scholarly journals A Novel Uromodulin Mutation C112Y Causing Familial Juvenile Hyperuricemic Nephropathy (FJHN) : Hsp70 Rescued the Cellular Apoptosis due to Its Protein Instability

2013 ◽  
Vol 37 (1) ◽  
pp. 43
Author(s):  
Sulistiyati Bayu Utami ◽  
Peili Li ◽  
Nobuhito Ikeda ◽  
Udin Bahrudin ◽  
Chishio Munemura ◽  
...  
Keyword(s):  
Cellular Apoptosis ◽  
Protein Instability ◽  
Familial Juvenile Hyperuricemic Nephropathy

scholarly journals Albendazole Exhibits Anti-Neoplastic Actions against Gastric Cancer Cells by Affecting STAT3 and STAT5 Activation by Pleiotropic Mechanism(s)

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 362
Author(s):  
Min Hee Yang ◽  
In Jin Ha ◽  
Jae-Young Um ◽  
Kwang Seok Ahn
Keyword(s):  
Gastric Cancer ◽  
Reactive Oxygen Species ◽  
Transcription Factors ◽  
Cancer Cells ◽  
Small Interfering Rna ◽  
Oxygen Species ◽  
Gastric Cancer Cells ◽  
Drug Induced ◽  
Cellular Apoptosis ◽  
Interfering Rna

Albendazole (ABZ) has been reported to display anti-tumoral actions against various maliganncies, but possible impact of ABZ on gastric cancer has not been deciphered. As aberrant phosphorylation of STAT3 and STAT5 proteins can regulate the growth and progression of gastric cancer, we postulated that ABZ may interrupt the activation of these oncogenic transcription factors. We found that ABZ exposure abrogated STAT3/5 activation, inhibited phosphorylation of Janus-activated kinases 1/2 and Src and enhanced the levels of SHP-1 protein. Silencing of SHP-1 gene by small interfering RNA (siRNA) reversed the ABZ-promoted attenuation of STAT3 as well as STAT5 activation and cellular apoptosis. In addition, these effects were noted to be driven by an augmented levels of reactive oxygen species caused by drug-induced GSH/GSSG imbalance. Thus, the data indicates that ABZ can modulate the activation of STAT3 and STAT5 by pleiotropic mechanisms in gastric cancer cells.

scholarly journals Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Renjie Dou ◽  
Jinjun Qian ◽  
Wei Wu ◽  
Yanxin Zhang ◽  
Yuxia Yuan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Type I ◽  
Disease Course ◽  
Mtor Signaling Pathway ◽  
Hairpin Rna ◽  
Aberrant Expression ◽  
Transcriptomic Sequencing ◽  
Family Protein ◽  
Cellular Apoptosis ◽  
Autophagic Process

AbstractSteroid 5α-reductase type I (SRD5A1) is a validated oncogene in many sex hormone-related cancers, but its role in multiple myeloma (MM) remains unknown. Based on gene expression profiling (GEP) of sequential MM samples during the disease course, we found that the aberrant expression of SRD5A1 was correlated with progression and poor prognosis in MM patients. In this study, the oncogenic roles of SRD5A1 were validated in human MM cell lines (ARP1 and H929) and the xenograft MM model as well as the 5TMM mouse model. MTT and flow cytometry were used to assess MM cell proliferation, cell cycle, and apoptosis post inducible knockdown SRD5A1 by lentivirus-mediated short-hairpin RNA (shRNA). Transcriptomic sequencing, immunofluorescence, and western blot were used to investigate the effects of SRD5A1 suppression on cell apoptosis and autophagy. Mechanistically, SRD5A1 downregulation simultaneously regulated both the Bcl-2 family protein-mediated apoptosis and the autophagic process via PI3K/Akt/mTOR signaling pathway in MM cells. Meanwhile, the autophagy inhibitor (3-methyladenine) and SRD5A1 inhibitor (Dutasteride) were utilized to evaluate their anti-myeloma effect. Thus, our results demonstrated that SRD5A1 downregulation simultaneously regulated both the apoptosis and the autophagic process in MM cells. The dual autophagy–apoptosis regulatory SRD5A1 may serve as a biomarker and potential target for MM progression and prognosis.

scholarly journals Regulation of Eosinophilia in Asthma—New Therapeutic Approaches for Asthma Treatment

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 817
Author(s):  
Ruth P. Cusack ◽  
Christiane E. Whetstone ◽  
Yanqing Xie ◽  
Maral Ranjbar ◽  
Gail M. Gauvreau
Keyword(s):  
Drug Targets ◽  
Airflow Obstruction ◽  
Chronic Inflammatory Disease ◽  
Therapeutic Approaches ◽  
Eosinophilic Asthma ◽  
Airway Eosinophilia ◽  
Gm Csf ◽  
New Therapeutic Approaches ◽  
Cellular Apoptosis ◽  
Reversible Airflow Obstruction

Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis. Blockade of the IL-5 pathway has been shown to be efficacious for the treatment of eosinophilic asthma. However, several other inflammatory pathways have been shown to support eosinophilia, including IL-13, the alarmin cytokines TSLP and IL-33, and the IL-3/5/GM-CSF axis. These and other alternate pathways leading to airway eosinophilia will be described, and the efficacy of therapeutics that have been developed to block these pathways will be evaluated.

The combined assessment of cellular apoptosis, mitochondrial function and proliferative response to pokeweed mitogen has prognostic value in SIV infection

1993 ◽  
Vol 22 (2-3) ◽  
pp. 147-153
Author(s):  
Ana M. Llano ◽  
Juan P. Amieiro‐Puig ◽  
Edmundo N. Kraiselburd ◽  
Matthew J. Kessler ◽  
Carlos A. Málaga ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Proliferative Response ◽  
Prognostic Value ◽  
Pokeweed Mitogen ◽  
Siv Infection ◽  
Cellular Apoptosis

scholarly journals Icaritin promotes apoptosis and inhibits proliferation by down-regulating AFP gene expression in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hui Li ◽  
Yujuan Liu ◽  
Wei Jiang ◽  
Junhui Xue ◽  
Yuning Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cellular Proliferation ◽  
Chinese Herb ◽  
New Drugs ◽  
Phase Iii ◽  
P53 Expression ◽  
Expression Levels ◽  
Cellular Apoptosis ◽  
Afp Promoter

Abstract Background Icaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway. Methods Real-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting. Results Our results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis. Conclusion Our findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.

scholarly journals Effect of Pre-Fermentative Maceration and Fining Agents on Protein Stability, Macromolecular, and Phenolic Composition of Albariño White Wines: Comparative Efficiency of Chitosan, k-Carrageenan and Bentonite as Heat Stabilisers

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 608
Author(s):  
Inma Arenas ◽  
Miguel Ribeiro ◽  
Luís Filipe-Ribeiro ◽  
Rafael Vilamarim ◽  
Elisa Costa ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Protein Stability ◽  
White Wine ◽  
The Other ◽  
White Wines ◽  
Comparative Efficiency ◽  
Fining Agents ◽  
Protein Instability ◽  
Related Proteins ◽  
Protein Stabilisation

In this work, the effect of pre-fermentative skin maceration (PFSM) on the chemical composition of the macromolecular fraction, polysaccharides and proteins, phenolic compounds, chromatic characteristics, and protein stability of Albariño monovarietal white wines was studied. PFSM increased the extraction of phenolic compounds and polysaccharides and reduced the extraction of pathogenesis-related proteins (PRPs). PFSM wine showed significantly higher protein instability. Sodium and calcium bentonites were used for protein stabilisation of wines obtained with PFSM (+PFSM) and without PFSM (−PFSM), and their efficiencies compared to fungal chitosan (FCH) and k-carrageenan. k-Carrageenan reduced the content of PRPs and the protein instability in both wines, and it was more efficient than sodium and calcium bentonites. FCH was unable to heat stabilise both wines, and PRPs levels remained unaltered. On the other hand, FCH decreased the levels of wine polysaccharides by 60%. Sodium and calcium bentonite also decreased the levels of wine polysaccharides although to a lower extent (16% to 59%). k-Carrageenan did not affect the wine polysaccharide levels. Overall, k-carrageenan is suitable for white wine protein stabilisation, having a more desirable impact on the wine macromolecular fraction than the other fining agents, reducing the levels of the wine PRPs without impacting polysaccharide composition.

The in vitro evaluation of antibacterial efficacy optimized with cellular apoptosis on multi-functional polyurethane sealers for the root canal treatment

2021 ◽  
Vol 9 (5) ◽  
pp. 1370-1383
Author(s):  
Xiaoyu Lei ◽  
Jian Wang ◽  
Jie Chen ◽  
Jing Gao ◽  
Jinzheng Zhang ◽  
...  
Keyword(s):  
Root Canal ◽  
Evaluation System ◽  
Root Canal Treatment ◽  
Antibacterial Efficacy ◽  
Apoptotic Pathway ◽  
In Vitro Evaluation ◽  
Cellular Apoptosis ◽  
Genetic Assessment

Combined with a series of antibacterial tests and the genetic assessment of the apoptotic pathway, an evaluation system has been rationalized to govern the fate of the different compositions of PU-based sealers.

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