AM630) and 5′-iodio-resiniferatoxin (I-RTX), respectively, with no cytotoxic effect. (aspetjournals.org)

SI221, which showed to be mainly effective against the SFK member YES, significantly reduced cell viability and induced apoptosis, without affecting non-tumor cells, such as primary human skin fibroblasts and differentiated C2C12 cells. (oncotarget.com)
In vivo studies further confirmed the inhibitory effect of celastrol on the expression of HIF-1α proteins, leading to a decreased growth of Hep3B cells in a xenograft tumor model. (spandidos-publications.com)
Inspired by the accidental discoveries, we constructed a NK-92 cell strain with high expression of GPX4 and treated the humanized xenograft tumor mice model with the NK-92 cells. (biomedcentral.com)
and F3, a poorly water-soluble polysaccharide and protein) were added to MA-10 mouse Leydig tumor cells with or without human chorionic gonadotropin (hCG), and the production of steroid and the expression of steroidogenic acute regulatory protein (StAR) were examined. (simpsonbiotech-usa.com)

HUVECs were administrated with TMZ or TMZ and lentivirus, the expression of EndMT and related proteins was observed by wound healing assay, immunoblotting, and immunofluorescence. (dovepress.com)
The expression of pro-apoptotic proteins and anti-apoptotic proteins in MCF-7 and MDA-MB-231 cells was investigated by Western blotting. (researchsquare.com)
Western blot analysis revealed that VALD-3 upregulated pro-apoptotic proteins (Bad and Bax), downregulated anti-apoptotic proteins (Bcl-2, Bcl-xl, survivin and XIAP) and increased the expression of cleaved caspase-3, cleaved caspase-8, Cyto-c and cleaved PARP. (researchsquare.com)
The expression of transforming growth factor‑β/Smad pathway proteins, α‑smooth muscle actin (α‑SMA), collagen I and collagen III was observed in fibrotic livers using western blot analysis. (spandidos-publications.com)
The aim of this selleck chemicals llc study was to assess the expression patterns of these three functionally relevant proteins, PAX5, c Met and paxillin, in the setting of neuroendocrine tumors with the lung. (hormonespathway.com)
Western blot assessment confirmed that myc tagged human SOD1 proteins were induced by doxycycline in these cell lines. (hormonespathway.com)

A triple combination of the ferroptosis inducing natural compound withaferin A, the CXCR2 inhibitor SB225002 and α-PD-1 greatly improves survival of wild-type mice with liver tumours. (bmj.com)
Conclusion Our data highlight a context-specific ferroptosis-induced immune response that could be therapeutically exploited for the treatment of primary liver tumours and liver metastases. (bmj.com)
Further analysis revealed L-KYN induced ferroptosis in NK cells via an AHR-independent way. (biomedcentral.com)
Moreover, we found NK cells with higher GPX4 expression showed resistance to L-KYN induced ferroptosis. (biomedcentral.com)

Together with James P. Allison, who worked on another co-inhibitory receptor called cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4), Tasuku Honjo was awarded the Nobel Prize in Physiology or Medicine 2018 for the discovery of cancer therapy by inhibition of negative immune regulation ( Wolchok, 2018 ). (frontiersin.org)
Moreover, the release of these proinflammatory factors from the activated cells enhances LPS-induced cytotoxic activations [ 14 ] and develops a continuous cycle of inflammatory stimuli. (hindawi.com)

Celastrol showed a potent inhibitory activity against HIF-1 activation induced by hypoxia in various human cancer cell lines. (spandidos-publications.com)
In this study, we sought to investigate the effects of TGF-β1, a potent anti-inflammatory cytokine, in alleviating nerve injury-induced neuropathic pain in rats. (biomedcentral.com)
Most of the compounds showed potent inhibitory activity, with antrodin A being the most potent (IC50= 0.9 µg/mL). (simpsonbiotech-usa.com)

XAV939 treatment blocked Wnt3a- induced accumulation of b-catenin in HEK293 cells (Fig. 1c), indicating that the compound modulates Wnt signalling upstream of b-catenin. (plasignaling.com)
Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. (spandidos-publications.com)

Scope includes mutations and abnormal protein expression. (cancerindex.org)
Most environmentally induced resistance mechanisms involve tandem repeats (TRs) in the promoter region of cyp51A coupled with nonsynonymous mutations, TR 34 /L98H and TR 46 /Y121F/T289A ( 1 ). (cdc.gov)
However, in vivo resistance development has primarily been associated with nonsynonymous mutations in cyp51A -inducing amino acid substitutions of hot spots (e.g. (cdc.gov)

also, biofilm-related genes expression was significantly reduced. (unipi.it)
DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. (cancerindex.org)
NF-κB activation by fluid flow, leading to expression of target genes such as E-selectin, ICAM-1, and VCAM-1, may regulate early monocyte recruitment and fatty streak formation. (rupress.org)

main text % % \newpage{} \linenumbers \section*{Introduction} %----------------------------------- \label{Introduction} Successful immunotherapy (IT) of IgE-mediated allergic disease is defined clinically as a long-lasting diminution of immediate hypersensitivity, \emph{i.e.}, greater tolerance, that is induced by repeated antigen exposure over a relatively long time period (\emph{e.g.} weeks-to-months). (openwetware.org)

RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)

TGF-β1 treatment also suppresses nerve injury-induced inflammatory response in the spinal cord, as revealed by a reduction in cytokine expression. (biomedcentral.com)
An early, transient and robust reaction of microglia is required for initiation of nerve injury-induced hyperalgesia, since they not only phagocytose cellular materials but also produce and secrete pro-inflammatory molecules that evoke an increase in neuronal activity of the spinal cord dorsal horn [ 13 ]. (biomedcentral.com)
ance in the timing or production of these cytokines, resulting in IL-10 is a key inhibitory cytokine in the inflammatory response tissue damage and disease. (cdc.gov)

RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.com)

TGF-β has been reported to trigger the activation of hepatic stellate cells (HSCs), inducing their differentiation into fibroblasts. (spandidos-publications.com)
Specifically, the employment of BC-Ppy compositesdrives partial H9c2 differentiation toward a cardiomyocyte-like phenotype.The scaffolds increase the expression of functional cardiac markersin H9c2 cells, indicative of a higher differentiation efficiency,which is not observed with plain BC. (ibecbarcelona.eu)

Flow-induced NF-κB activation is downstream of conformational activation of integrins, resulting in new integrin binding to the subendothelial extracellular matrix and signaling. (rupress.org)

The present study aimed to investigate the hepatoprotective effect of APE on CCl4‑induced hepatic fibrosis in rats. (spandidos-publications.com)
0.0417dl · g -1, Cp=0.2663 cal/(g · °C). The hepatoprotective effect of ACN2a was evaluated using a mouse model of hepatic injury that was induced by Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS). (simpsonbiotech-usa.com)
The administration of ACN2a (0.4, 0.8 g/kg/d, p.o.), significantly prevented increases in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activities in mice treated with P. acnes-LPS, indicating hepatoprotective activity in vivo. (simpsonbiotech-usa.com)

Also, C. butyricum manifested a protective effect towards EHECinduced apoptosis in CEICs by modulating BAX and Bcl expression, and caspase activation followed by caspase inhibition. (srcinhibitors.com)
In conclusion, it's been clearly demonstrated from the current research that treatment with C. butyricum and its SCS resulted in inhibition of EHEC development and adherence, and alleviation of EHEC induced apoptosis coupled with attenuation of expression of pro apoptotic elements in CEICs. (srcinhibitors.com)
title{Protein Tyrosine Phosphatase Inhibition Mimics Fc$\varepsilon$RI-induced Anergy and Reveals the Immunomodulatory Role of Hydrogen Peroxide as a Signaling Molecule in Human Basophils\thanksref{grant}} %Really struggling with a title that captures this paper -- probably a bad sign! (openwetware.org)
Antrodin A was isolated as one of the constituents of A. cinnamomea and was also detected as an in vivo metabolite of the major constituent antrodin C. The mode of inhibition for antrodin A on HCV protease was revealed by a Lineweaver-Burk plot as competitive inhibition. (simpsonbiotech-usa.com)

Foxp3 is a specific marker of natural T regulatory cells (nTregs, a lineage of T cells) and adaptive/induced T regulatory cells (a/iTregs), also identified by other less specific markers such as CD25 or CD45RB. (wikipedia.org)
The Foxp3 gene is also known to convert naïve T-cells to Treg cells, which are capable of an in vivo and in vitro suppressive capabilities suggesting that Foxp3 is capable of regulating the expression of suppression-mediating molecules. (wikipedia.org)
In contrast, PD-L2 expression is more restricted and can be induced on hematopoietic cells such as DCs, B cells, and monocytes/macrophages. (frontiersin.org)
The LPS-induced expression of iNOS and cytokines in BV2 cells was suppressed by the constituents of Rhodiola rosea in a concentration-dependent manner. (hindawi.com)
Hoechst 33258 staining was performed to determine if VALD-3 induced apoptosis of MCF-7 and MDA-MB-231 cells and Annexin V/PI staining was performed to quantify the percentages of apoptosis. (researchsquare.com)
Flow cytometry analysis showed that VALD-3 triggered cell cycle arrest and induced apoptosis of breast cancer cells. (researchsquare.com)
XAV939 strongly inhibited Wnt3a-stimu- lated STF activity in HEK293 cells, but did not affect CRE, NF-kB or TGF-b luciferase reporters (Fig. 1b). (plasignaling.com)
c Abl activation attributable to mutant SOD1 in NSC 34 cells We then investigated no matter whether overexpression of mutant SOD1s influenced the expression of c Abl. (hormonespathway.com)
Western blot assessment revealed that the expression of c Abl was better in cells expressing mutant SOD1s than cells expressing wild variety SOD1. (hormonespathway.com)
Subcutaneous and orthotopic xenotransplantations by ectopic implantation of the human hormone-refractory PC-3M-luc cells were used to confirm in vivo anticancer effects of Lycorine. (oncotarget.com)
So as to determine if re expression of BRG1 in SK MEL5 cells resulted in elevated secretion of lively MMP2 and MMP9, we carried out gelatin zymography on supernatants derived from control and BRG1 expres sing SK MEL5 cells. (histaminereceptor-signal.com)
To determine the general biological conse quence of BRG1 re expression in SK MEL5 cells, we investigated if BRG1 promotes alterations in the ability of melanoma cells for being invasive in vitro. (histaminereceptor-signal.com)
To find out if loss of BRG1 compromises invasive skill in one of these extremely invasive cell lines, we down regulated BRG1 expression in WM 266 4 cells using a pool of siRNAs that target BRG1 but not the different ATPase, BRM. (histaminereceptor-signal.com)
Interestingly, BRM expression was slightly reduce in cells transfected with manage siRNA compared to untreated but then elevated in BRG1 down regulated cells. (histaminereceptor-signal.com)
We discovered that in WM 266 4 cells, BRM expression but not BRG1 or INI1 expression is sensitive to adjustments in WM 266 2 confluency. (histaminereceptor-signal.com)
Expression of Eomes in these cells correlates with high expression of CD122, the common beta-chain of the IL-2R and IL-15R. (thermofisher.com)
Consequently, ROS-modulation has emerged as an anticancer strategy with synthesis of various ROS-inducing or responsive agents that target cancer cells. (degruyter.com)
Our data demonstrate that beryllium-stimulated bronchoalveolar lavage cells produce IL-10, and the neutralization of endogenous IL-10 does not increase significantly cytokine production, HLA expression, or T lymphocyte pro- liferation. (cdc.gov)

Also the expression of the proinflammatory factors iNOS, IL-1 β , and TNF- α in the kidney and prefrontal cortex of brain in mice was suppressed by the oral administration of Rhodiola rosea crude extract (500 mg/kg). (hindawi.com)
The antitumor activity and survival analysis of VALD-3 in vivo was determined by the nude mice xenograft assay. (researchsquare.com)
Lycorine inhibited both growth and metastasis in multiple organs (liver, lung, kidney, spleen and bone) in vivo and improved mice survival. (oncotarget.com)

Pathological assessment of CCl4‑induced fibrotic livers revealed a significant reduction of liver injury and development of hepatic fibrosis in rats treated with APE (2.6 and 5.2 g/kg). (spandidos-publications.com)
These results suggested that APE may protect against liver damage and inhibit the progression of CCl4‑induced hepatic fibrosis. (spandidos-publications.com)

Here we investigated the effects of a synthetic killer peptide (KP), known to be active in vitro, ex vivo and/or in vivo against different pathogens, on C. albicans biofilm. (unipi.it)

Axin has been reported to be the concentration-limiting factor in regulatingtheefficiencyofthe b-catenindestructioncomplex7,8 andover- expression of axin induces b-catenin degradation in cell lines expressing truncated APC9-11. (plasignaling.com)
Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. (spandidos-publications.com)

Three A. fumigatus patient isolates (P-1, P-2, and P-3) were available for confirmatory species verification, reference susceptibility testing defined by the European Committee on Antimicrobial Susceptibility Testing using protocol for molds (E.Def 9.3), cyp51A Sanger sequencing (using wild-type reference sequence AF338659), and genotyping using the short tandem-repeat Aspergillus fumigatus (STR Af ) assay ( 2 , 3 ) ( Table ). (cdc.gov)

Overexpression of macrophage migration inhibitory factor (MIF) was identified in human GBM specimens that were MGMT methylated but showed poor survival. (nature.com)

The observed raise in MMP2 and MMP9 activity too as other alterations in extracellular matrix and adhesion molecule expression suggested that BRG1 plays a crucial purpose in regulating melanoma inva siveness. (histaminereceptor-signal.com)
Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. (cancerindex.org)

Comparable inhibitory effects were observed in all the strains employed, irrespective of their resistance or susceptibility to fluconazole. (unipi.it)

Echocardiographic parameters, myocardial fibrosis, NOX2 expression and EndMT were assessed. (dovepress.com)
TMZ may ameliorate EndMT and ISO-induced cardiac fibrosis through the NOX2/NF-κB/Snail pathway. (dovepress.com)
Liver fibrosis was induced in male Sprague‑Dawley rats by intraperitoneal injection of 50% CCl4 twice a week for eight weeks. (spandidos-publications.com)

There was also no translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus in apoptotic keratinocytes, indicating Tan IIA-induced apoptosis occurs mainly through the caspase pathway. (hindawi.com)
Ligation of integrin α2β1 on collagen prevents flow-induced NF-κB activation through a p38-dependent pathway that is activated locally at adhesion sites. (rupress.org)
In addition, CS and F3 significantly enhanced MA-10 cell StAR protein expression, which indicates that CS and F3 may use a cyclic adenosine monophosphate signal transduction pathway to activate MA-10 Leydig cell steroidogenesis in a manner to that of luteinizing hormone. (simpsonbiotech-usa.com)

PAX5, a transcription element necessary for B cell development, was strongly expressed in most SCLC situations and appeared to upregulate c Met transcription. (hormonespathway.com)
In hypoxia, several transcription factors are induced to respond to the decreased oxygen level. (spandidos-publications.com)

Finally, KP-mediated inhibitory effects were observed also against a catheter-associated C. albicans biofilm. (unipi.it)
Importantly, anti-cancer effects of Lycorine were dependent on STAT expression. (oncotarget.com)

Detection of MGMT promoter methylation correlates strongly with clinical response to TMZ and is also a positive prognostic biomarker in TMZ-treated GBM, including in elderly patients 8 , 9 . (nature.com)

Therefore, activation of MMP2 and probably MMP9 expres sion contributes on the BRG1 induced grow in SK MEL5 invasive potential. (histaminereceptor-signal.com)

These results strongly support the use of this folk medicine for liver cancer and HCV infection which is a global problem. (simpsonbiotech-usa.com)

The L-glutamate-induced neurotoxicity was suppressed by the treatment with rosin but not by rosarin. (hindawi.com)
Compared with the control group, the expression of NOX2, nuclear factor-κB (NF-κB), and Snail was increased in vivo and in vitro but decreased with TMZ treatment. (dovepress.com)
Our results clearly show that the treatment with KP strongly affected the capacity of C. albicans to form biofilm and significantly impairs preformed mature biofilm. (unipi.it)

By using a well established neuropathic pain animal model (partial ligation of the sciatic nerve), we demonstrated that intrathecal infusion of recombinant TGF-β1 significantly attenuated nerve injury-induced neuropathic pain. (biomedcentral.com)

We found that on top of that to MMPs, BRG1 also activated expression of TIMP2 and TIMP3, which might be anticipated to down modulate MMP activity. (histaminereceptor-signal.com)
In the present study, the maleic and succinic acid constituents (antrodins A-E) of this medicinal fungus, the in vivo metabolites of antrodin C and the analogue of one of the metabolites were tested for their inhibitory activity on HCV protease. (simpsonbiotech-usa.com)

Animals, surgical procedures, and in vivo treatments. (jneurosci.org)

We report a fatal aspergillosis case in which STR Af typing and whole-genome sequencing substantiated in vivo emergence of an azole-resistant Aspergillus fumigatus with a 120-bp tandem repeat in the promoter region of cyp51A . (cdc.gov)

Apoptosis and cell2

Vitro and in vivo3

Receptors2

Proliferation9

Oxidative stress1

Phosphorylation6

Gene expression4

Derived xenograft1

Inhibits2

Tumor4

Proteins6

Ferroptosis4

Cytotoxic2

Potent3

Accumulation2

Mutations3

Genes3

Antigen1

Outcomes1

Inflammatory3

Mechanisms1

Differentiation2

Downstream1

Hepatoprotective3

Inhibition4

Cells18

Mice3

Hepatic2

Pathogens1

Degradation2

Assay1

Overexpression1

Adhesion molecule expression2

Resistance1

Fibrosis3

Pathway3

Transcription2

Effects2

Correlates1

Activation1

Liver1

Treatment3

Ligation1

Activity2

Surgical1

Promoter1