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Machine learning reveals UHRF-X as a biomarker for systemic lupus erythematosus and an antagonistic protein against UHRF1 E3 ligase
No full text[[abstract]]Inflammatory T cells contribute to the pathogenesis of the autoimmune diseases such as systemic lupus erythematosus (SLE). Analysis of the T-cell transcriptomics data of two independent SLE patient cohorts by three machine learning models revealed UHRF-X as a novel SLE biomarker. T-cell-specific UHRF-X transgenic mice manifested the induction of IL-17A and autoimmune inflammation. Mechanistically, UHRF-X prevented UHRF1-induced Lys48-linked ubiquitination and degradation of MAP4K3 (GLK), which is a kinase known to induce IL-17A. Consistently, IL-17A induction and autoimmune phenotypes of UHRF-X transgenic mice were obliterated by MAP4K3 knockout. Furthermore, UHRF-X protein was indeed overexpressed in peripheral blood T cells of SLE patients. Collectively, UHRF-X overexpression in T cells inhibits the E3 ligase function of UHRF1 and induces IL-17A-mediated autoimmune responses. This report unveils a novel gene that can block UHRF1 function, leading to autoimmune disease
Hepatitis and hepatitis B virus reactivation in everolimus-treated solid tumor patients: A focus on HBV-endemic areas
No full text[[abstract]]Background: Everolimus is approved for treating breast, renal, and pancreatic neuroendocrine cancers but carries the risk of hepatitis B virus (HBV) reactivation (HBVr) and hepatitis. However, data on HBVr in everolimus-treated patients are limited. This study evaluates the risk of hepatitis and HBVr in cancer patients with current or past HBV infection. Methods: This retrospective study analyzed patients prescribed everolimus between 1 January 2011 and 31 May 2022, using a private healthcare system database in Taiwan. Patients with HBsAg positivity or HBsAg negativity and anti-HBs or anti-HBc results were included. The cumulative incidence function and risk of hepatitis from a competing risk model, which estimates Fine-Gray subdistribution hazard (SDH), were analyzed across different HBV serological subgroups. The risk of hepatitis B reactivation was also calculated. Results: Of 377 patients, 45% (36/80) of HBsAg-positive and 0.67% (2/297) of HBsAg-negative patients received nucleos(t)ide analogues (NUCs) prophylaxis. Hepatitis occurred in 28.75% of HBsAg-positive and 17.85% of HBsAg-negative patients. Baseline HBsAg positivity and exemestane use increased hepatitis risk. HBVr occurred in 11.36% (5/44) of HBsAg-positive patients without NUCs and 5.56% (2/36) with prophylaxis. Two HBsAg-negative, anti-HBc-positive patients developed severe HBVr-related hepatitis. Conclusion: Hepatitis occurred in 28.75% of HBsAg-positive and 17.85% of HBsAg-negative patients on everolimus. HBVr was common in HBsAg-positive patients but rare in HBsAg-negative individuals. HBV screening and liver function monitoring are critical for patients with past or current HBV infection receiving everolimus, especially in endemic areas
Long-term exposure to multiple air pollutants and risk of Parkinson's disease: A population-based multipollutant model study
No full text[[abstract]]BACKGROUND: Recent evidence suggests brain-first Parkinson's disease (PD) may start from the olfactory system, indicating potential inhalational exposure to causal agents. We investigated the impact of long-term exposure to various air pollutants on PD incidence using both single- and multi-pollutant models to account for interactions between pollutants. METHODS: This retrospective population study used data from Taiwan's National Health Insurance Research Database (2006 and 2018) and included individuals aged 40-65 without PD. Personal exposure levels to various air pollutants, including PM(2.5), PM(10), NO(2), O(3), SO(2) and CO, were calculated using the hybrid Kriging/land-use regression method. Cox regression models were used to analyse the association between pollutants and PD incidence, adjusting for covariates. RESULTS: A total of 5 113 322 individuals without PD (mean age 50.1±6.9 years, 47.3% men) were followed for an average of 11.2±2.4 years, during which 20 694 incident cases of PD were identified. In the single-pollutant model, exposure to PM(2.5) (HR 2.65 (95% CI 2.59 to 2.72)), PM(10) (HR 3.13 (3.04 to 3.22)), NO(2) (HR 1.74 (1.68 to 1.80)) and SO(2) (HR 1.68 (1.65 to 1.71)) was associated with an increased risk of PD. These associations remained robust in the multipollutant model. A positive association between exposure to O(3) and an increased risk of PD (HR 1.29 (1.25-1.33)) was observed after adjusting for co-pollutants. CONCLUSIONS: This nationwide cohort study employing multiple-pollutant models for considering the interaction effects revealed an association between exposure to multiple air pollutants and the risk of PD, emphasising the need for early prevention strategies
Advancing precision therapy for colorectal cancer: Developing clinical indications for multi-target kinase inhibitor BPR1J481 using patient-derived xenograft models
No full text[[abstract]]The large and rapid increase in the incidence and mortality of colorectal cancer (CRC) demonstrates the urgent need for new drugs with higher efficacy to treat CRC. However, the lack of applicable and reliable preclinical models significantly hinders the progress of drug development. Patient-derived xenograft (PDX) models are currently considered reliable in vivo preclinical models for predicting drug efficacy in cancer patients. This study successfully uses the CRC PDX model to develop clinical indications for the new multi-target kinase inhibitor BPR1J481 and demonstrated the anti-cancer mechanism and competitive advantages of this drug candidate. The results demonstrate that BPR1J481 exhibits significant anticancer efficacy by inducing apoptosis in CRC PDX tumor tissues and corresponding PDX-derived CRC cells. Through kinase competitive binding and kinase activity assays, we discover that BPR1J481 effectively inhibits SRC kinase activity by directly binding to its active site. The reduction in SRC phosphorylation observed in CRC PDX tumor tissues and derived cells upon treatment with BPR1J481 further validates its inhibitory potential. Furthermore, the decrease in viable cells after SRC knockout and the poorer prognosis observed in patients with higher SRC expression, emphasizes the critical significance and clinical relevance of SRC in CRC. Additionally, BPR1J481 exhibits robust anti-angiogenic effects by suppressing VEGF- and PDGF-induced endothelial cell proliferation, migration, and capillary-like tube formation through inhibition of VEGFR2 and PDGFRβ phosphorylation. Remarkably, BPR1J481 appears to demonstrate greater efficacy against CRC compared to regorafenib. These findings highlight the therapeutic potential of BPR1J481 for patients with CRC
Aminothiazole compounds as protein kinase inhibitors
No full text[[abstract]]Aminothiazole compounds of Formula (I) shown below and pharmaceutical compositions containing one of such compounds. Also disclosed are methods of inhibiting a tyrosine kinase and treating cancer associated with a tyrosine kinase with one of the aminothiazole compounds
Aminothiazole compounds as protein kinase inhibitors
No full text[[abstract]]Aminothiazole compounds of Formula (I) shown below and pharmaceutical compositions containing one of such compounds. Also disclosed are methods of inhibiting a tyrosine kinase and treating cancer associated with a tyrosine kinase with one of the aminothiazole compounds
[[alternative]]Methods and kits of prognostically classifying and use of manufacturing pharmaceutical composition using nucleic acid for inhibiting cancer stem cell aggregation or tumor migration
No full text[[abstract]]本揭露包含分子標記的鑑定，包括ASPM、ATP9A、ACOX3、CDC45L、SLC40A1、AGR2、ATP11C、FAM72A、PLA2G10、MATN2、APITD1、KIF11、HPGD、HMMR、ELF3、PTTG1、UPP1、CCNB2、CREG1、ARSD、CENPN、SMC4、DLGAP5、PIK3AP1、TLR3、TWIST1、GCLM及CTSS，此與胰臟癌的分化和臨床預後相關。更特定地，本揭露包含基因標記組的鑑定，基因標記組的表現量可用來從具較低程度分化的胰臟癌細胞區別具較高程度分化的胰臟癌。這些標記可用於評估胰臟癌的臨床預後，包括宿主的疾病進展、復發或死亡。本揭露也提供治療腺體癌症的方法與用於測定腺體癌症的套組，像是胰臟癌、乳癌、和攝護腺癌，此係藉由抑制ASPM的表現或是抑制其活化或維持Wnt訊息活性之能力及/或腺體癌症的癌症幹細胞群集的能力
CPG寡脫氧核苷酸、包含其的免疫組合物及製備組合物並通過其刺激免疫反應的方法
No full text[[abstract]]在这里公开一种CpG寡脱氧核苷酸(CpG‑ ODN)，其是作为开发用于在不同物种中使用作为佐剂的有效免疫刺激。TLR9为CpG‑ODN的细胞受体，且目前开发的CpG‑ODN对兔子的TLR9具有低 活性。本文中，包含约11‑14个脱氧核苷酸的GACGTT或AACGTT基序的CpG‑ODN类型展现出对兔子的TLR9具有有效的免疫刺激活性，且能够在兔子中提升较少毒性且有效的抗体反应
γ-聚麸胺酸类眼科手术冲洗液
No full text[[abstract]]本发明公开了一种含量足以冲洗患者眼部组织的眼科手术冲洗液，其包括：a)增加该冲洗液黏度的有效量γ-聚麸胺酸(γ-PGA)和/或其盐类；以及b)一用于γ-PGA和/或其盐类的眼部可接受水性载体，用以冲洗患者的眼部组织。本发明还公开一种眼科手术冲洗液及医药套组，以降低眼科手术期间压力对眼部组织引发的伤害。Ophthalmic irrigating solutions are disclosed. The ophthalmic irrigating solution comprises: a) γ-polyglutamic acid (γ-PGA) and/or salt thereof in an amount effective to increase the viscosity of the irrigating solution, and b) an ophthalmically acceptable aqueous vehicle for the γ-PGA and/or salt thereof. Also disclosed is a method of irrigating ocular tissues of a patient, in which the method comprises introducing to the ocular tissues of the patient an ophthalmic irrigating solution comprising γ-PGA) and/or salt thereof in an amount sufficient to irrigate the ocular tissues of the patient
Gamma-polyglutamic acid-based ocular irrigating solutions
No full text[[abstract]]Ophthalmic irrigating solutions are disclosed. The ophthalmic irrigating solution comprises: a) γ-polyglutamic acid (γ-PGA) and/or salt thereof in an amount effective to increase the viscosity of the irrigating solution, and b) an ophthalmically acceptable aqueous vehicle for the γ-PGA and/or salt thereof. Also disclosed is a method of irrigating ocular tissues of a patient, in which the method comprises introducing to the ocular tissues of the patient an ophthalmic irrigating solution comprising γ-PGA) and/or salt thereof in an amount sufficient to irrigate the ocular tissues of the patient