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1.
Mol Biol Evol ; 41(9)2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39271164

RESUMEN

Extremely aggressive behavior, as the special pattern, is rare in most species and characteristic as contestants severely injured or killed ending the combat. Current studies of extreme aggression are mainly from the perspectives of behavioral ecology and evolution, while lacked the aspects of molecular evolutionary biology. Here, a high-quality chromosome-level genome of the parasitoid Anastatus disparis was provided, in which the males exhibit extreme mate-competition aggression. The integrated multiomics analysis highlighted that neurotransmitter dopamine overexpression, energy metabolism (especially from lipid), and antibacterial activity are likely major aspects of evolutionary formation and adaptation for extreme aggression in A. disparis. Conclusively, our study provided new perspectives for molecular evolutionary studies of extreme aggression as well as a valuable genomic resource in Hymenoptera.


Asunto(s)
Agresión , Animales , Masculino , Genoma de los Insectos , Evolución Molecular , Avispas/genética , Adaptación Fisiológica/genética , Evolución Biológica , Adaptación Biológica/genética , Cromosomas de Insectos/genética
2.
Mucosal Immunol ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39127259

RESUMEN

Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections. Understanding why some individuals get more serious disease may help with diagnosis and treatment. One possible risk factor underlying severe disease is bacterial exposure before RSV infection. Bacterial exposure has been associated with increased respiratory viral-induced disease severity but the mechanism remains unknown. Respiratory bacterial infections or exposure to their pathogen associated molecular patterns (PAMPs) trigger innate immune inflammation, characterised by neutrophil and inflammatory monocyte recruitment and the production of inflammatory cytokines. We hypothesise that these changes to the lung environment alter the immune response and disease severity during subsequent RSV infection. To test this, we intranasally exposed mice to LPS, LTA or Acinetobacter baumannii (an airway bacterial pathogen) before RSV infection and observed an early induction of disease, measured by weight loss, at days 1-3 after infection. Neutrophils or inflammatory monocytes were not responsible for driving this exacerbated weight loss. Instead, exacerbated disease was associated with increased IL-1α and TNF-α, which orchestrated the recruitment of innate immune cells into the lung. This study shows that exposure to bacterial PAMPs prior to RSV infection increases the expression of IL-1α and TNF-α, which dysregulate the immune response resulting in exacerbated disease.

3.
Bioorg Med Chem Lett ; 111: 129903, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39053704

RESUMEN

Nitrobenzoxadiazole (NBD)-incorporated naphthalene diimide derivatives were designed and synthesized as candidates of antitumor agents with cytotoxicity against human pancreatic cancer cell MIA PaCa-2. Among these, compounds 1NND and 3NND exhibited fluorescent "turn-off" property toward human telomeric G-quadruplex (G4), which allows the direct measurement of dissociation constant (Kd) of ligands against G4 by fluorescence titration method. Notably, the compound 1NND not only exhibited great cytotoxic activity against MIA PaCa-2 with a half maximal inhibitory concentration (IC50) of 77.9 nM, but also exhibited high affinity against G4 with Kd of 1.72 µM. Furthermore, the target binding properties were investigated by circular dichroism (CD) spectra and further studied by molecular docking methods.


Asunto(s)
Antineoplásicos , Diseño de Fármacos , G-Cuádruplex , Imidas , Naftalenos , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/farmacología , G-Cuádruplex/efectos de los fármacos , Imidas/química , Imidas/farmacología , Imidas/síntesis química , Ligandos , Simulación del Acoplamiento Molecular , Estructura Molecular , Naftalenos/química , Naftalenos/farmacología , Naftalenos/síntesis química , Relación Estructura-Actividad
4.
NPJ Vaccines ; 9(1): 118, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926455

RESUMEN

Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and "prime-pull" regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen.

6.
Quant Imaging Med Surg ; 14(5): 3572-3580, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38720868

RESUMEN

Background: Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary balloon dilatation (PTBD) is a challenge in resolving biliary-enteric anastomotic occlusive strictures (BEAOS) and/or coexisting stones. The biliary-enteric anastomosis (BEA) often cannot be seen because of the surgically altered gastrointestinal anatomy. Here, a technique that combined percutaneous compliant-occluded distal cholangiography and the maintenance of a large-bore catheter is described to resolve this issue. Methods: A retrospective review of 10 patients who presented with BEAOS with/without coexisting stones who were treated with percutaneous compliant balloon-occluded distal cholangiography, bile duct stone removal, and the maintenance of a large-bore catheter between February 2017 and January 2021 was performed. Treatment response, laboratory examinations, including hepatic function tests, routine blood tests, and blood electrolytes, complications, and imaging data were evaluated. Paired t-tests were used to investigate the difference of laboratory examinations before and after the procedure. Results: All 10 cases were technically successful. A total of 9 stones in 6 patients were successfully removed by the compliant balloon. All catheters were removed after the patency of the stricture was confirmed by percutaneous transhepatic cholangiography (PTHC) 6 months later. No severe adverse events occurred during the perioperative period. There were 2 patients who experienced episodes of cholangitis during the follow-up period (mean, 17 months; range, 4-24 months), and neither BEAOS nor bile duct stones recurred within 2 years after the procedure. White blood cells (WBC), total bilirubin (TB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were (6.0±1.4)×109/L and (6.0±1.6)×109/L (P=0.91), 31.4±15.7 and 29.6±10.3 µmol/L (P=0.74), 50.8±20.0 and 85.8±67.0 U/L (P=0.16), and 42.6±15.2 and 71.8±44.9 U/L (P=0.09) pre and postintervention, respectively. Conclusions: Percutaneous transhepatic compliant balloon-occluded distal cholangiography and the maintenance of a large-bore catheter probably provide an effective and safe alternative method for resolving BEAOS and/or coexisting stones.

7.
Mucosal Immunol ; 17(2): 272-287, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38382577

RESUMEN

Respiratory viral infections remain a major cause of hospitalization and death worldwide. Patients with respiratory infections often lose weight. While acute weight loss is speculated to be a tolerance mechanism to limit pathogen growth, severe weight loss following infection can cause quality of life deterioration. Despite the clinical relevance of respiratory infection-induced weight loss, its mechanism is not yet completely understood. We utilized a model of CD 8+ T cell-driven weight loss during respiratory syncytial virus (RSV) infection to dissect the immune regulation of post-infection weight loss. Supporting previous data, bulk RNA sequencing indicated significant enrichment of the interleukin (IL)-1 signaling pathway after RSV infection. Despite increased viral load, infection-associated weight loss was significantly reduced after IL-1α (but not IL-1ß) blockade. IL-1α depletion resulted in a reversal of the gut microbiota changes observed following RSV infection. Direct nasal instillation of IL-1α also caused weight loss. Of note, we detected IL-1α in the brain after either infection or nasal delivery. This was associated with changes in genes controlling appetite after RSV infection and corresponding changes in signaling molecules such as leptin and growth/differentiation factor 15. Together, these findings indicate a lung-brain-gut signaling axis for IL-1α in regulating weight loss after RSV infection.


Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Humanos , Animales , Ratones , Linfocitos T , Interleucina-1alfa , Calidad de Vida , Pulmón , Interleucina-1 , Pérdida de Peso , Ratones Endogámicos BALB C
8.
CVIR Endovasc ; 7(1): 16, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38294662

RESUMEN

PURPOSE: To analyze the selection of endovascular treatment strategies and the efficacy of various locations and types of splenic artery aneurysms (SAAs). METHODS: Sixty-three cases of patients diagnosed with SAA from January 2016 to October 2021 were collected, and their clinical data and follow-up results were analyzed. RESULTS: Among the 63 patients, 55 had true SAAs, and 8 had false SAAs. The average diameter of the true SAAs was 2.0 ± 0.8 cm. There were 10 cases of intra-aneurysm embolization, 24 cases of intra-aneurysm and aneurysm-bearing artery embolization, 10 cases of bare stent-assisted coil embolization, and 11 cases of stent grafts. The false SAAs had an average diameter of 2.3 ± 1.1 cm. Aneurysm-bearing artery embolization was applied in 5 cases, and stent grafts were applied in 3 cases. The incidence of complications after embolization of the aneurysm-bearing artery was higher (P < 0.01). Postembolization syndrome occurred in 10 patients; 7 patients developed splenic infarction to varying degrees, 1 patient had mildly elevated blood amylase, and 1 patient developed splenic necrosis with abscess formation, all of which improved after active treatment. The average length of hospital stay was 5.5 ± 3.2 days. The average follow-up time was 17.2 ± 16.1 months, and the aneurysm cavity of all patients was completely thrombotic. CONCLUSION: Endovascular treatments of SAAs are safe and effective. For various locations and types of SAAs, adequate selection of treatment is necessary. Stent grafts are recommended for their safety, economy, practicality, and preservation of the physiological functions of the human body.

9.
Int J Biometeorol ; 68(2): 333-349, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38052751

RESUMEN

Over the past three decades, there has been a significant global climate change characterized by an increase in the intensity and frequency of extreme climate events. The vegetation status in Qinghai Province has undergone substantial changes, which are more pronounced than other regions in the Qinghai-Tibet Plateau. However, a clear understanding of the response characteristics of plateau vegetation to extreme climate events is currently lacking. In this study, we investigated the response of net primary productivity (NPP) to different forms of extreme climate events across regions characterized by varying levels of aridity and elevation gradients. Specifically, we observed a significant increase in NPP in relatively arid regions. Our findings indicate that, in relatively arid regions, single episodes of high-intensity precipitation have a pronounced positive effect (higher correlation) on NPP. Furthermore, in high-elevation regions (4000-6000 m), both the intensity and frequency of precipitation events are crucial factors for the increase in regional NPP. However, continuous precipitation can have significant negative impacts on certain areas within relatively wet regions. Regarding temperature, a reduction in the number of frost days within a year has been shown to lead to a significant increase in NPP in arid regions. This reduction allows vegetation growth rate to increase in regions where it was limited by low temperatures. Vegetation conditions in drought-poor regions are expected to continue to improve as extreme precipitation intensifies and extreme low-temperature events decrease.


Asunto(s)
Ecosistema , Modelos Teóricos , China , Tibet , Temperatura , Cambio Climático
10.
EMBO Mol Med ; 15(12): e17932, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-37970627

RESUMEN

Viruses are vulnerable as they transmit between hosts, and we aimed to exploit this critical window. We found that the ubiquitous, safe, inexpensive and biodegradable small molecule propylene glycol (PG) has robust virucidal activity. Propylene glycol rapidly inactivates a broad range of viruses including influenza A, SARS-CoV-2 and rotavirus and reduces disease burden in mice when administered intranasally at concentrations commonly found in nasal sprays. Most critically, vaporised PG efficiently abolishes influenza A virus and SARS-CoV-2 infectivity within airborne droplets, potently preventing infection at levels well below those tolerated by mammals. We present PG vapour as a first-in-class non-toxic airborne virucide that can prevent transmission of existing and emergent viral pathogens, with clear and immediate implications for public health.


Asunto(s)
COVID-19 , Virus de la Influenza A , Gripe Humana , Animales , Ratones , Humanos , Aerosoles y Gotitas Respiratorias , COVID-19/prevención & control , Glicoles de Propileno , Mamíferos
11.
J Thorac Imaging ; 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37982518

RESUMEN

PURPOSE: The purpose of this study was to assess the efficiency and safety of computed tomography (CT)-guided percutaneous biopsy of lung lesions with electromagnetic (EM) navigation and compare them with those of conventional approaches. MATERIALS AND METHODS: Seventy-nine patients with lung or liver lesions who needed biopsies were enrolled in this trial. All patients were randomly assigned to the E group underwent CT-guided percutaneous biopsies with the EM navigation system or to the C group treated with conventional approaches. RESULTS: In total, 27 patients with lung lesions were assigned to the E group, and 20 patients were assigned to the C group. The diagnostic success rate was 92.6% and 95% in both groups, respectively (P>0.9999). The median number of needle repositions in the E group was less than that in the C group (2.0 vs. 2.5, P=0.03). The positioning success rate with 1 or 2 needle repositions for the E group was significantly higher than the C group (81.5% vs. 50%, P=0.03). The median accuracy of the puncture location in the E group was better than that in the C group (2.0 vs. 6.6 mm, P<0.0001). The total procedure time lengthened in the E group compared with the C group (30.5±1.6 vs. 18.3±1.7 min, P<0.0001), but the number of CT acquisitions was not significantly different (P=0.08). There was no significant difference in complication incidence between the 2 groups (P=0.44). CONCLUSION: The EM navigation system is an effective and safe auxiliary tool for CT-guided percutaneous lung biopsy, but lengthen the procedure time. TRIAL REGISTRATION: ChiCTR2100043361, registered February 9, 2021-retrospectively registered (http://www.medresman.org.cn/uc/project/projectedit.aspx?proj=7591).

12.
Mol Ther Nucleic Acids ; 34: 102045, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37876532

RESUMEN

The response to mRNA vaccines needs to be sufficient for immune cell activation and recruitment, but moderate enough to ensure efficacious antigen expression. The choice of the cap structure and use of N1-methylpseudouridine (m1Ψ) instead of uridine, which have been shown to reduce RNA sensing by the cellular innate immune system, has led to improved efficacy of mRNA vaccine platforms. Understanding how RNA modifications influence the cell intrinsic immune response may help in the development of more effective mRNA vaccines. In the current study, we compared mRNA vaccines in mice against influenza virus using three different mRNA formats: uridine-containing mRNA (D1-uRNA), m1Ψ-modified mRNA (D1-modRNA), and D1-modRNA with a cap1 structure (cC1-modRNA). D1-uRNA vaccine induced a significantly different gene expression profile to the modified mRNA vaccines, with an up-regulation of Stat1 and RnaseL, and increased systemic inflammation. This result correlated with significantly reduced antigen-specific antibody responses and reduced protection against influenza virus infection compared with D1-modRNA and cC1-modRNA. Incorporation of m1Ψ alone without cap1 improved antibodies, but both modifications were required for the optimum response. Therefore, the incorporation of m1Ψ and cap1 alters protective immunity from mRNA vaccines by altering the innate immune response to the vaccine material.

13.
J Cancer Res Ther ; 19(4): 904-909, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37675715

RESUMEN

Aims: To compare the diagnostic efficacy and safety of CT-guided percutaneous core needle biopsy (CNB) and fine-needle aspiration (FNA) for pancreatic lesions. Methods and Material: A total of 176 patients with 176 pancreatic lesions who visited our hospital between January 2016 and March 2021 were retrospectively analyzed. They were divided into three groups: FNA group A (<1.5 cm between the lesion and great vessels necessitating FNA), FNA group B, and CNB (the latter two with ≥1.5 cm between the lesion and great vessels necessitating FNA). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and postoperative. The statistical analysis was done using Statistical Package for the Social Sciences version 17.0. Results: One hundred and seventy six patient's specimens all met the requirements. There were no statistically significant differences in sensitivity, specificity, positive predictive value, negative predictive value, and accuracy between the CNB group and FNA group B, (P > 0.05). Thirteen samples submitted for genetic testing (5 in CNB group, 4 in each of the FNA groups A and B) all met the standards of next-generation sequencing gene detection. The main complications of these groups included abdominal pain, fever, and hyperamylasemia. Conclusions: CT-guided percutaneous FNA and CNB have similar diagnostic efficacy for pancreatic biopsy. Furthermore, FNA has a wide range of puncture indications and is very safe. Like CNB, the obtained tissue through FNA can be genetically tested to guide clinical treatment.


Asunto(s)
Linfoma de Burkitt , Neoplasias Pancreáticas , Humanos , Biopsia con Aguja Fina , Biopsia con Aguja Gruesa , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico , Páncreas/diagnóstico por imagen
14.
DNA Res ; 30(2)2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36999569

RESUMEN

Tetraena mongolica is an endangered xerophytic shrub with high ecological value for the restoration of desert vegetation because of its high tolerance to drought and heat stress. Here, we generated a high-quality chromosome-level reference genome of T. mongolica by combining PacBio HiFi data and Hi-C sequencing technologies, which was approximately 1.12 Gb (contig N50 of 25.5 Mb) in size and contained 61,888 protein-coding genes; repetitive sequences comprised 44.8% of the genome. This genome of T. mongolica is the first published genome sequence of a member of the order Zygophyllales. Genome analysis showed that T. mongolica has undergone a recent whole genome duplication event, and a recent burst of long terminal repeat insertions afterward, which may be responsible for its genome size expansion and drought adaptation. We also conducted searches for gene homologues and identified terpene synthase (TPS) gene families and candidate genes involved in triacylglycerol biosynthesis. The T. mongolica genome sequence could aid future studies aimed at functional gene identification, germplasm resource management, molecular breeding efforts, as well as evolutionary studies of Fabids and angiosperm taxa.


Asunto(s)
Cromosomas , Genoma , Anotación de Secuencia Molecular , Secuencias Repetitivas de Ácidos Nucleicos , Genoma de Planta
15.
Mol Ther Nucleic Acids ; 31: 29-42, 2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36589712

RESUMEN

To be effective, RNA vaccines require both in situ translation and the induction of an immune response to recruit cells to the site of immunization. These factors can pull in opposite directions with the inflammation reducing expression of the vaccine antigen. We investigated how formulation affects the acute systemic cytokine response to a self-amplifying RNA (saRNA) vaccine. We compared a cationic polymer (pABOL), a lipid emulsion (nanostructured lipid carrier, NLC), and three lipid nanoparticles (LNP). After immunization, we measured serum cytokines and compared the response to induced antibodies against influenza virus. Formulations that induced a greater cytokine response induced a greater antibody response, with a significant correlation between IP-10, MCP-1, KC, and antigen-specific antibody titers. We then investigated how innate immune sensing and signaling impacted the adaptive immune response to vaccination with LNP-formulated saRNA. Mice that lacked MAVS and are unable to signal through RIG-I-like receptors had an altered cytokine response to saRNA vaccination and had significantly greater antibody responses than wild-type mice. This indicates that the inflammation induced by formulated saRNA vaccines is not solely deleterious in the induction of antibody responses and that targeting specific aspects of RNA vaccine sensing might improve the quality of the response.

16.
Eur Radiol ; 33(3): 1779-1791, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36149482

RESUMEN

OBJECTIVES: To explore the risk factors for recurrence of arterial complications after pancreatectomy during the period of covered stent implantation and to provide some opinions on peri-stent implantation management. METHODS: Data on patients implanted with covered stents due to arterial complications after pancreatectomy between January 2017 and December 2021 were analyzed retrospectively. Technical success, clinical success, recurrence, and survival were evaluated to elucidate the practicability of covered stents. Wilson score, Random Forest, logistic regression, and Pearson's chi-square test with bootstrap aggregation were performed for determining the perioperative risk factors for recurrence. RESULTS: Among all fifty-five patients, success stent implantation (technical success) was achieved 100%. Patients who were hemodynamically stabilized without further treatment for artery complications in situ (clinical success) accounted for 89.1%. Based on statistical analysis, pre-stent implantation pancreatic fistula was identified as a robust recurrence-related risk factor for preoperative assessment (p = 0.02, OR = 4.5, 95% CI [1.2, 16.9]; pbootstrap = 0.02). Post-stent implantation pancreatic fistula (p = 0.01, OR 4.5, 95% CI [1.4, 14.6]; pbootstrap < 0.05) and SMA branches or GDA stumps (p = 0.02, OR 3.4, 95% CI [1.1, 10.3]) were relevant to recurrence. The survival rate during hospitalization was 87.3%. All survivors were free from recurrence during the subsequent follow-up. Vasospasm and stent occlusion were observed as short-term and long-term complications, respectively. CONCLUSION: A covered stent implantation is a feasible and effective treatment option for post-pancreatectomy arterial complications. Rigorous management of pancreatic fistula, timely detection of problems, sensible strategies during stent implantation, and reasonable anticoagulation therapy are necessary for a better prognosis. KEY POINTS: • A covered stent is feasible for various artery-related complications after pancreatectomy and has an ideal therapeutic effect. • Pancreatic fistula during the perioperative period of the covered stent is an independent risk factor for recurrent arterial complications and SMA branches or GDA stumps are prone to be recurrent offending arteries. • Rigorous management of pancreatic fistula, timely detection of problems, sensible strategies during stent implantation, and reasonable anticoagulation therapy are necessary for a better prognosis.


Asunto(s)
Fístula Pancreática , Stents , Humanos , Estudios Retrospectivos , Arterias , Resultado del Tratamiento , Medición de Riesgo , Anticoagulantes
17.
Front Immunol ; 13: 961350, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36172359

RESUMEN

Background: The main objective of this study was to analyze the effects of KRAS/TP53 mutation status and tumor sideness on the immune microenvironment of colorectal cancer using integrated scRNA-seq data. Methods: A total of 78 scRNA-seq datasets, comprising 42 treatment-naive colorectal tumors, 13 tumor adjacent tissues and 23 normal mucosa tissues were included. Standardized Seurat procedures were applied to identify cellular components with canonical cell marks. The batch-effect was assessed and corrected using harmony algorithm. The scMetabolism algorithm was used for single-cell metabolic analysis. The results and clinical significance were further validated using immunofluorescent-staining and TCGA-COAD datasets. Immune-infiltration scores of bulk-RNA-seq data were estimated using ssGSEA. The presto-wilcoxauc algorithm was used to identify differentially enriched genes or pathways across different subgroups. Two-sided p-value less than 0.05 was considered statistically significant. Results: We refined the landscape of functional immune cell subtypes, especially T cells and myeloid cells, across normal mucosa, tumor adjacent and tumor tissue. The existence and function of two states of exhausted CD8+ T (Tex) subtypes in colorectal cancer, and FOLR2+ LYVE1+ macrophages indicating unfavorable prognosis in colorectal cancer were identified and validated. The diverse tumor mutation status reshaped the immune cell function and immune checkpoint ligands/receptors (ICLs/ICRs) expression pattern. Importantly, the KRAS/TP53 dual mutations significantly reduced the major energy metabolic functions in immune cells, and promoted the cell-to-cell communications towards immunosuppression in colorectal cancers. The results revealed LAG3, CD24-SIGLEC10 and HBEGF-CD9 pathways as potential therapeutic targets for dual mutant colorectal cancers. Conclusions: We revealed that the immune microenvironment underwent a gradual remodeling with an enrichment of immunosuppressive myeloid cells from normal mucosa to tumor regions in colorectal cancers. Moreover, we revealed the metabolic heterogeneity of tumor-infiltrating immune cells and suggested that the KRAS/TP53 dual mutation may impair antitumor immunity by reducing T and myeloid cell energy metabolism and reshaping cellular interactions toward immunosuppression.


Asunto(s)
Neoplasias Colorrectales , Receptor 2 de Folato , Neoplasias Colorrectales/patología , Humanos , Ligandos , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Análisis de Secuencia de ARN , Microambiente Tumoral/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
18.
Front Oncol ; 12: 973357, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36059634

RESUMEN

Background: Hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT) may be able to have TACE through stent implantation into the portal vein with thrombosis to recover portal blood flow. Purpose: The goal of this study was to compare clinical results of conventional transcatheter arterial chemoembolization (C-TACE) and doxorubicin-eluting bead transcatheter arterial chemoembolization (D-TACE) combined with endovascular brachytherapy in HCC patients with MPVTT. Methods: This study was a retrospective controlled study with follow-up dates spanning from Mar 2015 to Feb 2020. Patients with both HCC and MPVTT were divided into two groups. Portal vein stents with iodine-125 seed strands were implanted first; then, C-TACE or D-TACE was administered to all patients. Objective response rates were assessed. Results: A total of 26 patients were enrolled, with 13 in each group. During follow-up, the portal stent patency times were 112.3 ± 98.2 days in the C-TACE group and 101.7 ± 90.4 days in the D-TACE group. The time to disease progression was 42 days in the C-TACE group and 120 days in the D-TACE group (p=0.03). The overall survival time from the first intervention procedure was 216 days in the C-TACE group and 239 days in the D-TACE group (p=0.047). The D-TACE group was superior to the C-TACE group in terms of progression-free survival (PFS) and overall survival (OS) times. Conclusion: Endovascular implantation of brachytherapy combined with TACE is safe and effective in HCC patients with MPVTT. This combination therapy may be helpful for survival benefits to patients with stage BCLC-C HCC.

19.
Macromol Biosci ; 22(10): e2200189, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35895675

RESUMEN

Self-folding is a rapidly evolving method for converting flat objects into three-dimensional (3D) structures. However, because there are few materials with suitable properties, the application of self-folding in tissue engineering has been hindered greatly. Herein, a novel self-folding hydrogel using  conformational transition mechanism is developed by employing  photocrosslinkable silk fibroin and gelatin composite hydrogel. It is hypothesized that differences in the amount of beta-sheet (ß-sheet) formation between the upper and lower layers will supply additional folding stress and drive the self-folding behavior of a bilayer patch, which can improve the mechanical properties and long-term stability of the self-folded structure. In this study, the impact of various proportions of ß-sheets in composite hydrogels on their swelling, mechanics, and internal microstructures are investigated. Subsequently, the folding process parameters are optimized, and diffusion through the folded tubular structure is studied with a perfusion test. Finally, it is proven that the self-folding hydrogel system is cytocompatible and can be utilized to build a 3D coculture system of "endothelial cells-smooth muscle cells". These findings suggest that the self-folding hydrogel can be a promising candidate for applications in blood vessel tissue engineering and regenerative medicine.


Asunto(s)
Fibroínas , Células Endoteliales , Fibroínas/química , Gelatina/química , Hidrogeles/química , Hidrogeles/farmacología , Ingeniería de Tejidos/métodos
20.
Curr Oncol ; 29(6): 3950-3961, 2022 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-35735425

RESUMEN

BACKGROUND: Tumors at the hepatocaval confluence are difficult to treat, either surgically or ablatively. METHODS: A retrospective longitudinal study on patients ineligible for thermal ablation who underwent computed tomography-guided IRE for hepatic tumors at the hepatocaval confluence was conducted. Factors analyzed included patient and tumor characteristics, IRE procedure details, treatment-related complications, and prognosis. RESULTS: Between 2017 and 2021, 21 patients at our institute received percutaneous IRE. Of the 38 lesions, 21 were at the hepatocaval confluence. Complete ablation was achieved in all cases. Local and distant recurrence was observed in 4.8% (1/21) and 42.6% (9/21) of the ablated tumors, respectively. All postcava remained perfused at follow-up, except for 1 (4.8%) hepatic vein near the lesion found to be temporarily occluded and restored within 1 month. The ratio of the maximum diameter of ablation area at 1, 3, and 6 months post procedure compared to that immediately after IRE was 0.68 (0.50-0.84), 0.49 (0.27-0.61), and 0.38 (0.25-0.59), respectively. Progression-free survival of the patients with recurrence was 121 (range, 25-566) days. Four (19.0%) patients died at the end of follow-up with median overall survival of 451.5 (range, 25-716) days. CONCLUSIONS: IRE could be a safe and effective treatment for hepatic tumors at the hepatocaval confluence. This article provides valuable prognostic data; further clinical research is needed for better prognosis.


Asunto(s)
Ablación por Catéter , Neoplasias Hepáticas , Electroporación/métodos , Humanos , Neoplasias Hepáticas/cirugía , Estudios Longitudinales , Estudios Retrospectivos
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