Search PubMedSearch

Biomedical subjects

Yu Hou

Publications and source records attributed to Yu Hou.

4 recordsLinked to original sources

Mov10 mitigates hematopoietic stem cell exhaustion under stress by modulating the Camp-mediated inflammatory pathway.

The integrity of hematopoietic stem cell (HSC) function is crucial for robust hematopoietic regeneration following stress. Inflammatory responses are pivotal drivers of HSC stress response, yet the precise modulation of inflammatory pathways remains incompletely defined. In this study, we identify the RNA helicase Mov10 as a negative regulator of stress-induced inflammatory pathways in HSC. Our study indicates that Mov10, which is critically required for HSC maintenance, is highly expressed in HSC, and its loss adversely affects HSC fitness and survival during hematopoietic stress induced by bone marrow transplantation and irradiation (IR). Mechanistically, Mov10 mitigates excessive inflammatory activation to sustain HSC functional integrity during hematopoietic stress, primarily by enhancing the translation of CAMP, which inhibits the interaction between TNF-α and its receptor TNFR1 and suppresses NF-κB activation. Overall, our results imply that Mov10 plays a critical role in averting functional failure of hematopoiesis under stress, presenting viable paths for the therapeutic intervention of relevant diseases.

Camp

Selective Extraction of Genomic DNA From Animal Tissues Using a Hydrophobic Magnetic Ionic Liquid.

The development of green and efficient methods for genomic DNA extraction from animal tissues is crucial for molecular diagnostics, food traceability, and genetic research. Conventional methods often involve toxic reagents, multiple centrifugation steps, and are time-consuming. In this study, a hydrophobic magnetic ionic liquid (MIL), N-octyl-4-dimethylaminopyridinium hexafluorophosphate MIL ([C8DMAP][PF6]‑Ni MIL), was synthesized and applied for the selective extraction of genomic DNA from various animal tissues. The material exhibited strong paramagnetic behavior, high thermal stability, and excellent hydrophobicity, enabling rapid phase separation under an external magnetic field. A mechanical shaking-assisted extraction method was developed, and key parameters including temperature, time, shaking speed, and [C8DMAP][PF6]-Ni MIL dosage were systematically optimized. The method demonstrated high selectivity for DNA over proteins, RNA, and amino acids, with a maximum recovery rate of 78.06 ± 1.91%. Compared to a commercial DNA extraction kit, the [C8DMAP][PF6]-Ni MIL-based approach provided higher yields from several tissues, including mouse liver, brain, and rabbit lung. Furthermore, the [C8DMAP][PF6]-Ni MIL could be reused for at least six cycles while maintaining extraction efficiency. This work not only provides a high-performance material for DNA extraction, but also demonstrates a sustainable and easily retrievable liquid-phase separation strategy, offering a generalizable platform for complex sample pretreatment.

Animals

Predicting Weight Loss After Vertical Sleeve Gastrectomy Using a Whole-genome Sequencing-derived Polygenic Risk Score in the All of Us Cohort.

OBJECTIVE: To create a genome-wide polygenic risk score (PRS) to improve prediction of a 12-month percentage weight loss (WL) after vertical sleeve gastrectomy (VSG). BACKGROUND: Variability in post-VSG WL is not well explained by clinical factors. The All of Us program provides access to a 414,830 short-read whole-genome sequencing resource, enabling unbiased discovery of genetic predictors after VSG. METHODS: VSG counts, demographic, anthropomorphic and vital sign information were obtained from the linked electronic health record. The discovery cohort (DC) included participants from version 7 carried into version 8 while the validation cohort (VC) included those newly added to v8. We defined good responders and nonresponders as having WL&#xb1;1SD from the mean. Following quality filtering, we applied a 2-stage penalized-regression, followed by elastic-net logistic regression, to identify 1583 stable variants and derive &#x3b2;-weights. We then tested this PRS on the DC into a prediction model. RESULTS: We identified 395 participants in the DC and 336 participants in the VC, respectively. Of these, VSG, 44 were classified as good responders (&#x2265;37% WL) and 55 as nonresponders (&#x2264;19% WL). In the VC, 55 were classified as good responders and 48 as nonresponders. Adding the PRS to models to clinical predictors increased the area under the curve following logistic regression by 0.03; P <4.3 &#xd7; 10 -14 , random forest by 0.03; P <9.1 &#xd7; 10 -7 , decision tree by 0.05; P = 1.2 &#xd7; 10 -3 , and gradient boosting by 0.08; P <8.3 &#xd7; 10 -10 . CONCLUSIONS: Use of short-read whole-genome sequencing from All of Us (AoU) can be effectively used to generate PRS to enhance predictive WL accuracy. This work has implications for outcomes of both bariatric surgery and other surgical procedures.

Humans

Integrated ubiquitomics characterization of hepatocellular carcinomas.

BACKGROUND AND AIMS: Patients with aggressive HCC have limited therapeutic options. Therefore, a better understanding of HCC pathogenesis is needed to improve treatment. Genomic studies of HCC have improved our understanding of cancer biology. However, the ubiquitomic characteristics of HCC remain poorly understood. We aimed to reveal the ubiquitomic characteristics of HCC and provide clinical feature biomarkers of the aggressive HCC that may be used for diagnosis or therapy in the clinic. APPROACH AND RESULTS: The comprehensive proteomic, phosphoproteomic, and ubiquitomic analyses were performed on tumors and adjacent normal liver tissues from 85 patients with HCC. HCCs displayed overexpression of drugable targets CBR1-S151 and CPNE1-S55. COL4A1, LAMC1, and LAMA4 were highly expressed in the disease free survival-poor patients. Phosphoproteomic and ubiquitomic features of HCC revealed cross talk in metabolism and metastasis. Ubiquitomics predicted diverse prognosis and clarified HCC subtype-specific proteomic signatures. Expression of biomarkers TUBA1A, BHMT2, BHMT, and ACY1 exhibited differential ubiquitination levels and displayed high prognostic risk scores, suggesting that targeting these proteins or their modified forms may be beneficial for future clinical treatment. We validated that TUBA1A K370 deubiquitination drove severe HCC and labeled an aggressive subtype of HCCs. TUBA1A K370 deubiquitination was at least partly attributed to protein kinase B-mediated USP14 activation in HCC. Notably, targeting AKT-USP14-TUBA1A complex promoted TUBA1A degradation and blocked liver tumorigenesis in vivo. CONCLUSIONS: This study expands our knowledge of ubiquitomic signatures, biomarkers, and potential therapeutic targets in HCC.

Humans