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1.
Langmuir ; 40(37): 19689-19700, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39235286

RESUMO

Matrine (MT) is a kind of alkaloid extracted from Sophora and is a promising substitute for chemical nematicides and botanical pesticides. The present study utilized sodium alginate (SA), zeolite imidazole salt skeleton (ZIF), and MT as raw materials to prepare a pH-response-release nematicide through the electrostatic spray technique. Zinc metal-organic framework (ZIF-8) was initially synthesized, followed by the successful loading of MT. Subsequently, the electrostatic spray process was employed to encapsulate it in SA, resulting in the formation of MT/ZIF-8@SA microcapsules. The efficiency of encapsulation and drug loadings can reach 79.93 and 26.83%, respectively. Soybean cyst nematode (SCN) is one of the important pests that harm crops; acetic acid produced by plant roots and CO2 produced by root respiration causing a decrease in the pH of the surrounding environment, which is most attractive to the SCN when the pH is between 4.5 and 5.4. MT/ZIF-8@SA releases the loaded MT in response to acetic acid produced by roots and acidic oxides produced by root respiration. The rate of release was 37.67% higher at pH 5.25 compared with pH 8.60. The control efficiency can reach 89.08% under greenhouse conditions. The above results demonstrate that the prepared MT/ZIF-8@SA not only exhibited excellent efficacy but also demonstrated a pH-responsive release of the nematicide.


Assuntos
Alginatos , Alcaloides , Cápsulas , Glycine max , Matrinas , Quinolizinas , Eletricidade Estática , Alginatos/química , Alcaloides/química , Alcaloides/farmacologia , Animais , Concentração de Íons de Hidrogênio , Quinolizinas/química , Glycine max/química , Glycine max/parasitologia , Cápsulas/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Antinematódeos/química , Antinematódeos/farmacologia , Nematoides/efeitos dos fármacos , Liberação Controlada de Fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química
2.
Front Immunol ; 15: 1403070, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015575

RESUMO

Background: The cGAS-STING axis-mediated type I interferon pathway is a crucial strategy for host defense against DNA virus infection. Numerous evasion strategies developed by the pseudorabies virus (PRV) counteract host antiviral immunity. To what extent PRV-encoded proteins evade the cGAS-STING signaling pathway is unknown. Methods: Using US2 stably expressing cell lines and US2-deficient PRV model, we revealed that the PRV tegument protein US2 reduces STING protein stability and downregulates STING-mediated antiviral signaling. Results: To promote K48-linked ubiquitination and STING degradation, US2 interacts with the LBD structural domain of STING and recruits the E3 ligase TRIM21. TRIM21 deficiency consistently strengthens the host antiviral immune response brought on by PRV infection. Additionally, US2-deficient PRV is less harmful in mice. Conclusions: Our study implies that PRV US2 inhibits IFN signaling by a new mechanism that selectively targets STING while successfully evading the host antiviral response. As a result, the present study reveals a novel strategy by which PRV evades host defense and offers explanations for why the Bartha-K61 classical vaccine strain failed to offer effective defense against PRV variant strains in China, indicating that US2 may be a key target for developing gene-deficient PRV vaccines.


Assuntos
Herpesvirus Suídeo 1 , Imunidade Inata , Pseudorraiva , Transdução de Sinais , Proteínas do Envelope Viral , Animais , Humanos , Camundongos , Células HEK293 , Herpesvirus Suídeo 1/imunologia , Herpesvirus Suídeo 1/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Evasão da Resposta Imune , Proteínas de Membrana/metabolismo , Proteínas de Membrana/imunologia , Proteínas de Membrana/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/imunologia , Pseudorraiva/imunologia , Pseudorraiva/virologia , Ribonucleoproteínas/imunologia , Ribonucleoproteínas/metabolismo , Ubiquitinação , Proteínas do Envelope Viral/metabolismo
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 805-810, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38926971

RESUMO

OBJECTIVE: To evaluate the clinical and prognostic value of prothrombin time (PT) and activated partial thromboplastin time (APTT) in newly diagnosed patients with multiple myeloma (MM). METHODS: The clinical data of 116 newly diagnosed MM patients in the Second Hospital and Third Hospital of Shanxi Medical University from October 2014 to March 2022 were analyzed retrospectively, and the patients were divided into two groups: normal PT and APTT group and prolonged PT or APTT group. The differences in sex, age, classification, staging, bleeding events, laboratory indicators [including hemoglobin (Hb), platelet count (PLT), serum calcium, serum albumin (ALB), lactate dehydrogenase (LDH), serum creatinine and ß2-microglobulin], and cytogenetic characteristics between the two groups of patients were compared. The effect of prolonged PT or APTT on survival of patients with MM was analyzed. RESULTS: Compared with patients in normal PT and APTT group, patients in prolonged PT or APTT group were more likely to experience bleeding events (χ2=5.087, P =0.024), with lower ALB levels (χ2=4.962, P =0.026) and PLT levels (χ2=4.309, P =0.038), and higher serum calcium levels (χ2=5.056, P =0.025). The positive rates of del17p, del13q and 1q21+ in prolonged PT or APTT group were higher than those in normal PT and APTT group, but the difference was not statistically significant (P >0.05). K-M survival analysis showed that the prolonged PT or APTT group had a shorter median progression-free survival (PFS) (P =0.032) and overall survival (OS) (P =0.032). Multivariate Cox analysis showed that prolonged PT or APTT (HR=2.116, 95%CI :1.025-4.372, P =0.043) and age ≥65 years (HR=2.403, 95%CI : 1.195-4.836, P =0.014) were independent risk factor for OS in newly diagnosed MM patients. However, prolonged PT or APTT had no significant effect on PFS of newly diagnosed MM patients (HR=1.162, 95%CI : 0.666-2.026, P =0.597). CONCLUSION: Newly diagnosed MM patients with prolonged PT or APTT have worse clinical indicators, shorter PFS and OS. Prolonged PT or APTT is an independent risk factor for OS in MM patients.


Assuntos
Mieloma Múltiplo , Tempo de Protrombina , Humanos , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Tempo de Tromboplastina Parcial , Prognóstico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade
4.
Int Immunopharmacol ; 136: 112340, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38820962

RESUMO

BACKGROUND: Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-editing enzyme that significantly impacts cancer progression and various biological processes. The expression of ADAR1 mRNA has been examined in multiple cancer types using The Cancer Genome Atlas (TCGA) dataset, revealing distinct patterns in kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and liver hepatocellular carcinoma (LIHC) compared to normal controls. However, the reasons for these differential expressions remain unclear. METHODS: In this study, we performed RT-PCR and western blotting (WB) to validate ADAR1 expression patterns in clinical tissue samples. Survival analysis and immune microenvironment analysis (including immune score and stromal score) were conducted using TCGA data to determine the specific cell types associated with ADAR1, as well as the key genes in those cell types. The relationship between ADAR1 and specific cell types' key genes was verified by immunohistochemistry (IHC), using clinical liver and kidney cancer samples. RESULTS: Our validation analysis revealed that ADAR1 expression was downregulated in KICH, KIRC, and KIRP, while upregulated in LIHC compared to normal tissues. Notably, a significant correlation was found between ADAR1 mRNA expression and patient prognosis, particularly in KIRC, KIRP, and LIHC. Interestingly, we observed a positive correlation between ADAR1 expression and stromal scores in KIRC, whereas a negative correlation was observed in LIHC. Cell type analysis highlighted distinct relationships between ADAR1 expression and the two stromal cell types, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs), and further determined the signature gene claudin-5 (CLDN5), in KIRC and LIHC. Moreover, ADAR1 was inversely related with CLDN5 in KIRC (n = 26) and LIHC (n = 30) samples, verified via IHC. CONCLUSIONS: ADAR1 plays contrasting roles in LIHC and KIRC, associated with the enrichment of BECs and LECs within tumors. This study sheds light on the significant roles of stromal cells within the complex tumor microenvironment (TME) and provides new insights for future research in tumor immunotherapy and precision medicine.


Assuntos
Adenosina Desaminase , Carcinoma Hepatocelular , Carcinoma de Células Renais , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , Neoplasias Hepáticas , Proteínas de Ligação a RNA , Microambiente Tumoral , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Prognóstico , Feminino , Masculino , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade
5.
World J Hepatol ; 16(4): 537-549, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38689749

RESUMO

The tumor microenvironment is a complex network of cells, extracellular matrix, and signaling molecules that plays a critical role in tumor progression and metastasis. Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits. However, recent studies have shown that lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) also play multifaceted roles in the tumor microenvironment beyond their structural functions, particularly in hepatocellular carcinoma (HCC). This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC, including their involvement in angiogenesis, immune modulation, lymphangiogenesis, and metastasis. By providing a detailed account of the complex interplay between LECs, BECs, and tumor cells, this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.

6.
J Proteome Res ; 23(6): 2054-2066, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38775738

RESUMO

The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.


Assuntos
Neoplasias Colorretais , Lipidômica , Fosfatidiletanolaminas , Espectrometria de Massas em Tandem , Língua , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , Lipidômica/métodos , Masculino , Feminino , Língua/microbiologia , Língua/metabolismo , Língua/patologia , Língua/química , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Fosfatidiletanolaminas/metabolismo , Fosfatidiletanolaminas/análise , Idoso , Cromatografia Líquida , Lipídeos/análise , Lipídeos/química , Triglicerídeos/metabolismo , Triglicerídeos/análise , Adenoma/metabolismo , Adenoma/microbiologia , Esfingomielinas/análise , Esfingomielinas/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/química , Plasmalogênios/análise , Plasmalogênios/metabolismo , Plasmalogênios/química , Estudos de Casos e Controles , Etanolaminas/metabolismo , Etanolaminas/análise , Etanolaminas/química , Ceramidas/metabolismo , Ceramidas/análise , Adulto
7.
Anal Chem ; 96(19): 7747-7755, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38691774

RESUMO

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTDAND-AND) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTDOR-AND) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTDAND-AND and MTDOR-AND, while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.


Assuntos
DNA , Molécula de Adesão da Célula Epitelial , MicroRNAs , Humanos , Molécula de Adesão da Célula Epitelial/metabolismo , DNA/química , MicroRNAs/análise , MicroRNAs/metabolismo , Mucina-1/metabolismo , Mucina-1/análise , Computadores Moleculares , Células MCF-7 , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Membrana Celular/metabolismo , Membrana Celular/química , Células Hep G2
8.
Int J Surg ; 110(3): 1755-1769, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38484261

RESUMO

BACKGROUND: The gradual evolution of the detection and quantification of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this study was to assess the diagnostic potential of exhaled breath and urinary VOCs in cancer detection. As VOCs are indicative of tumor and human metabolism, our work also sought to investigate the metabolic pathways linked to the development of cancerous tumors. MATERIALS AND METHODS: An electronic search was performed in the PubMed database. Original studies on VOCs within exhaled breath and urine for cancer detection with a control group were included. A meta-analysis was conducted using a bivariate model to assess the sensitivity and specificity of the VOCs for cancer detection. Fagan's nomogram was designed to leverage the findings from our diagnostic analysis for the purpose of estimating the likelihood of cancer in patients. Ultimately, MetOrigin was employed to conduct an analysis of the metabolic pathways associated with VOCs in relation to both human and/or microbiota. RESULTS: The pooled sensitivity, specificity and the area under the curve for cancer screening utilizing exhaled breath and urinary VOCs were determined to be 0.89, 0.88, and 0.95, respectively. A pretest probability of 51% can be considered as the threshold for diagnosing cancers with VOCs. As the estimated pretest probability of cancer exceeds 51%, it becomes more appropriate to emphasize the 'ruling in' approach. Conversely, when the estimated pretest probability of cancer falls below 51%, it is more suitable to emphasize the 'ruling out' approach. A total of 14, 14, 6, and 7 microbiota-related VOCs were identified in relation to lung, colorectal, breast, and liver cancers, respectively. The enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in the aforementioned tumor types. CONCLUSIONS: The analysis of exhaled breath and urinary VOCs showed promise for cancer screening. In addition, the enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in four tumor types, namely lung, colorectum, breast and liver. These findings hold significant implications for the prospective clinical application of multiomics correlation in disease management and the exploration of potential therapeutic targets.


Assuntos
Testes Respiratórios , Neoplasias , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/urina , Neoplasias/diagnóstico , Redes e Vias Metabólicas , Expiração
9.
Redox Biol ; 71: 103118, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38490069

RESUMO

The induction of ferroptosis is promising for cancer therapy. However, the mechanisms enabling cancer cells to evade ferroptosis, particularly in low-cystine environments, remain elusive. Our study delves into the intricate regulatory mechanisms of Activating transcription factor 3 (ATF3) on Cystathionine ß-synthase (CBS) under cystine deprivation stress, conferring resistance to ferroptosis in colorectal cancer (CRC) cells. Additionally, our findings establish a positively correlation between this signaling axis and CRC progression, suggesting its potential as a therapeutic target. Mechanistically, ATF3 positively regulates CBS to resist ferroptosis under cystine deprivation stress. In contrast, the suppression of CBS sensitizes CRC cells to ferroptosis through targeting the mitochondrial tricarboxylic acid (TCA) cycle. Notably, our study highlights that the ATF3-CBS signaling axis enhances ferroptosis-based CRC cancer therapy. Collectively, the findings reveal that the ATF3-CBS signaling axis is the primary feedback pathway in ferroptosis, and blocking this axis could be a potential therapeutic approach for colorectal cancer.


Assuntos
Neoplasias Colorretais , Ferroptose , Humanos , Cistationina beta-Sintase/metabolismo , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Ferroptose/genética , Cistina , Carcinogênese/genética , Transformação Celular Neoplásica , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo
12.
J Biomater Appl ; 38(7): 858-865, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38165217

RESUMO

The objective of this study is to clarify whether the omental coating can effectively attenuate foreign body reaction (FBR) induced by implanted materials. Male Sprague-Dawley rats were injected with polydextran particle slurry intraperitoneally to activate the omentum. 7 days later, polyether polyurethane sponge discs were implanted subcutaneously on each side of the rat's back as the foreign implants to induce FBR. The next day, omental transposition were performed. The disc on the left side of each rat's back was wrapped with omental flap (omental group); the disc on the right side was untreated (control group). All discs were removed 21 days after implantation and assessed by determining the components of the fibrovascular tissue (angiogenesis, inflammation, foreign body giant cells (FBGCs) aggregation and fibrogenesis). In implants in omental group, micro vessel density (MVD), Hemoglobin (Hb) content and VEGF levels (pro-angiogenic cytokine) were increased when compared with implants from control group. Inflammatory parameters (IL-1ß; macrophage accumulation-NAG activity; neutrophil accumulation- MPO levels) were decreased in implants after omental coating. Also, collagen deposition, fibrous capsule thickness, and FBGCs decreased in implants from omental group. However, intra-implant levels of TNF-α and TGF-ß1 were not different after omental coating. Our findings showed for the first time that the omental coating around the implants attenuate the adverse FBR, it may be critical in developing new strategies to control FBR and improve the function and performance of the implanted materials.


Assuntos
Omento , Fator A de Crescimento do Endotélio Vascular , Ratos , Masculino , Animais , Omento/cirurgia , Ratos Sprague-Dawley , Reação a Corpo Estranho/etiologia , Inflamação/etiologia
13.
Mol Cancer Ther ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37963566

RESUMO

Aberrant N-linked glycosylation is a prominent feature of cancers. Perturbance of oligosaccharide structure on cell surfaces directly affects key processes in tumor development and progression. In spite of the critical role played by N-linked glycans in tumor biology, the discovery of small molecules that specifically disturbs the N-linked glycans is still under investigation. To identify more saccharide-structure-perturbing compounds, a repurposed drug screen by using a library consisting of 1530 FDA-approved drugs was performed. Interestingly, an antipsychotic drug, penfluridol, was identified as being able to decrease cell surface Wheat germ agglutinin (WGA) staining. In the presence of penfluridol, cell membrane glycoproteins PD-L1 shifted to a lower molecular weight. Further studies demonstrated that penfluridol treatment caused an accumulation of high-mannose oligosaccharides, especially Man5-7GlcNAc2 glycan structures. Mechanistically, this effect is due to direct targeting of MAN1A1 mannosidase, a Golgi enzyme involved in N-glycan maturation. Moreover, we found that altered glycosylation of PD-L1 caused by penfluridol disrupted interactions between PD-1 and PD-L1, resulting in activation of T-cell tumor immunity. In a mouse xenograft and glioma model, penfluridol enhanced the anti-tumor effect of the anti-PD-L1 antibody in vivo. Overall, these findings revealed an important biological activity of the antipsychotic drug penfluridol as an inhibitor of glycan processing and proposed a repurposed use of penfluridol in anti-tumor therapy through activation of T-cell immunity.

14.
Biol Proced Online ; 25(1): 29, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37953280

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes. METHODS: Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes. RESULTS: Our study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients. CONCLUSIONS: These findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.

15.
Hortic Res ; 10(4): uhad022, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37786859

RESUMO

Flower senescence is commonly enhanced by the endogenous hormone ethylene and suppressed by the gibberellins (GAs) in plants. However, the detailed mechanisms for the antagonism of these hormones during flower senescence remain elusive. In this study, we characterized one up-regulated gene PhOBF1, belonging to the basic leucine zipper transcription factor family, in senescing petals of petunia (Petunia hybrida). Exogenous treatments with ethylene and GA3 provoked a dramatic increase in PhOBF1 transcripts. Compared with wild-type plants, PhOBF1-RNAi transgenic petunia plants exhibited shortened flower longevity, while overexpression of PhOBF1 resulted in delayed flower senescence. Transcript abundances of two senescence-related genes PhSAG12 and PhSAG29 were higher in PhOBF1-silenced plants but lower in PhOBF1-overexpressing plants. Silencing and overexpression of PhOBF1 affected expression levels of a few genes involved in the GA biosynthesis and signaling pathways, as well as accumulation levels of bioactive GAs GA1 and GA3. Application of GA3 restored the accelerated petal senescence to normal levels in PhOBF1-RNAi transgenic petunia lines, and reduced ethylene release and transcription of three ethylene biosynthetic genes PhACO1, PhACS1, and PhACS2. Moreover, PhOBF1 was observed to specifically bind to the PhGA20ox3 promoter containing a G-box motif. Transient silencing of PhGA20ox3 in petunia plants through tobacco rattle virus-based virus-induced gene silencing method led to accelerated corolla senescence. Our results suggest that PhOBF1 functions as a negative regulator of ethylene-mediated flower senescence by modulating the GA production.

16.
BMC Urol ; 23(1): 161, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828507

RESUMO

BACKGROUND: To summarize the efficacy of combined robot-assisted laparoscopy and ureteroscopy in treating complex ureteral strictures. METHODS: Eleven patients underwent combined robot-assisted laparoscopy and ureteroscopy for ureteral strictures between January 2020 and August 2022. Preoperative B-ultrasound, glomerular filtration rate measurement, and intravenous pyelography showed different degrees of hydronephrosis in the affected kidney and moderate to severe stenosis in the corresponding part of the ureter. During the operation, stricture segment resection and end-to-end anastomosis were performed using the da Vinci robot to find the stricture point under the guidance of a ureteroscopic light source in the lateral or supine lithotomy position. RESULTS: All the patients underwent robot-assisted laparoscopy and ureteroscopy combined with end-to-end ureterostenosis. There were no conversions to open surgery or intraoperative complications. Significant ureteral stricture segments were found in all patients intraoperatively; however, stricture length was not significantly different from the imaging findings. Patients were followed up for 3-27 months. Two months postoperatively, the double-J stent was removed, a ureteroscopy was performed, the ureteral mucosa at the end-to-end anastomosis grew well, and the lumen was patent in all patients. Furthermore, imaging examination showed that hydronephrosis was significantly improved in all patients, with grade I hydronephrosis in three cases and grade 0 hydronephrosis in eight cases. No recurrence of ureteral stricture was observed in patients followed up for > 1 year. CONCLUSION: Robot-assisted laparoscopy combined with ureteroscopy is an effective method for treating complex ureteral strictures and can achieve accurate localization of the structured segment.


Assuntos
Hidronefrose , Laparoscopia , Robótica , Ureter , Obstrução Ureteral , Humanos , Ureteroscopia/métodos , Constrição Patológica/cirurgia , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/cirurgia , Ureter/cirurgia , Laparoscopia/métodos , Hidronefrose/cirurgia , Hidronefrose/complicações , Estudos Retrospectivos
17.
Analyst ; 148(20): 4967-4981, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37724375

RESUMO

A malignant tumour has hypoxic cells of varying degrees. The more severe the hypoxic degree, the more difficult the prognosis of the tumour and the higher the recurrence rate. Therefore, tumour hypoxia imaging is crucial. Magnetic resonance imaging (MRI) shows its strength in high resolution, depth of penetration and noninvasiveness. However, it needs more excellent contrast agents (CAs) to combat the complex tumour microenvironment (TME) and increased targeting of tumours to enhance clinical safety. Many research studies have focused on developing hypoxia-responsive MRI CAs that take advantage of the unique characteristics of hypoxic tumours. The low oxygen pressure, acidic TME, and up-regulated redox molecule levels found in hypoxic tumours serve as biological stimuli for nanoformulations that can accurately image the hypoxic region. This review highlights the importance of developing bioparameter-directed nanoformulations as MRI CAs for accurate tumour diagnosis. The design strategies and mechanisms of tumour-hypoxia imaging with nanoformulations are exemplified, with a focus on pH-responsiveness, redox-responsiveness, and p(O2)-responsiveness. The promising future of bioparameter-responsive nanoformulations for accurate tumour diagnosis and personalised cancer treatment is discussed.

18.
Exp Hematol Oncol ; 12(1): 66, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37501090

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era.

19.
Ann Hematol ; 102(10): 2933-2942, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37421505

RESUMO

Rhino-orbital-cerebral mucormycosis (ROCM), which is an acute fatal infectious disease with a high mortality rate, is increasingly being diagnosed in patients with hematological diseases worldwide. We aimed to investigate the clinical characteristics, treatment, and prognosis of hematological diseases complicated by ROCM. Our sample comprised a total of 60 ROCM patients with hematological diseases. The most common primary disease was acute lymphoblastic leukemia (ALL) (n=27, 45.0%), while 36 patients (60.0%) were diagnosed with a clear type of pathogen, all belonging to the Mucorales, most commonly Rhizopus (41.7%). Of the 32 patients (53.3%) who died, 19 (59.3%) died of mucormycosis, and 84.2% (n=16) of those died within 1 month. Forty-eight cases (80.0%) received antifungal treatment combined with surgical therapy, 12 of whom (25.0%) died of mucormycosis, amounting to a mortality rate that was significantly lower than in patients who received antifungal therapy alone (n=7, 58.3%) (P=0.012). The median neutrophil value of patients who underwent surgery was 0.58 (0.11-2.80) 103/µL, the median platelet value was 58.00 (17.00-93.00) 103/µL, and no surgery-related deaths were reported. Multivariate analysis showed that patient's advanced age (P=0.012, OR=1.035 (1.008-1.064)) and lack of surgical treatment (P=0.030, OR=4.971 (1.173-21.074)) were independent prognostic factors.In this study, hematological diseases associated with ROCM have a high mortality rate. Lack of surgical treatment is an independent prognostic factor for death from mucormycosis. Surgery may therefore be considered in patients with hematological disease even if their neutrophil and platelet values are lower than normal.


Assuntos
Doenças Hematológicas , Mucorales , Mucormicose , Humanos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Antifúngicos/uso terapêutico , Desbridamento , Doenças Hematológicas/complicações , Doenças Hematológicas/tratamento farmacológico
20.
BMC Musculoskelet Disord ; 24(1): 571, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37442968

RESUMO

BACKGROUND: The triglyceride glucose (TyG) index, an indicator of insulin resistance, is often associated with adverse outcomes in various cardiovascular diseases, while hypertension is associated with an increased risk of cardiovascular diseases. As the loss of muscle mass in people with hypertension is poorly understood, the current study aimed to explore the relationship between TyG index and muscle mass in hypertensive population. METHODS: We analyzed data from hypertensive adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. The TyG index and body mass index (BMI)-adjusted skeletal muscle mass index (SMI) were calculated and the relationship between the two was evaluated using multivariable linear regression and restricted cubic spline (RCS) regression models. RESULTS: A total of 1633 participants in the dataset were included for the final analysis. In the multivariable regression analysis, the adjusted ß of SMI with a 95% confidence interval (CI) for the highest TyG index quartile was - 5.27 (- 9.79 to - 0.75), compared with the lowest quartile. A negative linear relationship between TyG index and SMI was plotted by RCS regression (nonlinear P = 0.128). Stratified models of non-smoking women of different ages also demonstrated that SMI decreased as TyG index increased (all P for trend < 0.05). CONCLUSION: This linear and negative correlation between TyG index and SMI in hypertensive patients suggests that insulin resistance adversely affects muscle mass.


Assuntos
Doenças Cardiovasculares , Hipertensão , Resistência à Insulina , Humanos , Adulto , Feminino , Índice de Massa Corporal , Inquéritos Nutricionais , Hipertensão/epidemiologia , Glucose , Triglicerídeos , Músculo Esquelético , Glicemia , Biomarcadores , Fatores de Risco
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