Jingjing Li, Shanghai Institute of Nutrition and Health, CAS,2023.12.27

Description

Pancreatic progenitor cell differentiation and proliferation factor (PPDPF) has been reported to play a role in tumorigenesis. However, its function in hepatocellular carcinoma (HCC) remains poorly understood. In this study, we report that PPDPF is significantly downregulated in HCC and indicats poor prognosis and survival for HCC patients. In the DEN-induced HCC mouse model, hepatocyte-specific depletion of Ppdpf promots hepatocarcinogenesis, and reintroduction of PPDPF into LKO mice inhibits the accelerated HCC development. Mechanistic study reveals that PPDPF regulated NF-kB signaling through modulation of RIPK1 ubiquitination. PPDPF interacts with RIPK1 and facilitates K63-linked ubiquitination of RIPK1 via recruiting the E3 ligase TRIM21, which catalyzs K63-linked ubiquitination of RIPK1 on K140. In addition, liver-specific overexpression of PPDPF activats NF-kB signaling, attenuats apoptosis and compensatory proliferation in mice, which significantly suppresses HCC development. This work identifies PPDPF as a regulator of NF-kB signaling and provides a potential therapeutic candidate for HCC.

OEP004906

Yu Sun, Shanghai Institute of Nutrition and Health, CAS,2023.12.27

Description

Aging and age-related pathologies can be delayed by specifically targeting the senescence-associated secretory phenotype (SASP), a hallmark feature of senescent cells. Achieving the goal using natural or synthetic agents would have a tremendous impact on the quality of lifespan and burden of age-related chronic diseases. We report the potential of rutin, a bioactive phytochemical component derived from natural plants specifically ginkgo boliva, in targeting senescent cells via suppression of the SASP. This study demonstrates the efficacy of rutin as medicinal agent in controlling the influence of senescent human stromal cells and provides a strong rationale for its future use in aging intervention and geriatric medicine. Overall design: Examination of in vitro efficacy of rutin, a polyphenolic compound in treating human senescent stromal cells (PSC27 line). Ginkgo biloba products are widely consumed herbal supplements that contain ingredients with anti-oxidant potentials. However, the active agents in ginkgo biloba extracts (GBE) remain unclear, and its major ingredients such as rutin has not been extensively investigated in cellular senescence. This assay was performed beyond previous studies reporting the effects of GBE in anti-diabetic, anti-cataract therapy, anti-inflammation and anti-tumor therapies.

OEP004909

Wang lan, Shanghai Institute of Nutrition and Health,2023.12.11

Description

Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs. Mechanistically, UHRF1 directly interacts with Sin3A associated protein 30 (SAP30) through two amino acids, G572 and F573 in its SRA domain, to repress gene expression. Depletion of UHRF1 or SAP30 derepresses an important target gene, MXD4, which encodes a MYC antagonist, and leads to suppression of leukemogenesis. Knockdown of MXD4 can rescue the leukemogenesis by activating the MYC pathway. Lastly, we identified a UHRF1 inhibitor, UF146, and demonstrated its significant therapeutic efficacy in the myeloid leukemia PDX model. Taken together, these studies reveal the mechanisms for altered epigenetic programs in AML and provide a promising targeted therapeutic strategy against AML.

OEP004818

Jinxin Xu, Xiamen University,2023.03.12

Description

OEP004010

Lunshan Xu, Army Medical University Daping Hospital: Third Military Medical University Daping Hospital,2024.02.02

Description

Glioblastoma (GBM) is the most aggressive brain tumor type with worse clinical outcome, due to the hallmarks of strong invasiveness, high rate of recurrence and therapeutic resistance to temozolomide (TMZ), the first-line drug for GBM, representing a major challenge for successful GBM therapeutics. Understanding the underlying mechanisms that drive GBM progression will shed novel insight on therapeutic strategies. Receptor-type tyrosine-protein phosphatase S (PTPRS) is a frequently mutated gene in human cancers, including GBM. Its role in GBM has not yet clarified. Here, inactivating PTPRS mutation or deficiency were frequently found in GBM, and deficiency in PTPRS significantly induced defects in G2M checkpoint and limited GBM cells proliferation, leading to potent resistance to TMZ treatment in vitro and in vivo. Surprisingly, loss of PTPRS triggered an unexpected mesenchymal phenotype that markedly enhances migratory capabilities of GBM cells through upregulating numerous matrix metalloproteinases (MMPs) via MAPK-MEK-ERK signaling. Therefore, this work provides a therapeutic window for precisely excluding PTPRS-mutated patients that does not respond to TMZ.

OEP005053

Wang Zeqing, The Interdisciplinary Research Center on Biology and Chemistry,2022.07.07

Description

OEP003508

Yihua Sun, ,2020.03.22

Description

We addressed the microbial composition, community assembly, and nitrogen metabolism in the oxygen minimum zones (OMZs) in Yangtze Estuary water using 16S rRNA gene sequencing, modeling, and metagenomics analyses.

OEP000802

Xinxu Zhang, Shenzhen University,2022.12.08

Description

The sediment sample is collected from the Mariana Trench slope in the western Pacific Ocean at the water depth of 8300 mbsl.

OEP003780

Lei Zhang, Shandong University,2024.01.31

Description

We transplanted gut microbiota from human donors with ASD or typically developing (TD) controls into antibiotic-treated mice. We analysed DNA methylation of specific target genes of both parental and offspring mice.

OEP005039

Hongmei Wang, China university of geosciences,2023.12.01

Description

OEP004782