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1.
Insects ; 15(7)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39057197

RESUMO

The firefly genus Oculogryphus Jeng, Engel & Yang, 2007 is a rare-species group endemic to Asia. Since its establishment, its position has been controversial but never rigorously tested. To address this perplexing issue, we are the first to present the complete mitochondrial sequence of Oculogryphus, using the material of O. chenghoiyanae Yiu & Jeng, 2018 determined through a comprehensive morphological identification. Our analyses demonstrate that its mitogenome exhibits similar characteristics to that of Stenocladius, including a rearranged gene order between trnC and trnW, and a long intergenic spacer (702 bp) between the two rearranged genes, within which six remnants (29 bp) of trnW were identified. Further, we incorporated this sequence into phylogenetic analyses of Lampyridae based on different molecular markers and datasets using ML and BI analyses. The results consistently place Oculogryphus within the same clade as Stenocladius in all topologies, and the gene rearrangement is a synapomorphy for this clade. It suggests that Oculogryphus should be classified together with Stenocladius in the subfamily Ototretinae at the moment. This study provides molecular evidence confirming the close relationship between Oculogryphus and Stenocladius and discovers a new phylogenetic marker helpful in clarifying the monophyly of Ototretinae, which also sheds a new light on firefly evolution.

3.
Nat Prod Res ; : 1-5, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867712

RESUMO

Two new alkenyl phenol derivatives, namely pestalol F (1) and pestalol G (2), along with two known compounds, pestalachloride A (3) and pestalotiopsin J (4), were isolated from the culture of the fungus Pestalotiopsis clavata JSQ 12. The structures of these compounds were primarily elucidated by MS, NMR and specific rotation data analysises. These secondary metabolites of Pestalotiopsis clavata were reported for the first time. Compound 2 displayed interesting cytotoxic activity against MCF-7 cell line with the IC50 value of 29.16 µM, whereas compound 3 exhibited moderate activity towards A549 cell line with the IC50 value of 35.71 µM. The positive control 5-FU showed cytotoxic effects on MCF-7 and A549 cell lines with the respective IC50 values of 26.70 and 26.07 µM. Compounds 1 and 2 displayed mild antibacterial activities against Staphylococcus aureus with MIC values of 128 and 64 µg/mL (MIC of positive control, penicillin, was 0.016 µg/mL), respectively.

4.
J Ethnopharmacol ; 330: 118208, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38636581

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zhilong Huoxue Tongyu Capsule (ZL) is clinically prescribed for acute ischemic stroke (AIS). However, only a few studies have addressed the mechanisms of ZL in treating AIS. AIM OF THE STUDY: To explore the underlying mechanism of macrophage polarization and inflammation mediated by ZL, and to provide a reference for AIS treatment. MATERIALS AND METHODS: Sixteen SD rats were fed with different dose of ZL (0, 0.4, 0.8, and 1.6 g/kg/d) for 4 days to prepare ZL serum. After 500 ng/mL lipopolysaccharide (LPS) stimulation, RAW264.7 cells were administrated with ZL serum. Then, experiments including ELISA, flow cytometry, real-time quantitative PCR and Western blot were performed to verify the effects of ZL on macrophage polarization and inflammation. Next, let-7i inhibitor was transfected in RAW264.7 cells when treated with LPS and ZL serum to verify the regulation of ZL on the let-7i/TLR9/MyD88 signaling pathway. Moreover, the interaction between let-7i and TLR9 was confirmed by the dual-luciferase assay. RESULTS: ZL serum significantly decreased the expression of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and increased the expression of IL-10 and transforming growth factor ß1 (TGF-ß1) of LPS stimulated-macrophages. Furthermore, ZL serum polarized macrophages toward M2, decreased the expressions of TLR9, MyD88, and iNOS, as well as increased the expressions of let-7i, CHIL3, and Arginase-1. It is worth mentioning that the effect of ZL serum is dose-dependent. However, let-7i inhibitor restored all the above effects in LPS stimulated-macrophages. In addition, TLR9 was the target of let-7i. CONCLUSIONS: ZL targeted let-7i to inhibit TLR9 expression, thereby inhibiting the activation of the TLR9/MyD88 pathway, promoting the M2 polarization, and inhibiting the development of inflammation in AIS.


Assuntos
Medicamentos de Ervas Chinesas , Macrófagos , MicroRNAs , Fator 88 de Diferenciação Mieloide , Ratos Sprague-Dawley , Transdução de Sinais , Receptor Toll-Like 9 , Animais , Fator 88 de Diferenciação Mieloide/metabolismo , Camundongos , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Receptor Toll-Like 9/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , MicroRNAs/metabolismo , Ratos , Masculino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos , Anti-Inflamatórios/farmacologia
5.
Nat Commun ; 15(1): 3149, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605037

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo
6.
Biotechnol J ; 19(3): e2300642, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38472088

RESUMO

The biosynthesis of cadaverine from lysine is an environmentally promising technology, that could contribute to a more sustainable approach to manufacturing bio-nylon 5X. However, the titer of biosynthesized cadaverine has still not reached a sufficient level for industrial production. A powerful green cell factory was developed to enhance cadaverine production by regulating lipopolysaccharide (LPS) genes and improving membrane permeability. Firstly, 10 LPS mutant strains were constructed and the effect on the growth was investigated. Then, the lysine decarboxylase (CadA) was overexpressed in 10 LPS mutant strains of Escherichia coli MG1655 and the ability to produce cadaverine was compared. Using 20.0 g L-1 of L-lysine hydrochloride (L-lysine-HCl) as the substrate for the biotransformation reaction, Cad02 and Cad06 strains exhibited high production levels of cadaverine, with 8.95 g L-1 and 7.55 g L-1 respectively while the control strain Cad00 only 4.92 g L-1 . Directed evolution of CadA was also used to improve its stability under alkaline conditions. The cadaverine production of the Cad02-M mutant stain increased by 1.86 times at pH 8.0. Finally, the production process was scaled up using recombinant whole cells as catalysts, achieving a high titer of 211 g L-1 cadaverine (96.8%) by fed-batch bioconversion. This study demonstrates the potential role of LPS in enhancing the efficiency of mass transfer between substrate and enzymes in vivo by increasing cell permeability. The results indicate that the argumentation of cell permeability could not only significantly enhance the biotransformation efficiency of cadaverine, but also provide a universally applicable, straightforward, environment-friendly, and cost-effective method for the biosynthesis of other high-value chemicals.


Assuntos
Escherichia coli , Lipopolissacarídeos , Escherichia coli/genética , Cadaverina/metabolismo , Lipopolissacarídeos/metabolismo , Catálise , Biotransformação , Lisina/metabolismo
8.
Phytopathology ; : PHYTO07230227R, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37913633

RESUMO

Plant viruses produce particular suppressors to antagonize the host defense response of RNA silencing to establish infection. Cucurbit chlorotic yellows virus (CCYV), a member of the genus Crinivirus of the family Closteroviridae, severely damages the production of economically essential cucurbits worldwide. Here, we used the attenuated zucchini yellow mosaic virus (ZYMV) vector ZAC to express individual coding sequences, including CP, CPm, P25, and P22, of a Taiwan CCYV isolate (CCYV-TW) to identify their possible roles as pathogenicity determinants. ZAC is an HC-Pro function mutant that lacks the ability of local lesion induction on Chenopodium quinoa leaves and induces mild mottling followed by recovery on its natural host zucchini squash plants. Only the recombinant expressing CCYV-TW P22 complemented the effect of ZAC HC-Pro dysfunction, causing more severe symptoms on zucchini squash plants and restoring lesion formation on C. quinoa leaves, with lesions forming faster than those generated by the wild-type ZYMV. This suggests that CCYV-TW P22 is a virulence enhancer. Sequence analysis of criniviral P22s revealed the presence of four conserved leucine residues (L10, L17, L84, and L127) and one conserved lysine residue (K185). The five P22 residues conserved among the CCYV isolates and the P22 orthologs of two other criniviruses were each substituted with alanine in CCYV-TW P22 to investigate its ability to suppress RNA silencing and pathogenicity. The results provide new insights into CCYV-P22, showing that the L127 residue of P22 is indispensable for maintaining its stability in RNA silencing suppression and essential for virulence enhancement.

9.
Cancer Med ; 12(19): 20119-20128, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37740620

RESUMO

BACKGROUND: Pancreatic cancer is often diagnosed at a late stage with a poor prognosis due to insidious symptoms and lack of evidence-based screening in general population. Palliative care's acceptance in Asian cultures is hindered by misconceptions and ineffective communication about management that improve quality of life other than cancer directed treatment. Our study aimed to determine the effect of the Shared decision-making with Oncologists and Palliative care specialists (SOP) model developed from the traditional shared decision-making (SDM) model on the palliative care acceptance rate and medical resource utilization. METHODS: This is a prospective cohort study implementing the SOP model at the National Taiwan University Hospital from January 2018 to December 2019 for patients with advanced pancreatic cancer. Medical resource utilization was defined and recorded as the rate of hospitalization, emergency room (ER), and intensive care unit admissions. We compared the results between two groups: patients who received the SOP model in 2019 and patients who did not receive it in 2018. RESULTS: 137 patients with advanced pancreatic cancer were included in our study. The result showed that the acceptance rate of palliative care significantly increased from 50% to 78.69% after the SOP model (p = 0.01). The hospitalization rate did not show a significant difference between 2018 (93.42%, 95% CI: 0.88-0.99) and 2019 (93.44%, 95% CI: 0.87-1.00). 83.61% (95% CI: 0.74-0.93) of our patients in 2019 had at least one ER visit; the rate was 81.5% (95% CI: 0.73-0.91) in 2018 (p = 0.28). The percentage of patients admitted to the ICU increased from 3.95% in 2018 to 8.2% (95% CI: -0.05-0.08) in 2019 (95% CI: 0.11-0.15) (p = 0.00). The hospitalization and ER visit showed no statistically difference between 2 years. CONCLUSIONS: The modified SOP model markedly augmented palliative care's acceptance of patients with advanced pancreatic cancer. Adoption of the SOP model would provide these patients a more proactive and systematic approach to deliver needed healthcare.


Assuntos
Oncologistas , Neoplasias Pancreáticas , Humanos , Cuidados Paliativos/métodos , Tomada de Decisão Compartilhada , Qualidade de Vida , Objetivos , Estudos Prospectivos , Neoplasias Pancreáticas/terapia , Tomada de Decisões , Neoplasias Pancreáticas
10.
Mitochondrial DNA B Resour ; 8(8): 847-851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576983

RESUMO

The genus Themus Motschulsky, 1858 is one of the largest genera of beetle family Cantharidae, however, no complete mitochondrial genome is available in the public database so far. Here, we sequenced and analyzed the first complete mitochondrial genome of Themus, with T. foveicollis as the representative species. The mitochondrial genome was 16,469 bp in size with 37 genes including 13 protein-coding genes (PCGs), 22 transfer RNA genes, and two ribosomal RNA genes, as well as a non-coding region, which are arranged in the same way as the hypothetical ancestral insect. It exhibited a typical high A + T bias and a higher proportion of bases A and C than T and G (A: 41.1%, T: 37.5%, G: 8.6%, C: 12.9%). The phylogenetic trees of Elateroidea were reconstructed based on 13 PCGs sequences using the Bayesian inference (BI) and maximum-likelihood (ML) analyses to investigate its phylogenetic position. The results showed that Themus was consistently grouped with the remaining genera of Cantharidae and placed in a monophyletic clade of Cantharinae in high supporting values, which are congruent with the morphological classification. The newly sequenced mitochondrial genome in this study constitutes important reference data for reconstructing phylogeny of the family Cantharidae or the superfamily Elateroidea.

11.
Nanoscale ; 15(18): 8181-8188, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37078095

RESUMO

Metal-organic framework (MOF)-derived metal oxide semiconductors have recently received extensive attention in gas sensing applications due to their high porosity and three-dimensional architecture. Still, challenges remain for MOF-derived materials, including low-cost and facile synthetic methods, rational nanostructure design, and superior gas-sensing performances. Herein, a series of Fe-MIL-88B-derived trimetallic FeCoNi oxides (FCN-MOS) with a mesoporous structure were synthesized by a one-step hydrothermal reaction followed by calcination. The FCN-MOS system consists of three main phases: α-Fe2O3 (n-type), CoFe2O4, and NiFe2O4 (p-type), and the nanostructure and pore size can be controlled by altering the content of α-Fe2O3, CoFe2O4, and NiFe2O4. The sensors based on FCN-MOS exhibit a high response of 71.9, a good selectivity towards 100 ppm ethanol at 250 °C, and long-term stability up to 60 days. Additionally, the FCN-MOS-based sensors show a p-n transition gas sensing behavior with the alteration of the Fe/Co/Ni ratio.

12.
J Ethnopharmacol ; 312: 116521, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37080368

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hemorrhagic transformation after acute ischemic stroke is a life-threatening disease that currently has no effective chemotherapy. Zhilong Huoxue Tongyu Capsule (ZL) is an empirical prescription of traditional Chinese medicine that is used to prevent and treat cardiovascular and cerebrovascular diseases in China. However, only a few studies have addressed the mechanisms of ZL in treating hemorrhagic transformation. AIM OF THE STUDY: To evaluate the anti-inflammatory effects of ZL on hemorrhagic transformation model rats and lipopolysaccharide (LPS)-induced RAW264.7 macrophages and to explore the underlying molecular mechanisms. MATERIALS AND METHODS: Murine RAW264.7 cells were treated with ZL and LPS (1 µg/mL), and cell viability was detected by cell counting kit-8 assay. RT-qPCR was used to detect the expression of inflammatory chemokines, microRNA let-7a/e/i/f, toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-B (NF-κB) p65. The protein expression levels of TLR4, MyD88, NF-κB p65, and apoptosis related molecules were determined by Western blotting. The apoptosis rate of RAW264.7 macrophages was detected by Annexin V-FITC/PI double staining. A hemorrhagic transformation model in rats was established by intraperitoneal injection of high glucose solution combined with thread embolization. Then, the model rats were observed behaviourally, pathologically, and molecularly. The gene expression of TLR4, MyD88, and NF-κB p65 was measured by RT-qPCR and used to evaluate the protective effect of ZL against hemorrhagic transformation in rats. RESULTS: ZL (5, 20, 40 µg/mL) was beneficial in cell proliferation. LPS (1 µg/mL) stimulated the production of inflammatory chemokines and inhibited the production of let-7a/e/i/f, with let-7f being influenced most strongly. Moreover, overexpression of let-7f decreased the gene and protein levels of TLR4, MyD88, and NF-κB p65, downregulated TLR4, and inhibited its transcriptional activity. ZL (5, 20, and 40 µg·mL-1) inhibited the production of TLR4, MyD88, and NF-κB p65 and promoted the production of let-7f in a concentration-dependent manner. Furthermore, the blockade of TLR4 antagonized the promoting effects of TLR4 pathway activation in cell inflammation and apoptosis by downregulating let-7f. Critically, it was confirmed in vivo and in vitro that ZL upregulated the expression of let-7f and inhibited the gene expression of TLR4, MyD88, and NF-κB p65 to reduce inflammatory cell infiltration, which determined the occurrence of hemorrhagic transformation. CONCLUSIONS: ZL can reduce inflammatory response by upregulating let-7f and subsequently inhibiting the TLR4 signaling pathway, thereby decreasing the occurrence of hemorrhagic transformation.


Assuntos
AVC Isquêmico , NF-kappa B , Ratos , Camundongos , Animais , NF-kappa B/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Lipopolissacarídeos/farmacologia , Transdução de Sinais
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(1): 76-80, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36765480

RESUMO

OBJECTIVE: To investigate the effects of miR-144-3p on cell proliferation, cell cycle and apoptosis of blast phase chronic myelogenous leukemia (CML) K562 cells. METHODS: K562 cells were cultured in vitro and mimics negative control, hsa-miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor were respectively transfected into K562 cells with transfection reagents. The cells were divided into five groups including blank control, mimics negative control, miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor. After transfection, the cell proliferation activity was detected by CCK-8 assay. The cell cycle distribution and apoptosis were detected by flow cytometry. RESULTS: Compared with the blank control and mimics negative control groups, the proliferation rate of miR-144-3p mimics group was significantly decreased (P<0.05), the proportion of S phase cells was markedly increased (P<0.05), while the proportion of G1 phase cells was obviously decreased (P<0.05), and the apoptosis rate was significantly increased (P<0.05). Compared with the blank control and inhibitor negative control groups, the proliferation rate of miR-144-3p inhibitor group was obviously increased (P<0.05), the proportion of S phase cells was markedly decreased (P<0.05), while the proportion of G1 phase cells was obviously increased (P<0.05), and the apoptosis rate was significantly decreased (P<0.05). CONCLUSION: miR-144-3p can inhibit the proliferation and promote apoptosis of K562 cells, affect the cell cycle, and block K562 cells in S phase, which indicates that miR-144-3p is involved in the cell cycle activity of CML during blastic phase.


Assuntos
MicroRNAs , Humanos , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Células K562 , MicroRNAs/genética , MicroRNAs/metabolismo
14.
Environ Sci Pollut Res Int ; 30(12): 32866-32881, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36472738

RESUMO

Hydrothermal treatment (HT) is envisaged as a promising technology to treat the lignocellulosic biomass. HT temperature is an important parameter influencing the hydrolysate compositions such as organic compounds and potential inhibitors, and therefore affect the subsequential anaerobic digestion (AD) process. Herein, HT-AD was employed to treat the wheat straw-derived digestate. The HT temperature of 190 °C was proved to be the best performance with a higehst reducing sugar yield (45.05 mg g-1) in the hydrolysate and a highest methane yield (120.8 mL gTS-1) from the AD of the hydrolysate, which was 42.5% higher than the methane yield in the control without the hydrolysate addition (84.8 mL gTS-1). 3-Furaldehyde was the dominant organic in the hydrolysates. The HT temperature of 210 °C led to the presence of AD inhibitory moieties (e.g., phenols and furans) in the hydrolysate, resulting in a low methane yield. Although the treatments with the addition of 100% hydrolysate outperformed those of 50% hydrolysate in the methane yields in the late stage, the latter had higher methane yields in the first stage, suggesting that the additional ratios of hydrolysates should be carefully considered in AD, especially the detrimental effects of inhibitors and adaptability issues of AD consortia. The MiSeq sequencing showed that the hydrolysis/acidogenesis was dominant in the first stage, while methanogenesis became dominant in the late stage with the acetoclastic/hydrogenotrophic methanogens (Methanosarcina and Methanobacterium) enriched in the hydrolysate-feeding reactors. These findings demonstrated that a integration of HT-AD was a promising approach for the digestate valorization and to reduce the potential carbon emission from waste treatments.


Assuntos
Lignina , Metano , Anaerobiose , Temperatura , Lignina/metabolismo , Reatores Biológicos , Biocombustíveis
15.
Insects ; 13(12)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36555081

RESUMO

The lycid genus Mesolycus Gorham, 1883 is mainly distributed in East Palaearctic and Indochinese regions, but poorly studied in China; moreover, its phylogenetic placement remains controversial but has never been rigorously tested. In this study, Mesolycus was reviewed and its placement within Lycidae was tested based on a multilocus phylogeny (cox1, nad5, cox2 and Lrna) by both ML and BI analyses. The reconstructed phylogenies show that Mesolycus is a consistently recovered sister to Dilophotes Waterhouse, 1879, and they form a monophyletic clade which is well supported. This suggests that Mesolycus definitely belongs to Dilophotini rather than to Macrolycini of Lycinae. Besides, three species originally described or placed in Dilophotes are transferred to Mesolycus, including M. atricollis (Pic, 1926) comb. n., M. particularis (Pic, 1928) comb. n. and M. pacholatkoi (Bic, 2002) comb. n. Four new species are discovered in China, including M. shaanxiensis sp. n., M. dentatus sp. n., M. breviplatus sp. n. and M. varus sp. n. Two species, M. murzini Kazantsev, 2004 and M. rubromarginatus Kazantsev, 2013, are recorded from China for the first time. A key for the identification of all Mesolycus species is provided. China was revealed as the region with the highest species diversity of this genus.

16.
J Clin Invest ; 132(24)2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36282600

RESUMO

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care regimens. Differences between ODSA results and patient tumor responses were assessed by exact McNemar's test.RESULTSImmunofluorescence signals, organoid growth curves, and Ki-67 levels were measured and authenticated through the OBP for up to 14 days. ODSA drug responses were not different from patient tumor responses, as reflected by CA19-9 reductions following neoadjuvant chemotherapy (P = 0.99). PDOs demonstrated unique apoptotic and tumor-stroma modulation profiles (P < 0.0001). α-SMA/CK-19 ratio levels of more than 1.0 were associated with improved outcomes (P = 0.0179) and longer parental patient survival by Kaplan-Meier analysis (P = 0.0046).CONCLUSIONHeterogenous apoptotic drug responses and tumor-stroma modulation are present in PDOs after standard-of-care chemotherapy. Ratios of α-SMA and CK-19 levels in PDOs are associated with patient survival, and the OBP could aid in the selection of personalized therapies to improve the efficacy of systemic therapy in patients with PDAC.FUNDINGNIH/National Cancer Institute grants (K08CA218690, P01 CA117969, R50 CA243707-01A1, U54CA224065), the Skip Viragh Foundation, the Bettie Willerson Driver Cancer Research Fund, and a Cancer Center Support Grant for the Flow Cytometry and Cellular Imaging Core Facility (P30CA16672).


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Medicina de Precisão , Estudos Retrospectivos , Imageamento Tridimensional , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Organoides/patologia , Neoplasias Pancreáticas
18.
Cell Oncol (Dordr) ; 45(5): 893-909, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35930163

RESUMO

PURPOSE: Although YAP1 and TAZ are believed to be equivalent downstream effectors of the Hippo pathway, differential expression of YAP1 or TAZ suggests distinct functions during cancer progression. The exact role of YAP1 and TAZ in esophageal cancer, the 6th leading cancer-related mortality in the world, remains elusive. METHODS: Following single or double manipulation of YAP1 or TAZ expression, we subjected these manipulated cells to proliferation, migration, invasion, and xenograft tumorigenesis assays. We used RT-qPCR and Western blotting to examine their expression in the manipulated cells with or without inhibition of transcription or translation. We also examined the impact of YAP1 or TAZ deregulation on clinical outcome of esophageal cancer patients from the TCGA database. RESULTS: We found that YAP1 functions as a tumor suppressor whereas TAZ exerts pro-tumor functions in esophageal cancer cells. We also found a significant increase in TAZ mRNA expression upon YAP1 depletion, but not vice versa, despite the downregulation of CTGF and CYR61, shared targets of YAP1 and TAZ, in xenografted tissue cells. In addition to transcriptional regulation, YAP1-mediated TAZ expression was found to occur via protein synthesis. Restored TAZ expression mitigated YAP1-mediated suppression of cellular behavior. By contrast, TAZ silencing reduced the promoting effect exerted by YAP1 depletion on cellular behaviors. The observed anti-tumor function of YAP1 was further supported by a better overall survival among esophageal cancer patients with a high YAP1 expression. CONCLUSION: From our data we conclude that YAP1 functions as a suppressor and negatively regulates pro-tumor TAZ expression via transcriptional and translational control in esophageal cancer.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Esofágicas/genética , Transdução de Sinais/genética , RNA Mensageiro/genética
19.
Front Neurosci ; 16: 915164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860295

RESUMO

Radiation-induced functional and structural brain alterations are well documented in patients with nasopharyngeal carcinoma (NPC), followed by radiotherapy (RT); however, alterations in structure-function coupling remain largely unknown. Herein, we aimed to assess radiation-induced structure-function decoupling and its importance in predicting radiation encephalopathy (RE). We included 62 patients with NPC (22 patients in the pre-RT cohort, 18 patients in the post-RT-RE+ve cohort, and 22 patients in the post-RT-RE-ve cohort). A metric of regional homogeneity (ReHo)/voxel-based morphometry (VBM) was used to detect radiation-induced structure-function decoupling, which was then used as a feature to construct a predictive model for RE. Compared with the pre-RT group, patients in the post-RT group (which included post-RT-RE+ve and post-RT-RE-ve) showed higher ReHo/VBM coupling values in the substantia nigra (SN), the putamen, and the bilateral thalamus and lower values in the brain stem, the cerebellum, the bilateral medial temporal lobes (MTLs), the bilateral insula, the right precentral and postcentral gyri, the medial prefrontal cortex (MPFC), and the left inferior parietal lobule (IPL). In the post-RT group, negative correlations were observed between maximum dosage of RT (MDRT) to the ipsilateral temporal lobe and ReHo/VBM values in the ipsilateral middle temporal gyrus (MTG). Moreover, structure-function decoupling in the bilateral superior temporal gyrus (STG), the bilateral precentral and postcentral gyri, the paracentral lobules, the right precuneus and IPL, and the right MPFC exhibited excellent predictive performance (accuracy = 88.0%) in identifying patients likely to develop RE. These findings show that ReHo/VBM may be a novel effective imaging metric that reflects the neural mechanism underlying RE in patients with NPC.

20.
Ann Transl Med ; 10(8): 460, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571442

RESUMO

Background: The adoption of appropriate health behaviors can prevent the recurrence of stroke. Previous research found a downward trend in hypertensive stroke patients' health behaviors from 3 to 6 months after discharge. The provision of appropriate support by chronic illness resources has been shown to predict patients' engagement in appropriate health behaviors in other chronic illness populations. This study sought to explore the association between chronic illness resources and health behaviors in hypertensive stroke patients in order to provide a foundation for the secondary prevention of stroke. Methods: Using convenience sampling method, we enrolled 133 hypertensive stroke patients at 6 months after discharge in Guangzhou, China. All the patients completed a demographic and disease-specific questionnaire, the Health Behavior Scale for Stroke Patients (HBS-SP) and the Chronic Illness Resources Survey (CIRS). A multiple stepwise regression analysis was conducted to test the association of chronic illness resources with health behaviors. Results: The total scores of the HBS-SP and CIRS were (2.89±0.38) and (2.94±0.66), respectively. The correlation coefficient for chronic illness resources and health behaviors was 0.517 (P<0.001). The positive association between chronic illness resources and health behaviors remained statistically significant after controlling for gender, education level, and the Barthel Index (unstandardized coefficient: 0.317, P<0.001). Conclusions: The chronic illness resources has positive association with health behaviors in hypertensive stroke patients at 6 months after discharge. A good support provided by chronic illness resources may contribute to promote positive health behaviors, and thus prevent the recurrence of stroke.

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