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#33652354   2021/02/23 To Up

Discovery of A031 as effective proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader for the treatment of prostate cancer.

Androgen receptor (AR) is an effective therapeutic target for the treatment of prostate cancer. We report herein the design, synthesis, and biological evaluation of highly effective proteolysis targeting chimeras (PROTAC) androgen receptor (AR) degraders, such as compound A031. It could induce the degradation of AR protein in VCaP cell lines in a time-dependent manner, achieving the IC 50 value of less than 0.25 μM. The A031 is 5 times less toxic than EZLA and works with an appropriate half-life (t 1/2) or clearance rate (Cl). Also, it has a significant inhibitory effect on tumor growth in zebrafish transplanted with human prostate cancer (VCaP). Therefore, A031 provides a further idea of developing novel drugs for prostate cancer.
Linrong Chen, Liuquan Han, Shujun Mao, Ping Xu, Xinxin Xu, Ruibo Zhao, Zhihua Wu, Kai Zhong, Guangliang Yu, Xiaolei Wang

1618 related Products with: Discovery of A031 as effective proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader for the treatment of prostate cancer.

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#33647481   2021/02/26 To Up

High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells.

Clear cell renal cell carcinoma (ccRCC) is a frequently occurring renal cancer. Von Hippel-Lindau disease tumor suppressor (VHL), a known tumor suppressor, is frequently mutated in about 50% of patients with ccRCC. However, it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL. In the present study, we found that higher expression of VHL was correlated with the better disease-free survival (DFS) in ccRCC patients using The Cancer Genome Atlas (TCGA) datasets. We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition (EMT), sterol regulatory element-binding protein 1 (SREBP1) regulated triglyceride synthesis, and cell proliferation. Proteomic analysis provided us a global view that VHL regulated four biological processes including metabolism, immune regulation, apoptosis, and cell movement. Importantly, we found that VHL overexpression led to upregulation of proteins associated with antigen processing and interferon-responsive proteins, rendering ccRCC cells with high VHL expression more sensitive to interferon treatment. We defined an interferon-responsive signature (IRS) with ten proteins, whose expression levels were positively correlated with DFS in ccRCC patients. Taken together, our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy.
Songbiao Zhu, Wenxi Ding, Yuling Chen, Weixuan Wang, Renhua Xu, Chongdong Liu, Xiaohui Liu, Haiteng Deng

2672 related Products with: High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells.

4 Membranes/Box4 Arrays/Slide1.00 flask96 tests100 µg

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#33643814   2020/09/19 To Up

Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.

Cullin-RING ligases (CRLs) recognize and interact with substrates for ubiquitination and degradation, and can be targeted for disease treatment when the abnormal expression of substrates involves pathologic processes. Phosphorylation, either of substrates or receptors of CRLs, can alter their interaction. Phosphorylation-dependent ubiquitination and proteasome degradation influence various cellular processes and can contribute to the occurrence of various diseases, most often tumorigenesis. These processes have the potential to be used for tumor intervention through the regulation of the activities of related kinases, along with the regulation of the stability of specific oncoproteins and tumor suppressors. This review describes the mechanisms and biological functions of crosstalk between phosphorylation and ubiquitination, and most importantly its influence on tumorigenesis, to provide new directions and strategies for tumor therapy.
Yifan Chen, Xuejing Shao, Ji Cao, Hong Zhu, Bo Yang, Qiaojun He, Meidan Ying

2631 related Products with: Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.

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#33643089   2021/02/10 To Up

The Impacts of SARS-CoV-2 Pandemic on Suicide: A Lexical Analysis.

Although COVID-19 is a public health emergency, its consequences for the mental health of the population are still scarce. Likewise, its impact on critical situations such as suicide is still poorly explored in the literature. Therefore, this study aimed to analyze in a pioneering way, through lexical and content analysis techniques, the possible impacts of the new COVID-19 pandemic on suicide behavior. A lexical analysis, whose sample (not probabilistic, i.e., for convenience) was made up of full-length papers (abstracts) and short communications, about suicide behavior in COVID-19 pandemic, in PubMed and Virtual Health Library (VHL) was carried out following a lexical and content analysis using the software IRaMuTeQ, version 0.7 alpha 2. The most frequent active words were suicide behavior ( = 649), covid ( = 439), health ( = 358), mental ( = 268), and social ( = 220). Four lexical classes were found and organized into two large groups: the first group, formed by the classes 2 ("methods for psychological treatment") and 3 ("strategies to minimize the COVID-19 impacts"), was the most representative, totaling 50.6% of the text segments and second group formed by classes 1 ("signs of clinical depression") and 4 ("COVID-19 pandemic as a public health problem") with 49.4% of the text segments. Facing suicide behavior, the direct effects of the COVID-19 pandemic, and the negative feelings and trigger of previous psychiatric illnesses; the measures to deal with the pandemic such as social isolation, decrease in the number of professionals, the opening hours of health establishments, and decrease in the demand for medications; and competing phenomena such as the spread of fake news and lack of empathy are aggressive and potentiating factors of suicidal ideation.
Jucier Gonçalves Júnior, Jair Paulino de Sales, Marcial Moreira Moreno, Modesto Leite Rolim-Neto

1818 related Products with: The Impacts of SARS-CoV-2 Pandemic on Suicide: A Lexical Analysis.

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#33641653   2021/02/25 To Up

Arsenic Dispensing Powder Promotes Erythropoiesis in Myelodysplastic Syndromes via Downregulation of HIF1A and Upregulation of GATA Factors.

Traditional Chinese Medicine (TCM) is a practical medicine based on thousands of years of medical practice in China. Arsenic dispensing powder (ADP) has been used as a treatment for MDS patients with a superior efficacy on anemia at Xiyuan Hospital of China Academy of Chinese Medical Sciences. In this study, we retrospectively analyzed MDS patients that received ADP treatment in the past 9 years and confirmed that ADP improves patients' anemia and prolongs overall survival in intermediate-risk MDS patients. Then, we used the MDS transgenic mice model and cell line to explore the drug mechanism. In normal and MDS cells, ADP does not show cellular toxicity but promotes differentiation. In mouse MDS models, we observed that ADP showed significant efficacy on promoting erythropoiesis. In the BFU-E and CFU-E assays, ADP could promote erythropoiesis not only in normal clones but also in MDS clones. Mechanistically, we found that ADP could downregulate HIF1A in MDS clones through upregulation of VHL, P53 and MDM2, which is involved in two parallel pathways to downregulate HIF1A. We also confirmed that ADP upregulates GATA factors in normal clones. Thus, our clinical and experimental studies indicate that ADP is a promising drug to promote erythropoiesis in both MDS and normal clones with a superior outcome than current regular therapies. ADP promotes erythropoiesis in myelodysplastic syndromes via downregulation of HIF1A and upregulation of GATA factors.
Teng Fan, Xiaomin Feng, Asumi Yokota, Weiyi Liu, Yuting Tang, Xiaomei Yan, Haiyan Xiao, Yue Wang, Zhongyang Deng, Pan Zhao, Mingjing Wang, Hongzhi Wang, Rou Ma, Xiaomei Hu, Gang Huang

2924 related Products with: Arsenic Dispensing Powder Promotes Erythropoiesis in Myelodysplastic Syndromes via Downregulation of HIF1A and Upregulation of GATA Factors.

100 μg1 Set 5 G100 μg100mg100 units100mg100 ug/vial20 µl (10 mM)

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#33627071   2021/02/24 To Up

Effectiveness of community and school-based sanitation interventions in improving latrine coverage: a systematic review and meta-analysis of randomized controlled interventions.

Approximately 1000 children die each year due to preventable water and sanitation-related diarrheal diseases. Six in 10 people lacked access to safely managed sanitation facilities in 2015. Numerous community- and school-based approaches have been implemented to eradicate open defecation practices, promote latrine ownership, improve situation sanitation, and reduce waterborne disease.
Satoshi Igaki, Nguyen Tran Minh Duc, Nguyen Hai Nam, Tran Thi Tuyet Nga, Parshal Bhandari, Amr Elhamamsy, Caroline Ibrahim Lotify, Mostafa Elsayed Hewalla, Gehad Mohamed Tawfik, Peterson Gitonga Mathenge, Masahiro Hashizume, Nguyen Tien Huy

2942 related Products with: Effectiveness of community and school-based sanitation interventions in improving latrine coverage: a systematic review and meta-analysis of randomized controlled interventions.

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#33616026   2021/02/22 To Up

Update on SARS-CoV-2 infection in children.

Despite the worldwide spread of SARS-CoV-2 infection (COVID-19), knowledge of the different clinical presentations, ways of transmission, severity and prognosis in children and adolescents is limited. An increasing number of reports describe some of these characteristics in this age range. A non-systematic review was undertaken using MEDLINE (PubMed), LILACS (VHL), Scopus, Web of Science, Cochrane and CAPES Portal databases from 1 January until 30 September 2020 [103] with the search terms SARS-CoV-2, COVID-19, child, children, youth, adolescent and newborn to identify the more recent clinical aspects of SARS-CoV-2 infection in children. In general, SARS-CoV-2 infection in children tends to be asymptomatic or to have mild or moderate signs, and most young ones are infected by family members. Recent reports offer new insights into the disease. Current evidence on SARS-CoV-2 infection in children and adolescents is presented, especially concerning the clinical presentation, imaging and uncommon severe forms of the disease, particularly the COVID-19-associated multisystem inflammatory syndrome. The impact of COVID-19 infection in the perinatal period is described in detail. Knowledge of the various clinical presentations of SARS-CoV-2 in children and adolescents allows the paediatrician to diagnose earlier, monitor warnings signs, implement treatment and, especially, establish preventive measures. : ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; ARF, acute rheumatic fever; CAA, coronary artery aneurysms; CK-MB, creatine kinase-MB; COVID-19, coronavirus disease-2019; HLA, specific human leucocyte antigen; IPC, infection prevention and control; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; MIS-C, COVID-19-associated multisystem inflammatory syndrome; RNA, ribonucleic acid; RT-PCR, reserve transcription-polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; TCT, thoracic computed tomography; TSS, toxic shock syndrome; WHO, World Health Organization.
Marlos Melo Martins, Arnaldo Prata-Barbosa, Antônio José Ledo Alves da Cunha

1129 related Products with: Update on SARS-CoV-2 infection in children.

96 tests 500 G2000 Units20mg5mg1200ul 5 G25ml2000 pcs

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#33602720   2021/02/18 To Up

Modified Hypoxia-Inducible Factor Expression in CD8+ T Cells Increases Antitumor Efficacy.

Adoptive transfer of antitumor cytotoxic T cells is an emerging form of cancer immunotherapy. A key challenge to expanding the utility of adoptive-cell therapies is how to enhance the survival and function of the transferred T cells. Immune-cell survival requires adaptation to different microenvironments, and particularly to the hypoxic milieu of solid tumors. The hypoxia-inducible factor (HIF) transcription factors are an essential aspect of this adaptation. In this study, we undertook experiments to define structural determinants of HIF that potentiate antitumor efficacy in cytotoxic T cells. We first created retroviral vectors to deliver ectopic expression of HIF1ɑ and HIF2ɑ in mouse CD8+ T cells, together or individually, and with or without sensitivity to the oxygen-dependent HIFɑ inhibitors Von Hippel-Lindau (VHL) and Factor Inhibiting HIF (FIH). HIF2ɑ, but not HIF1ɑ, drove broad transcriptional changes in CD8+ T cells, resulting in increased cytotoxic differentiation and cytolytic function against tumor targets. A specific mutation replacing the hydroxyl group-acceptor site for FIH in HIF2ɑ gave rise to the most effective antitumor T cells after adoptive transfer in vivo. In addition, co-delivering an FIH-insensitive form of HIF2ɑ with an anti-CD19 chimeric antigen receptor greatly enhanced cytolytic function of human CD8+ T cells against lymphoma cells both in vitro and in a xenograft adoptive transfer model. These experiments point to a means to increase the antitumor efficacy of therapeutic CD8+ T cells via ectopic expression of the HIF transcription factor.
Pedro Veliça, Pedro P Cunha, Nikola Vojnovic, Iosifina Petrina Foskolou, David Bargiela, Milos Gojkovic, Helene Rundqvist, Randall S Johnson

1578 related Products with: Modified Hypoxia-Inducible Factor Expression in CD8+ T Cells Increases Antitumor Efficacy.

0.1 mg96T100 μg0.1ml (1mg/ml)100 ug10 ug0.1 mg100 ug96 tests1 mg

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