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Heterocyclic compounds and use thereof
No full text[[abstract]]FIELD: chemistry.SUBSTANCE: invention relates to a novel heterocyclic compound of formula (I). In formula (I), each of Rand Rindependently represents H, a halogen atom, an amino, Calkyl, Cheterocycloalkyl containing in ring 1–2 nitrogen atoms or nitrogen atom and oxygen atom; or Rand Rtogether with two carbon atoms to which they are bonded, are Cheterocycloalkyl containing a nitrogen atom as a heteroatom, phenyl or 5-member heteroaryl containing a nitrogen atom in the cycle, a sulphur atom or two nitrogen atoms, where each of the Cheterocycloalkyl, phenyl and heteroaryl is optionally substituted with a halogen atom, Calkyl, Calkoxy or C(O)OR, in which Ris H or Calkyl; and each of Rand Rindependently represents NRR,or, wherein at least one of Rand Ris, in which each of Rand Rindependently represents H or Calkyl; Ris H, Calkyl, benzyl, optionally substituted cyano, or 5-member heteroaryl Calkyl containing 2 nitrogen atoms as heteroatoms; Ris H; Lis 5-member heteroaryl containing 3 nitrogen atoms as heteroatoms, Cheterocycloalkyl containing 1–2 nitrogen atoms in a cycle, NH or NR, in which Ris C(O)(CH)CHNHCOR, where Ris H or Calkyl; Ris H, Calkyl, Calkoxy, Ccycloalkyl, Cheterocycloalkyl containing in the cycle a nitrogen atom or a nitrogen atom and an oxygen atom, phenyl or 5- or 6-member heteroaryl containing 1–3 nitrogen atoms as heteroatoms, wherein each of said Calkyl, Calkoxy, Ccycloalkyl, Cheterocycloalkyl, phenyl and heteroaryl is optionally substituted with hydroxy, hydroxy Calkyl, halogen atom, amino Calkyl, amino Ccycloalkyl, amino Cheterocycloalkyl, Ccycloalkyl, Cheterocycloalkyl containing a nitrogen atom and an oxygen atom in the cycle, phenyl, optionally substituted with halogen, or 5-member heteroaryl containing 2 nitrogen atoms as heteroatoms; m is 1–6; n is equal to 2–3; each of Rand Rindependently represents H or Calkyl; or Rand Rtogether with nitrogen atoms with which they are bonded, are Cheterocycloalkyl; Lis Calkyl; or Ltogether with Ror Rand nitrogen atom, with which they are bonded, is Cheterocycloalkyl. Other radical values are specified in the patent claim.EFFECT: compound has activity on CXCR4 type 4 chemokine receptor (CXCR4) and can be used for treating a disease selected from renal damage, ischemic disease, cancer and myocardial infarction; and the compound can also be used to mobilize haemopoetic stem cells (HSC) and endothelial progenitor cells (EEC) in peripheral circulation.29 cl, 4 e
Heterocyclic compounds and use thereof
No full text[[abstract]]Heterocyclic compounds of Formula (I) shown herein. Also disclosed are pharmaceutical compositions containing the heterocyclic compounds and methods of using the heterocyclic compounds to mobilize hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation. Further provided are methods for treating tissue injury, cancer, inflammatory disease, and autoimmune disease with the heterocyclic compounds
杂环化合物及其用途
No full text[[abstract]]本发明是关于式(I)的杂环化合物，另揭露包含该杂环化合物的药物组合物以及使用该杂环化合物驱使造血干细胞(HSC)及内皮前驱细胞(EPC)进入周边血液循环的方法。本发明更提供一种使用该杂环化合物治疗组织损伤、癌症、发炎性疾病、或自体免疫性疾病的方法
雜環化合物及其用途
No full text[[abstract]]本發明是關於式(I)的雜環化合物，另揭露包含該雜環化合物的藥物組合物以及使用該雜環化合物驅使造血幹細胞(HSC)及內皮前驅細胞(EPC)進入周邊血液循環的方法。本發明更提供一種使用該雜環化合物治療組織損傷、癌症、發炎性疾病、或自體免疫性疾病的方法
[[alternative]]TCF12 and LncRNA MALAT1 Cooperatively Harness High Cyclin D1 but Low β-Catenin Gene Expression to Exacerbate Colorectal Cancer Prognosis Independently of Metastasis
No full text[[abstract]]Metastasis is a well-known factor worsening colorectal cancer (CRC) prognosis, but mortality mechanisms in non-metastatic patients with poor outcomes are less understood. TCF12 is a transcription factor that can be physically associated with the long non-coding RNA MALAT1, creating an alliance with correlated expression levels in CRC patients. This TCF12-MALAT1 alliance is linked to poorer prognosis independently of age and metastasis. To identify the downstream effects responsible for this outcome, we analyzed 2312 common target genes of TCF12 and MALAT1, finding involvement in pathways like Aurora B, ATM, PLK1, and non-canonical WNT. We investigated the impact of WNT downstream genes CTNNB1 and CCND1, encoding beta-catenin and cyclin D1, respectively, on survival in CRC patients with this alliance. Tumors with higher TCF12 and MALAT1 gene expressions alongside increased beta-catenin gene expressions were classified as having a "Pan-CMS-2 pattern", showing relatively better prognoses. Conversely, tumors with high TCF12, MALAT1, and cyclin D1 gene expressions but low beta-catenin expression were categorized as "TMBC pattern", associated with poor survival, with survival rates dropping sharply from 60% at one year to 30% at three years. This suggests that targeting cyclin D1-associated CDK4/6 could potentially reduce early mortality risks in TMBC patients, supporting personalized medicine approaches
Neurofilament light chain and cognitive function among OSA patients
No full text[[abstract]]Introduction: Obstructive Sleep apnea (OSA) is characterized by intermittent hypoxia during sleep, leading to cognitive impairment. Neurofilament light chain (NFL) is a biomarker for brain nerve damage, it's level increased in peripheral blood in neurodegenerative diseases. The increase in NfL has been hypothesized to be related with sleep loss, sleep architecture change, and intermittent hypoxia. Methods: We recruited 18 adult patients with OSA between October 2023 and December 2023. The patients underwent in-laboratory polysomnographic studies, a smart-phone based psychomotor vigilance test (PVT), and blood test for level of NFL. Endotypic traits including arousal threshold, upper airway collapsibility, loop gain, and upper airway muscle compensation, hypoxic burden, apnea and hypopnea duration were generated using polysomnographic signals. We examined the correlation between PVT results and blood NFL level. We further used multivariate linear regression model to examine the association between endotypic traits of OSA with blood NFL level. Results: The study participants had an average apnea-hypopnea index (AHI) 49.3 ± 27.5/h, and NFL 10.5 ± 8.4 pg/mL. We observed a negative relationship between mean reciprocal reaction time in PVT and NFL level (r = _0.79, p < 0.001). After adjustment for age, sex, and body-mass index, AHI was positively associated with NFL level (β = 0.17, 95% confidence interval = 0.04–0.30, p = 0.02). However, endotypic traits were not associated with NFL level. After additional adjustment for AHI, the proportion of slow-wave sleep was negatively associated with NFL level, whereas rapid-eye movement sleep was positively associated with NFL. Conclusions: NFL level is correlated with worse attention performance among OSA patients. Our findings did not observe an association between hypoxic burden of OSA and neurodegeneration biomarker. Instead, slow-wave sleep deprivation is associated with neurodegeneration in OSA patients
Prostate cancer cells elevate glycolysis and G6PD in response to caffeic acid phenethyl ester-induced growth inhibition
No full text[[abstract]]BackgroundCaffeic acid phenethyl ester (CAPE) is the main bioactive component of poplar type propolis. We previously reported that treatment with caffeic acid phenethyl ester (CAPE) suppressed the cell proliferation, tumor growth, as well as migration and invasion of prostate cancer (PCa) cells via inhibition of signaling pathways of AKT, c-Myc, Wnt and EGFR. We also demonstrated that combined treatment of CAPE and docetaxel altered the genes involved in glycolysis and tricarboxylic acid (TCA) cycle. We therefore suspect that CAPE treatment may interfere glucose metabolism in PCa cells.MethodsSeahorse Bioenergetics platform was applied to analyzed the extra cellular acidification rate (ECAR) and oxygen consumption rate (OCR) of PCa cells under CAPE treatment. UPLC-MSMS with Multiple Reaction Monitoring (MRM), PCR, and western blot were used to analyze the effects of CAPE on metabolites, genes, and proteins involved in glycolysis, TCA cycle and pentose phosphate pathway in PCa cells. Flow cytometry and ELISA were used to determine the level of reactive oxygen species in PCa cells being treated with CAPE.ResultsSeahorse Bioenergetics analysis revealed that ECAR, glycolysis, OCR, and ATP production were elevated in C4-2B cells under CAPE treatment. Protein levels of glucose-6-phosphate dehydrogenase (G6PD), phosphogluconate dehydrogenase (PGD), glutaminase (GLS), phospho-AMPK Thr172 as well as abundance of pyruvate, lactate, ribulose-5-phosphate, and sedoheptulose-7-phosphate were increased in CAPE-treated C4-2B cells. ROS level decreased 48 h after treatment with CAPE. Co-treatment of AMPK inhibitor with CAPE exhibited additive growth inhibition on PCa cells.ConclusionsOur study indicated that PCa cells attempted to overcome the CAPE-induced stress by upregulation of glycolysis and G6PD but failed to impede the growth inhibition caused by CAPE. Concurrent treatment of CAPE and inhibitors targeting glycolysis may be effective therapy for advanced PCa
抗RSPO3抗体
No full text[[abstract]]An isolated antibody, comprising: heavy chain complementary determining regions CDR1, CDR2, and CDR3 of a heavy chain variable region sequence selected from SEQ ID NOs: 2, 6, 10, and 14; and light chain complementary determining regions CDR1, CDR2, and CDR3 of a light chain variable region sequence selected from SEQ ID NOs: 4, 8, 12, and 16; wherein the antibody binds specifically to a RSPO3 protein
[[alternative]]Aminothiazole compounds and use thereof
No full text[[abstract]]本發明提供一種如式(I)之氨基噻唑化合物及包含其之醫藥組合物。本發明亦提供使用氨基噻唑化合物之一者來抑制蛋白激酶或治療與蛋白激酶相關之癌症的方法
氨基噻唑化合物及其用途
No full text[[abstract]]本發明提供本文所示的式(I)的氨基噻唑化合物及包含此類化合物中的一種的藥物組合物。本發明還公開分別使用所述氨基噻唑化合物中的一種來抑制蛋白激酶或治療與蛋白激酶相關的癌症的多種方法