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1.
Org Lett ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578703

RESUMO

Here, we present the straightforward synthesis of N-fluorosulfonyl guanidine (1) from two industrial feedstocks, guanidine hydrochloride and sulfuryl fluoride (SO2F2), using SuFEx chemistry. Compound 1 exhibits excellent stability under ambient conditions and displays unique SuFEx reactivity toward amines and phenols to generate N-guanyl sulfamides and sulfamates that have rarely been accessed. Notably, water serves as an effective solvent in this process. Our protocol provides a reliable pathway for the synthesis and investigation of these novel guanidine-containing molecules.

2.
Chin Neurosurg J ; 10(1): 12, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594757

RESUMO

BACKGROUND: Patients with disorders of consciousness (DoC) exhibit varied revival outcomes based on different etiologies and diagnoses, the mechanisms of which remain largely unknown. The fluctuating clinical presentations in DoC pose challenges in accurately assessing consciousness levels and prognoses, often leading to misdiagnoses. There is an urgent need for a deeper understanding of the physiological changes in DoC and the development of objective diagnostic and prognostic biomarkers to improve treatment guidance. METHODS: To explore biomarkers and understand the biological processes, we conducted a comprehensive untargeted metabolomic analysis on serum samples from 48 patients with DoC. Patients were categorized based on etiology (TBI vs. non-TBI), CRS-R scores, and prognosis. Advanced analytical techniques, including PCA and OPLS-DA models, were employed to identify differential metabolites. RESULTS: Our analysis revealed a distinct separation in metabolomic profiles among the different groups. The primary differential metabolites distinguishing patients with varying etiologies were predominantly phospholipids, with a notable decrease in glycerophospholipids observed in the TBI group. Patients with higher CRS-R scores exhibited a pattern of impaired carbohydrate metabolism coupled with enhanced lipid metabolism. Notably, serum concentrations of both LysoPE and PE were reduced in patients with improved outcomes, suggesting their potential as prognostic biomarkers. CONCLUSIONS: Our study underscores the critical role of phospholipid metabolism in the brain's metabolic alterations in patients with DoC. It identifies key biomarkers for diagnosis and prognosis, offering insights that could lead to novel therapeutic targets. These findings highlight the value of metabolomic profiling in understanding and potentially treating DoC.

3.
Bioinformatics ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561176

RESUMO

MOTIVATION: Understanding the intermolecular interactions of ligand-target pairs is key to guiding the optimization of drug research on cancers, which can greatly mitigate overburden workloads for wet labs. Several improved computational methods have been introduced and exhibit promising performance for these identification tasks, but some pitfalls restrict their practical applications. (i)First, existing methods do not sufficiently consider how multigranular molecule representations influence interaction patterns between proteins and compounds. (ii)Second, existing methods seldom explicitly model the binding sites when an interaction occurs to enable better prediction and interpretation, which may lead to unexpected obstacles to biological researchers. RESULTS: To address these issues, we here present DrugMGR, a deep multigranular drug representation model capable of predicting binding affinities and regions for each ligand-target pair. We conduct consistent experiments on three benchmark datasets using existing methods and introduce a new specific dataset to better validate the prediction of binding sites. For practical application, target-specific compound identification tasks is also carried out to validate the capability of real-world compound screen. Moreover, the visualization of some practical interaction scenarios provides interpretable insights from the results of the predictions. The proposed DrugMGR achieves excellent overall performance in these datasets, exhibiting its advantages and merits against state-of-the-art methods. Thus, the downstream task of DrugMGR can be fine-tuned for identifying the potential compounds that target proteins for clinical treatment. AVAILABILITY: https://github.com/lixiaokun2020/DrugMGR. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

4.
Cancer Manag Res ; 16: 177-183, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525374

RESUMO

Objective: Cystic brain metastases (BMs) are rare in small cell lung cancer (SCLC), and there are limited data on the treatment and prognosis of cystic BMs. Whole brain radiotherapy has been the mainstay for BMs since several years. Immune checkpoint inhibitors in extensive stage small cell lung cancer (ES-SCLC) have been shown to be suitable for patients who experienced better overall survival and progress-free survival and have been approved as the first-line treatment for ES-SCLC. In this report, we described two ES-SCLC patients developed cystic BMs after immunotherapy, after which the patients continued to treat the primary lesion with immune checkpoint inhibitors and the cystic BMs with radiotherapy. Case Description: Two male patients were diagnosed with ES-SCLC at the first admission and were subsequently treated with immunotherapy plus platinum therapy, during which cystic BMs developed. One patient received whole brain radiotherapy and the other received whole brain radiotherapy and Gamma knife radiosurgery (GKRS). Immunotherapy was continued after the brain lesions were controlled. It has been 33 months since the first patient was diagnosed and is now in stable condition. The other patient achieved an overall survival of 30 months. Conclusion: This report describes two patients with cystic brain metastases in ES-SCLC. Whole brain radiotherapy has a good effect on local control of cystic brain metastases in small cell lung cancer and can significantly improve the symptoms of patients. At the same time, we treat immunotherapy as the first-line treatment, and then perform cross-immunotherapy after disease progression, combined with anti-vascular targeting drugs. The patient did not develop severe iRAEs.

5.
Cancer Lett ; 588: 216760, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38428724

RESUMO

Oncolytic viruses have emerged as a promising modality for cancer treatment due to their unique abilities to directly destroy tumor cells and modulate the tumor microenvironment. Bispecific T-cell engagers (BsAbs) have been developed to activate and redirect cytotoxic T lymphocytes, enhancing the antitumor response. To take advantage of the specific infection capacity and carrying ability of exogenous genes, we generated a recombinant herpes simplex virus type 1 (HSV-1), HSV-1dko-B7H3nb/CD3 or HSV-1dko-B7H3nb/mCD3, carrying a B7H3nb/CD3 or B7H3nb/mCD3 BsAb that replicates and expresses BsAb in tumor cells in vitro and in vivo. The new generation of oncolytic viruses has been genetically modified using CRISPR/Cas9 technology and the cre-loxp system to increase the efficiency of HSV genome editing. Additionally, we used two fully immunocompetent models (GL261 and MC38) to assess the antitumor effect of HSV-1dko-B7H3nb/mCD3. Compared with the HSV-1dko control virus, HSV-1dko-B7H3nb/mCD3 induced enhanced anti-tumor immune responses and T-cell infiltration in both GL261 and MC38 models, resulting in improved treatment efficacy in the latter. Furthermore, flow cytometry analysis of the tumor microenvironment confirmed an increase in NK cells and effector CD8+ T cells, and a decrease in immunosuppressive cells, including FOXP3+ regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and CD206+ macrophages (M2). Overall, our study identified a novel camel B7H3 nanobody and described the genetic modification of the HSV-1 genome using CRISPR/Cas9 technology and the cre-loxp system. Our findings indicate that expressing B7H3nb/CD3 BsAb could improve the antitumor effects of HSV-1 based oncolytic virus.


Assuntos
Herpesvirus Humano 1 , Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Herpesvirus Humano 1/genética , Linfócitos T CD8-Positivos , Vírus Oncolíticos/genética , Neoplasias/genética , Terapia Viral Oncolítica/métodos , Microambiente Tumoral
6.
Ann Thorac Surg ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38499219

RESUMO

BACKGROUND: We aimed to validate the prognostic implication of uncertain resection, R(un), proposed by International Association for the Study of Lung Cancer (IASLC) and evaluate the prognostic value of spread through air spaces (STAS) in reclassifying the R classification among patients with lung adenocarcinoma after segmentectomy. METHODS: We enrolled 1007 patients who underwent segmentectomy for c-stage IA lung adenocarcinoma between 2014 and 2017. Recurrence-free survival (RFS) and overall survival (OS) were compared to evaluate the prognostic value of IASLC-R(un) and STAS. Whether STAS would skip into complementary lobectomy was evaluated in a prospective cohort. RESULTS: The current IASLC-R(un) failed to significantly stratify the RFS (P = .078) in segmentectomy, and STAS was a stronger risk factor of poor prognosis for both RFS and OS (P < .001). Moreover, the presence of STAS was associated with increased locoregional recurrence in patients undergoing segmentectomy (P < .001) but not in those treated with lobectomy (P = .187), indicating that only STAS-positive segmentectomy was consistent with the concept of R(un) in relapse pattern. After reclassifying STAS-positive segmentectomy into the R(un) category, the proposed R(un) showed an improvement in prognosis stratification. In addition, 2 of 30 patients (6.2%) in the prospective cohort who underwent initial segmentectomy and complementary lobectomy had STAS clusters in the complementary lobectomy specimens. CONCLUSIONS: Unfavorable prognosis, relapse patterns consistent with R(un), and pathologic verification that saltatory spread of STAS observed in complementary lobectomy specimens supported reclassifying STAS-positive segmentectomy as R(un). STAS is a critical concern for the surgical completeness evaluation after segmentectomy.

7.
Microorganisms ; 12(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38543609

RESUMO

Many epidemics are caused by negative-stranded RNA viruses, leading to serious disease outbreaks that threaten human life and health. These viruses also have a significant impact on animal husbandry, resulting in substantial economic losses and jeopardizing global food security and the sustainable livelihoods of farmers. However, the pathogenic and infection mechanism of most negative-stranded RNA viruses remain unclear. Reverse genetics systems are the most powerful tools for studying viral protein function, viral gene expression regulation, viral pathogenesis, and the generation of engineered vaccines. The reverse genetics of some negative-strand viruses have been successfully constructed, while others have not. In this review, we focus on representative viruses from the Orthomyxoviridae family (IAV), the Filoviridae family (EBOV), and the Paramyxoviridae family (PPRV) to compile and summarize the existing knowledge on reverse genetics techniques for negative-strand viruses. This will provide a theoretical foundation for developing reverse genetics techniques for some negative-strand viruses.

8.
Virology ; 595: 110056, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38552409

RESUMO

The Peste des petits ruminant virus (PPRV) is a member of the Paramyxoviridae family and is classified into the genus Measles virus. PPRV predominantly infects small ruminants, leading to mortality rates of nearly 100%, which have caused significant economic losses in developing countries. Host proteins are important in virus replication, but the PPRV nucleocapsid (N) protein-host interacting partners for regulating PPRV replication remain unclear. The present study confirmed the interaction between PPRV-N and the host protein vimentin by co-immunoprecipitation and co-localization experiments. Overexpression of vimentin suppressed PPRV replication, whereas vimentin knockdown had the opposite effect. Mechanistically, N was subjected to degradation via the ubiquitin/proteasome pathway, where vimentin recruits the E3 ubiquitin ligase NEDD4L to fulfill N-ubiquitination, resulting in the degradation of the N protein. These findings suggest that the host protein vimentin and E3 ubiquitin ligase NEDD4L have an anti-PPRV effect.

9.
Nat Prod Res ; : 1-4, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38403948

RESUMO

This study used network pharmacology and molecular docking techniques to investigate the molecular targets and pathways of Danggui Buxue Tang (DBT) in treating lung cancer. The compound-target network was constructed using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and a lung cancer-specific network was created using the GEO database and Cytoscape software. GO and KEGG pathway analyses were performed to understand the biological processes associated with DBT. The key compounds from Astragalus, kaempferol, and quercetin, and the potential targets are IL-6, IL-1ß, FOS, ICAM1, and CCL2. GO enrichment analysis revealed numerous biological process-related entries, while KEGG pathway analysis highlighted the TNF and IL-17 signalling pathways. Molecular docking confirmed the stable binding activity between the main active compounds of DBT and the target proteins. Overall, these findings shed light on the molecular mechanism of DBT in treating lung cancer, providing insights into targets, pathways, and biological processes involved.

10.
Lung Cancer ; 189: 107472, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38320371

RESUMO

OBJECTIVES: The Lepidic Component (LP) identifies a subgroup with an excellent prognosis for lung adenocarcinoma (LUAD). Our research aimed to propose an improved pathological T (pT) stage for LUAD based on LP. MATERIALS AND METHODS: Totally, 3335 surgical patients with pathological stage I LUAD were incorporated. Factors affecting survival were investigated by analyzing recurrence-free survival (RFS) and overall survival (OS) using the Kaplan-Meier method and Cox regression analyses. Subgroup analysis based on Lepidic Ratio (LR) was further evaluated. The net benefit from the modified pT category (pTm) was assessed using the Area Under the time-dependent Receiver Operating Curve (AUC), Harrell's Concordance Index (C-index), Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). RESULTS: The presence of LP (LP+) was identified in 1425 (42.7 %) patients, indicating a significantly better RFS (P < 0.001) and OS (P < 0.001) than those without LP, and similar results were reproduced in pT1a-pT2a subcategory (P < 0.050 for all). Multivariable Cox analysis revealed LP+ as an independent prognostic factor for both RFS (HR, 0.622; P < 0.001) and OS (HR, 0.710; P = 0.019). However, lepidic ratio (LR) was not independently associated with both RFS and OS for LP+ patients. The 5-year RFS and OS rates between T1a (LP-) and T1b (LP+), T1b (LP-) and T1c (LP+), and T1b (LP-) and T2a (LP+) were comparable (P > 0.050 for all). After modification, compared with current 8th edition pT stage system (pT8), pTm independently predicted RFS and OS, and AUCs, c-index, NRI, and IDI analysis all demonstrated pTm holds better discrimination performances than pT8 for LUAD prognosis. CONCLUSION: LP can be an additional down-staged T descriptor for pathological stage I LUAD and improve the survival predictive performance of reclassification.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Área Sob a Curva
11.
J Pain Res ; 17: 381-392, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312505

RESUMO

Objective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients. Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3). Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = -10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = -0.13, sig < 0.05). Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.

12.
Insects ; 15(2)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38392538

RESUMO

Predatory mites are biological control agents used in many countries against various vegetable pests, particularly spider mites. Despite the significant presence of predatory mites in the Tibetan plateau, there is limited research on their potential against spider mites in the area. This study investigated the fitness parameters and performance against TSSM of four predatory, including Amblyseius swirskii (Athias-Henriot) and three species from the genus Neoseiulus (Neoseiulus californicus (McGregor), Neoseiulus barkeri (Hughes), and Neoseiulus cucumeris (Oudemans)), originally collected from fields in the Tibetan Plateau. Compared to the other three predatory species, A. swirskii exhibited the highest fecundity (11.60 ± 0.34) and the highest pre-adult survival rate (83.33 ± 3.33%). Since their juvenile survival rate (SR) was extremely low (13.33% ± 5.77%), most N. barkeri nymphs died before emergence. Compared to the other three predatory mites, A. swirskii showed the highest predation capacity against adult TSSMs at 15 d post-release (14.28 ± 2.24). Based on the results, A. swirskii was the most effective, and N. barkeri was the least effective in controlling two-spotted mites in the Tibetan Plateau among the four species tested in this study. Collectively, these findings imply notable advantages in employing A. swirskii for controlling two-spotted mites in the Tibetan Plateau. This study informs the development of a feasible biological control method based on suitable predatory mite species to manage TSSMs in the Tibetan Plateau.

13.
J Gene Med ; 26(1): e3658, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282149

RESUMO

BACKGROUND: Aberrant activation of the phosphatidlinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway has been shown to play an important role in lung adenocarcinoma (LUAD). The effect of KRAS mutations, one of the important signatures of LUAD, on the PI3K/AKT/mTOR pathway in LUAD remains unclear. METHODS: The Seurat package and principal component analysis were used for cell categorization of single-cell RNA sequencing data of LUAD. The AUCell score was used to assess the activity of the PI3K/AKT/mTOR pathway. Meanwhile, using the gene expression profiles and mutation profiles in the The Cancer Genome Atlas dataset, LUAD patients were categorized into KRAS-mutant (KRAS-MT) and KRAS-wild-types (KRAS-WT), and the corresponding enrichment scores were calculated using gene set enrichment analysis analysis. Finally, the subpopulation of cells with the highest pathway activity was identified, the copy number variation profile of this subpopulation was inscribed using the inferCNV package and the CMap database was utilized to make predictions for drugs targeting this subpopulation. RESULTS: There is higher PI3K/AKT/mTOR pathway activity in LUAD epithelial cells with KRAS mutations, and high expression of KRAS, PIK3CA, AKT1 and PDPK1. In particular, we found significantly higher levels of pathway activity and associated gene expression in KRAS-MT than in KRAS-WT. We identified the highest pathway activity on a subpopulation of GRB2+ epithelial cells and the presence of amplified genes within its pathway. Finally, drugs were able to target GRB2+ epithelial cell subpopulations, such as wortmannin, palbociclib and angiogenesis inhibitor. CONCLUSIONS: The present study provides a basic theory for the activation of the PI3K/AKT/mTOR signaling pathway as a result of KRAS mutations.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/genética , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Adenocarcinoma de Pulmão/genética , Variações do Número de Cópias de DNA , Neoplasias Pulmonares/patologia , Mutação , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Análise de Sequência de RNA , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
14.
Appl Opt ; 63(2): 429-436, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38227239

RESUMO

Two-sided coated optical lenses are important in optical applications. A film-stress-induced aberration can adversely affect the lens performance. In this paper, a mechanical method has been developed to reduce this aberration. The proposed method uses a specialized finite element method with an easy modeling process and high versatility to analyze the impact of film parameters (including stress, the thickness, and the coating range) on aberrations under different lens geometric parameters. Theoretically, by selecting the property film parameters within the range of an application's requirements can reduce the aberrations. The proposed method could reduce film-stress-induced aberrations to make the aberration compensation easier.

15.
Nanoscale ; 16(5): 2662-2671, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230765

RESUMO

Materials exhibiting X-ray-induced photochromism have consistently piqued the interest of researchers. Exploring the photochromic properties of such materials is valuable for understanding the structural changes and electron transfer processes that occur under high energy radiation, such as X-ray irradiation. Here, a crystalline silver(I) nanocluster synthesized from tert-butylacetylene silver was found to have the ability to exhibit color and photoluminescence changes upon exposure to X-ray radiation. The responsive behavior was observed across a wide temperature range of 100-300 K, with the ability to respond particularly well to soft X-rays (λ > 1 Å) and exhibit light responsiveness to hard X-rays (λ < 1 Å). By combining experimental findings including X-ray diffraction, X-ray photoelectron spectroscopy, electron spin resonance, etc. with theoretical calculations, we have proposed that X-ray irradiation induces electron transfer from chloride (Cl-) located in the center of the silver(I) nanocluster to the surrounding Ag14 in the skeleton. This represents the first documented example in which electron transfer induced by X-ray excitation has been observed, accompanied by a photochromism process, in silver nanoclusters. This study contributes to our understanding of X-ray-induced photochromism and the electron transfer process in silver cluster compounds. It also provides valuable insights and potential design strategies for applications such as photochromism, photoluminescence color change, and photoenergy conversion.

16.
Phytomedicine ; 124: 155255, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181528

RESUMO

BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.


Assuntos
Artrite Experimental , Artrite Reumatoide , Berberina , MicroRNAs , Animais , Camundongos , Ratos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Berberina/farmacologia , Linfócitos T CD4-Positivos , Modelos Animais de Doenças , Macrófagos , MicroRNAs/metabolismo
17.
Bioresour Technol ; 395: 130381, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281545

RESUMO

Biogas production via anaerobic digestion is highly attractive for microalgae. The technology of microalgae cultivation has profound impacts on biogas production system as it is the most energy-consuming process. However, a comprehensive evaluation of the environmental and economic benefits of different cultivation systems has yet to be sufficiently conducted. Here, life-cycle and economic assessments of open raceway ponds, photobioreactors and biofilm systems were investigated. Results showed greenhouse gas emissions of all systems were positive because more than two-thirds of carbon in fuel gas was lost and the fixed carbon in product gas and solid fertilizer was less than the emitted carbon during energy input. Particularly, biofilm system achieved the least greenhouse gas emissions (9.3 g CO2-eq/MJ), net energy ratio (0.7) and levelized cost of energy (0.9 $/kWh), indicating the optimum cultivation system. Open raceway ponds and photobioreactors failed to achieve positive benefits because of low harvesting efficiency and biomass concentration.


Assuntos
Gases de Efeito Estufa , Microalgas , Biocombustíveis/análise , Dióxido de Carbono/análise , Biomassa , Biofilmes , Carbono
18.
CNS Neurosci Ther ; 30(2): e14388, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37563991

RESUMO

OBJECTIVES: This study investigated the prognostic effect of electroencephalography (EEG) instant effects of single spinal cord stimulation (SCS) on clinical outcome in disorders of consciousness (DOC) and the time-dependent brain response during the recovery of consciousness prompted by SCS. METHODS: Twenty three patients with DOC underwent short-term SCS (stSCS) implantation operation. Then, all patients received the postoperative EEG test including EEG record before (T1) and after (T2) single SCS session. Subsequently, 2 weeks stSCS treatment was performed and revised coma recovery scale (CRS-R) and EEG data were collected. Finally, they were classified into effective and ineffective groups at 3-month follow-up (T6). RESULTS: The parietal-occipital (PO) connectivity and clustering coefficients (CC) in the beta band of the effective group at the 1 week after the treatment (T5) were found to be higher than preoperative assessment (T0). Correlation analysis showed that the change in beta CC at T1/T2 was correlated with the change in CRS-R at T0/T6. In addition, the change in PO connectivity and CC in the beta at T0/T5 were also correlated with the change in CRS-R at T0/T5. CONCLUSION: SCS may facilitate the recovery of consciousness by enhancing local information interaction in posterior brain regions. And the recovery can be predicted by beta CC in the EEG test.


Assuntos
Estimulação da Medula Espinal , Humanos , Transtornos da Consciência/terapia , Eletroencefalografia , Encéfalo , Prognóstico , Estado de Consciência
19.
Apoptosis ; 29(3-4): 331-343, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37848671

RESUMO

Tumor immune escape is an important manner for colon cancer to escape effective killing by immune system. Currently, the immune checkpoint PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy in colon cancer. Here, present work aims to investigate the biological function of N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in regulating colon cancer's immune escape and CD8 + T cells-mediated tumor cytotoxicity and apoptosis. Results illustrated that IGF2BP1 was closely correlated to the colon cancer patients' poor clinical outcome. Functionally, upregulation of IGF2BP1 suppressed the CD8+ T-cells mediated antitumor immunity through reducing their tumor cytotoxicity. Mechanistically, MeRIP-Seq revealed that programmed death ligand 1 (PD-L1) mRNA had a remarkable m6A modified site on 3'-UTR genomic. Moreover, PD-L1 acted as the target of IGF2BP1, which enhanced the stability of PD-L1 mRNA. Overall, these results indicated that IGF2BP1 targeted PD-L1 to accelerate the immune escape in colon cancer by reducing CD8 + T cells-mediated tumor cytotoxicity in m6A-dependent manner. The findings demonstrate the potential of m6A-targeted immune checkpoint blockade in colon cancer, providing a novel insight for colon cancer immune escape and antitumor immunity in further precise treatment.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias do Colo , Humanos , Linfócitos T CD8-Positivos/metabolismo , Antígeno B7-H1/genética , Apoptose/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , RNA Mensageiro/metabolismo
20.
Environ Toxicol ; 39(1): 289-298, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37705237

RESUMO

We have previously found that a mixture exposure of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and cadmium (Cd) causes kidney damage; however, the mechanism was not fully understood. The aryl hydrocarbon receptor (AhR) is a ligand-receptor transcription factor that plays an important role in the adaptive response or metabolic detoxification of environmental toxins. Thus, this study aimed to examine the role of AhR in kidney toxicity. BDE-47 (50 µM) or Cd (5 µM) exposure reduced cell viability in renal tubular epithelial cells (HKC), with a larger effect observed in co-treatment. The cell morphology presented pyroptotic changes, including swollen cells, large bubbles, and plasma membrane pore formation. The gene expressions of AhR, heat shock protein 90 (Hsp90), AhR nuclear translocator (ARNT), and cytochrome P450 1B1 (CYP1B1) were increased, while CYP1A1 was decreased. Reactive oxygen species (ROS) were generated, which was reduced by the AhR antagonist CH223191. The apoptosis, necrosis, and intracellular lactated hydrogenase (LDH) release was elevated, and this was attenuated by N-acetylcysteine (NAC). Furthermore, the pyroptosis pathway was activated with increased protein levels of cleaved-caspase-3 and gasdermin E N-terminal (GSDME-NT), while caspase-8, caspase-3, and GSDME were decreased. These effects were alleviated by NAC and CH223191. Our data demonstrate a combined effect of BDE-47 and Cd on nephrotoxicity by activating AhR to induce ROS contributing to GSDME-dependent pyroptosis, and retardation of the AhR pathway could reduce this toxicity.


Assuntos
Cádmio , Receptores de Hidrocarboneto Arílico , Receptores de Hidrocarboneto Arílico/metabolismo , Cádmio/toxicidade , Caspase 3/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Piroptose , Éter , Células Epiteliais/metabolismo
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