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2.
Acta Pharm Sin B ; 14(5): 2077-2096, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799619

RESUMO

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors, and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor progression. Herein, we demonstrated that salvianic acid A (SAA) played a pivotal role in contributing to vascular normalization in the tumor-bearing mice, thereby improving delivery and effectiveness of the chemotherapeutic agent. SAA was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells (HUVECs) exposed to hypoxia. Mechanistically, SAA was inclined to directly bind to the glycolytic enzyme PKM2, leading to a dramatic decrease in endothelial glycolysis. More importantly, SAA improved the endothelial integrity via activating the ß-Catenin/Claudin-5 signaling axis in a PKM2-dependent manner. Our findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

3.
Quant Imaging Med Surg ; 14(4): 2938-2945, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617160

RESUMO

Background: Biliary stent dysfunction is challenging to treat in clinic. The retrograde track method (RTM) has a promising clinical application in the reopening of dysfunctional biliary stents. This study aimed to evaluate the clinical value of the RTM in reopening dysfunctional biliary stents. Methods: From February 2013 to January 2020, 151 patients underwent percutaneous transhepatic biliary interventional procedures for reopening dysfunctional biliary stents at the First Affiliated Hospital of Zhengzhou University, and 25 patients (12 females, 13 males; mean age 63.12 years old) underwent the RTM after anterograde reopening dysfunction biliary stent failure. Technical success, clinical success, irradiation dose, procedure time, complications, and overall survival (OS) were recorded, and levels of total bilirubin (TBIL), direct bilirubin (DB), alanine aminotransferase (ALT), albumin (ALB), and carbohydrate antigen-199 (CA-199) were compared before treatment and 1 month after treatment. Results: The technical and clinical success rates were 100% and 96%, respectively, and the irradiation dose and procedure times were 774.07±330.80 mGy and 45.16±9.48 min, respectively. Two patients (8%) experienced major complications. The median OS was 10.73 months [95% confidence interval (CI): 9.37-12.09]. Compared with pretreatment values, the mean levels at 1 month after RTM administration for TBIL (189.47±59.20 vs. 44.65±16.12 µmol/L), DB (144.21±55.83 vs. 27.95±13.86 µmol/L), ALT (89.62±30.85 vs. 49.44±14.25 U/L), and CA-199 (584.59±269.82 vs. 176.76±100.68 U/mL) showed significant decreases, while that of ALB (36.32±2.05 vs. 40.22±1.95 g/L) showed a significant increase (all P values <0.05). Conclusions: RTM is an effective alternative treatment method when anterograde reopening of a dysfunctional biliary stent occurs.

4.
Abdom Radiol (NY) ; 49(5): 1646-1652, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38592493

RESUMO

PURPOSE: To evaluate the efficacy and safety of a novel technique for removal of migrated esophageal stent (MES) under fluoroscopy. METHODS: From January 2009 to April 2023, 793 patients with a dysphagia score of 3-4 underwent esophageal stenting at our center, and 25 patients (mean age: 70.06 years old; male/female: 15/10) underwent stent removal using "loop method" under fluoroscopy. The primary outcomes were technical success and complications. The secondary outcomes were procedure time, radiation exposure, biochemical indicators [white blood cell (WBC), hemoglobin (Hb), platelet (PLT), albumin (ALB), alanine transaminase (ALT), total bilirubin (TB), urea nitrogen (UN) and C-reactive protein] of pre- and post-treatment at 2 weeks. RESULTS: Technical success was 100% without major complications. The mean procedure time was (39.44 ± 9.28) minutes, which showed no statistical significance between benign (n = 5) and malignant (n = 20) group [(42.40 ± 8.85) vs (38.71 ± 9.46) mins, p > 0.05]. The mean radiation exposure was (332.88 ± 261.47) mGy, which showed no statistical significance between benign and malignant group [(360.74 ± 231.43) vs (325.92 ± 273.54) mGy, p > 0.05]. Pre- and post-procedure Hb [(114.46 ± 11.96) vs. (117.57 ± 13.12) g/L] and ALB [(42.26 ± 3.39) vs. (44.12 ± 3.77) g/L] showed significant difference (p < 0.05), while WBC, PLT, CRP, and ALT showed no significance (p > 0.05). CONCLUSION: Fluoroscopy-guided "Loop method" for MES removal is an effective and safe alternative technique.


Assuntos
Remoção de Dispositivo , Stents , Humanos , Feminino , Fluoroscopia , Masculino , Idoso , Remoção de Dispositivo/métodos , Migração de Corpo Estranho/diagnóstico por imagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Transtornos de Deglutição/etiologia , Radiografia Intervencionista/métodos , Idoso de 80 Anos ou mais
5.
Insights Imaging ; 15(1): 108, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609579

RESUMO

OBJECTIVE: To study the predictive factors of false negatives in the diagnosis of biliary stricture (BS) by percutaneous transluminal clamp biopsy (PTCB). METHOD: From January 2016 to January 2021, 194 patients with a high suspicion of malignant tumors due to BS underwent PTCB during biliary drainage at our department. The final diagnosis was confirmed by postoperative pathology, other tissue or cell evidence, or medical imaging follow-up. Univariate and multivariate regression analyses were performed on the pathological results, summarizing the independent risk factors for false-negative value (FNV) to help further clinical diagnosis and treatment. RESULTS: Of the 194 cases, 176 and 18 cases were finally diagnosed as malignant and benign BS, respectively, compared to 144 and 50 cases by PTCB, including 32 false-negative cases. The sensitivity, specificity, false-positive value, and FNV of PTCB were 81.8%, 100%, 0%, and 18.2%, respectively. Multivariate analysis showed that non-cholangiocarcinoma BS was an independent risk factor for FNV of PTCB (odds ratio 7.5 (95% CI 1.74-32.6), p < 0.01). CONCLUSION: PTCB is an effective minimally invasive interventional technique for BS diagnosis. Non-cholangiocarcinoma BS is an independent risk factor for FNV. CRITICAL RELEVANCE STATEMENT: Identifying factors that are predictive of false-negative results by percutaneous transluminal clamp biopsy in the setting of biliary stricture may have a guiding effect on clinical practice. KEY POINTS: • Factors predictive of false negatives in the diagnosis of biliary stricture etiology by PTCB may aid in the interpretation of results. • Non-cholangiocarcinoma BS is an independent risk factor for FNV on PTCB. • PTCB is an effective minimally invasive interventional technique for BS diagnosis.

6.
Int J Biol Macromol ; 265(Pt 2): 130994, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38518950

RESUMO

Biofouling remains a persistent challenge within the domains of biomedicine, tissue engineering, marine industry, and membrane separation processes. Multifunctional hydrogels have garnered substantial attention due to their complex three-dimensional architecture, hydrophilicity, biocompatibility, and flexibility. These hydrogels have shown notable advances across various engineering disciplines. The antifouling efficacy of hydrogels typically covers a range of strategies to mitigate or inhibit the adhesion of particulate matter, biological entities, or extraneous pollutants onto their external or internal surfaces. This review provides a comprehensive review of the antifouling properties and applications of hydrogels. We first focus on elucidating the fundamental principles for the inherent resistance of hydrogels to fouling. This is followed by a comprehensive investigation of the methods employed to enhance the antifouling properties enabled by the hydrogels' composition, network structure, conductivity, photothermal properties, release of reactive oxygen species (ROS), and incorporation of silicon and fluorine compounds. Additionally, we explore the emerging prospects of antifouling hydrogels to alleviate the severe challenges posed by surface contamination, membrane separation and wound dressings. The inclusion of detailed mechanistic insights and the judicious selection of antifouling hydrogels are geared toward identifying extant gaps that must be bridged to meet practical requisites while concurrently addressing long-term antifouling applications.


Assuntos
Incrustação Biológica , Hidrogéis , Hidrogéis/farmacologia , Hidrogéis/química , Incrustação Biológica/prevenção & controle , Interações Hidrofóbicas e Hidrofílicas , Silício
7.
Curr Issues Mol Biol ; 46(3): 1799-1809, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38534734

RESUMO

The tumor metastasis suppressor gene CD82/KAI1 has been demonstrated to impact human trophoblast invasion and migration. Communication between trophoblasts and decidual stromal cells plays a crucial role in controlling the normal invasiveness of trophoblasts. However, whether CD82/KAI1 is involved in decidualization and what role it plays remain unclear. CD82/KAI1 demonstrates specific spatiotemporal expression patterns in stromal cells undergoing decidualization during pregnancy. This is observed in both naturally pregnant females post-implantation and pseudopregnant mice undergoing induced decidualization, as detected through in situ hybridization and immunofluorescence. CD82/KAI1 expression showed a significant time-dependent increase in cultured stromal cells after 24 and 48 h of progesterone (P4) and estrogen (E2) treatment. This was accompanied by a notable upregulation of decidualization markers, including cyclin D3 and PR. After transducing stromal cells with the adenovirus-overexpressing CD82/KAI1 for 48 h, the expression of cyclin D3 protein increased. Meanwhile, there was an attenuated expression of CD82/KAI1 due to an adenovirus siRNA knockdown, whereas cyclin D3 and PR expressions were not affected. Our findings suggest a potential role of CD82/KAI1 in regulating the process of decidualization, providing insights into stromal cell differentiation.

8.
Int J Mol Sci ; 25(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38473926

RESUMO

Since its inception, induced pluripotent stem cell (iPSC) technology has been hailed as a powerful tool for comprehending disease etiology and advancing drug screening across various domains. While earlier iPSC-based disease modeling and drug assessment primarily operated at the cellular level, recent years have witnessed a significant shift towards organoid-based investigations. Organoids derived from iPSCs offer distinct advantages, particularly in enabling the observation of disease progression and drug metabolism in an in vivo-like environment, surpassing the capabilities of iPSC-derived cells. Furthermore, iPSC-based cell therapy has emerged as a focal point of clinical interest. In this review, we provide an extensive overview of non-integrative reprogramming methods that have evolved since the inception of iPSC technology. We also deliver a comprehensive examination of iPSC-derived organoids, spanning the realms of the nervous system, cardiovascular system, and oncology, as well as systematically elucidate recent advancements in iPSC-related cell therapies.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes Induzidas/metabolismo , Organoides/metabolismo , Terapia Baseada em Transplante de Células e Tecidos , Diferenciação Celular
9.
BMC Cancer ; 24(1): 265, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38403626

RESUMO

OBJECTIVES: To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). METHODS: Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan-Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. RESULTS: The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8 months. The median PFS was 10.0 months (95% CI: 8.9-11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15 ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8 months (95% CI: 27.1-34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15 ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12 months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. CONCLUSIONS: RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.


Assuntos
Braquiterapia , Neoplasias Colorretais , Humanos , Prognóstico , Estadiamento de Neoplasias , Antígeno Carcinoembrionário , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/patologia , Pulmão/patologia
10.
Int J Biol Sci ; 20(3): 1110-1124, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322116

RESUMO

At present, tumor metastasis still remains the leading contributor to high recurrence and mortality in cancer patients. There have been no clinically effective therapeutic strategies for treating patients with metastatic cancer. In recent years, a growing body of evidence has shown that the pre-metastatic niche (PMN) plays a crucial role in driving tumor metastasis. Nevertheless, a clear and detailed understanding of the formation of PMN is still lacking given the fact that PMN formation involves in a wealth of complicated communications and underlying mechanisms between primary tumors and metastatic target organs. Despite that the roles of numerous components including tumor exosomes and extracellular vesicles in influencing the evolution of PMN have been well documented, the involvement of cancer-associated fibroblasts (CAFs) in the tumor microenvironment for controlling PMN formation is frequently overlooked. It has been increasingly recognized that fibroblasts trigger the formation of PMN by virtue of modulating exosomes, metabolism and so on. In this review, we mainly summarize the underlying mechanisms of fibroblasts from diverse origins in exerting impacts on PMN evolution, and further highlight the prospective strategies for targeting fibroblasts to prevent PMN formation.


Assuntos
Fibroblastos Associados a Câncer , Exossomos , Vesículas Extracelulares , Neoplasias , Humanos , Estudos Prospectivos , Neoplasias/metabolismo , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Fibroblastos/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Microambiente Tumoral , Metástase Neoplásica/patologia
11.
Quant Imaging Med Surg ; 14(1): 852-860, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38223073

RESUMO

Background: The sampling of vascular obstruction diseases remains a challenge in clinical practice. This retrospective study aimed to evaluate the feasibility, accuracy, and safety of intravascular forceps biopsy (IVFB) for the diagnosis of vascular obstructive diseases. Methods: From January 2015 to January 2022, of the total of 35 patients who underwent IVFB (21 male, 14 female; mean age 60±11 years; range, 39-81 years), 32 (91.4%) did so during interventional planned revascularization procedures and 3 (8.6%) did so due so due to inaccessible or failed percutaneous access. The outcomes of technical success, biopsy times, patient radiation dose (PRD), complications, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy rate (AR) were analyzed. Results: The technical success of IVFB was 100%. The median number of biopsies taken per biopsy session and PRD were 4.0 (range, 3-6) and 712.6 mGy (range, 383.4-1,450.8), respectively. The sensitivity, specificity, PPV, NPV, and AR of IVFB were 87.5% (21/24), 100% (11/11), 100% (21/21), 78.6% (11/14), and 91.4% (32/35), respectively. There were no complications related to IVFB. Conclusions: IVFB is a technically feasible and safe technique with good diagnostic value. The procedure should be considered in patients who are not suitable for percutaneous access, show indistinct imaging characteristics, or are scheduled to undergo revascularization procedure.

12.
iScience ; 26(9): 107704, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37680480

RESUMO

Platelets have been widely recognized as a bona fide mediator of malignant diseases, and they play significant roles in influencing various aspects of tumor progression. Paracrine interactions between platelets and tumor cells have been implicated in promoting the dissemination of malignant cells to distant sites. However, the underlying mechanisms of the platelet-tumor cell interactions for promoting hematogenous metastasis are not yet fully understood. We found that activated platelets with high expression of CD36 were prone to release a plethora of growth factors and cytokines, including high levels of PDGF-B, compared to resting platelets. PDGF-B activated the PDGFR-ß/COX-2 signaling cascade, which elevated an array of pro-inflammatory factors levels, thereby aggravating tumor metastasis. The collective administration of CD36 inhibitor and COX-2 inhibitor resolved the interactions between platelets and tumor cells. Collectively, our findings demonstrated that targeting the crosstalk between platelets and tumor cells offers potential therapeutic strategies for inhibiting tumor metastasis.

13.
Front Cell Dev Biol ; 11: 1217189, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601108

RESUMO

Post-translational modification (PTM) has a significant impact on cellular signaling and function regulation. In pancreatic ß cells, PTMs are involved in insulin secretion, cell development, and viability. The dysregulation of PTM in ß cells is clinically associated with the development of diabetes mellitus. Here, we summarized current findings on major PTMs occurring in ß cells and their roles in insulin secretion. Our work provides comprehensive insight into understanding the mechanisms of insulin secretion and potential therapeutic targets for diabetes from the perspective of protein PTMs.

14.
Front Neurosci ; 17: 1232308, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37583416

RESUMO

Ultrasound neuromodulation technology is a promising neuromodulation approach, with the advantages of noninvasiveness, high-resolution, deep penetration and good targeting, which aid in circumventing the side effects of drugs and invasive therapeutic interventions. Ultrasound can cause mechanical effects, activate mechanosensitive ion channels and alter neuronal excitability, producing biological effects. The structural determination of mechanosensitive ion channels will greatly contribute to our understanding of the molecular mechanisms underlying mechanosensory transduction. However, the underlying biological mechanism of ultrasonic neuromodulation remains poorly understood. Hence, this review aims to provide an outline of the properties of ultrasound, the structures of specific mechanosensitive ion channels, and their role in ultrasound neuromodulation.

15.
Water Res ; 244: 120447, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37574625

RESUMO

Natural solar-powered steam generation provides a promising strategy to deal with deteriorating water resources. However, the practical applications of this strategy are limited by the tedious manufacturing of structures at micro-nano levels to concentrate heat and transport water to heat-localized regions. Herein, this work reports the fabrication of hierarchically porous aerohydrogel with enhanced light absorption and thermal localization at the air-solid interface. This aerohydrogel steam generator is fabricated by a simple yet controllable micropore generation approach to assemble air and hydrogel into hierarchically porous gas-solid hybrids. The tunable micropore size in a wide range from 99±49µm to 316±58µm not only enables contrasting sunlight absorptance (0.2 - 2.5µm) by reducing the reflection of solar light but also harnesses water transportation to the heating region via a capillary force-driven liquid flow. Therefore, a solar-vapor conversion efficiency of 91.3% under one sun irradiation was achieved using this aerohydrogel evaporator, reaching a ready evaporation rate of 2.76kg m-2 h-1 and 3.71kg m-2 h-1 under one and two sun irradiations, respectively. Our work provides a versatile and scalable approach to engineering porous hydrogels for highly efficient steam generation and opens an avenue for other potential practical applications based on this aerohydrogel.


Assuntos
Vapor , Água , Porosidade , Transporte Biológico , Comércio
16.
Phytother Res ; 37(11): 4999-5016, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37491826

RESUMO

Numerous pharmacological effects of quercetin have been illustrated, including antiinflammation, antioxidation, and anticancer properties. In recent years, the antioxidant activity of quercetin has been extensively reported, in particular, its impacts on glutathione, enzyme activity, signaling transduction pathways, and reactive oxygen species (ROS). Quercetin has also been demonstrated to exert a striking antiinflammatory effect mainly by inhibiting the production of cytokines, reducing the expression of cyclooxygenase and lipoxygenase, and preserving the integrity of mast cells. By regulating oxidative stress and inflammation, which are regarded as two critical processes involved in the defense and regular physiological operation of biological systems, quercetin has been validated to be effective in treating a variety of disorders. Symptoms of these reactions have been linked to degenerative processes and metabolic disorders, including metabolic syndrome, cardiovascular, neurodegeneration, cancer, and nonalcoholic fatty liver disease. Despite that evidence demonstrates that antioxidants are employed to prevent excessive oxidative and inflammatory processes, there are still concerns regarding the expense, accessibility, and side effects of agents. Notably, natural products, especially those derived from plants, are widely accessible, affordable, and generally safe. In this review, the antioxidant and antiinflammatory abilities of the active ingredient quercetin and its application in oxidative stress-related disorders have been outlined in detail.


Assuntos
Estresse Oxidativo , Quercetina , Humanos , Quercetina/farmacologia , Quercetina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia
17.
J Ethnopharmacol ; 316: 116735, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37286115

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Based on the notion of traditional Chinese medicine, the theory of invigorating the circulation of blood is a prominent treatment for cancer in clinic. Therefore, Salvia miltiorrhiza Bunge, as a representative of Chinese medicine of invigorating the circulation of blood, has been proved to be an effective medicinal herb for treating cancer. AIM OF THE STUDY: To clarify the anti-cancer effect of Salvia miltiorrhiza Bunge aqueous extract (SMAE) on colorectal cancer (CRC) and investigate whether the therapeutic effect of SMAE was mediated by attenuating the infiltration of tumor-associated macrophages (TAMs) into the tumor microenvironment (TME). MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used for determined the main compounds of SMAE. MC38 cells were subcutaneously injected into the mice to establish the mouse model of CRC. Tumor growth curve was detected by tumor volume measurement. The model group received distilled water irrigation once a day. SMAE-treated group received 5 g/kg or 10 g/kg SMAE once a day. Anti-PD-L1 treated group received 5 mg/kg anti-PD-L1 once every three days. Protein expression of Cox2 and PD-L1 was determined by Western blot assay. The secretion levels of PGE2, IL-1ß, IL-6, MCP-1, and GM-CSF were evaluated through ELISA. The mRNA expression of CSF1, CCL2, CXCL1, CXCL2, and CXCL3 was measured by using RT-qPCR. Staining of Ki67, TUNEL and Caspase3 was used to investigate cell proliferation and apoptosis. Immunohistochemical staining was used to determine CD8+ T cell distribution. H&E staining was used to confirm histopathological changes. The expressions of F4/80 and CD68 were measured by flow cytometry to identify macrophages in tumors and lymph nodes. The number of CD8+ T cells and the expression of PD-1, IFN-γ, and Granzyme B (GZMB) were determined by flow cytometry. RESULTS: SMAE significantly retarded the growth of MC38 mouse colorectal cancer. SMAE strikingly inhibited the expression of Cox2 and impaired the secretion of PGE2 in tumors, contributing to the attenuated intra-tumoral infiltration of TAMs via Cox2/PGE2 cascade. Meanwhile, SMAE augmented anti-tumor immunity by the elevated proportion of IFN-γ+ CD8+ T cells and GZMB+ CD8+ T cells, which decreased the tumor load. Furthermore, the combination of SMAE and anti-PD-L1 showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in MC38 xenograft model. CONCLUSIONS: SMAE attenuated the infiltration of TAMs into tumors and synergized with anti-PD-L1 to treat CRC via modulating Cox2/PGE2 cascade.


Assuntos
Neoplasias Colorretais , Salvia miltiorrhiza , Salvia , Camundongos , Humanos , Animais , Macrófagos Associados a Tumor , Dinoprostona , Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Neoplasias Colorretais/tratamento farmacológico , Imunoterapia , Água , Microambiente Tumoral , Linhagem Celular Tumoral
18.
Microbiome ; 11(1): 96, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37131223

RESUMO

BACKGROUND: The Western dietary pattern, characterized by high consumption of fats and sugars, has been strongly associated with an increased risk of developing Crohn's disease (CD). However, the potential impact of maternal obesity or prenatal exposure to a Western diet on offspring's susceptibility to CD remains unclear. Herein, we investigated the effects and underlying mechanisms of a maternal high-fat/high-sugar Western-style diet (WD) on offspring's susceptibility to 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced Crohn's-like colitis. METHODS: Maternal dams were fed either a WD or a normal control diet (ND) for eight weeks prior to mating and continued throughout gestation and lactation. Post-weaning, the offspring were subjected to WD and ND to create four groups: ND-born offspring fed a normal diet (N-N) or Western diet (N-W), and WD-born offspring fed a normal (W-N) or Western diet (W-W). At eight weeks of age, they were administered TNBS to induce a CD model. RESULTS: Our findings revealed that the W-N group exhibited more severe intestinal inflammation than the N-N group, as demonstrated by a lower survival rate, increased weight loss, and a shorter colon length. The W-N group displayed a significant increase in Bacteroidetes, which was accompanied by an accumulation of deoxycholic acid (DCA). Further experimentation confirmed an increased generation of DCA in mice colonized with gut microbes from the W-N group. Moreover, DCA administration aggravated TNBS-induced colitis by promoting Gasdermin D (GSDMD)-mediated pyroptosis and IL-1beta (IL-1ß) production in macrophages. Importantly, the deletion of GSDMD effectively restrains the effect of DCA on TNBS-induced colitis. CONCLUSIONS: Our study demonstrates that a maternal Western-style diet can alter gut microbiota composition and bile acid metabolism in mouse offspring, leading to an increased susceptibility to CD-like colitis. These findings highlight the importance of understanding the long-term consequences of maternal diet on offspring health and may have implications for the prevention and management of Crohn's disease. Video Abstract.


Assuntos
Colite , Doença de Crohn , Efeitos Tardios da Exposição Pré-Natal , Humanos , Gravidez , Feminino , Camundongos , Animais , Doença de Crohn/induzido quimicamente , Dieta Ocidental/efeitos adversos , Colite/induzido quimicamente , Dieta Hiperlipídica/efeitos adversos , Ácido Desoxicólico , Camundongos Endogâmicos C57BL
19.
Abdom Radiol (NY) ; 48(7): 2456-2465, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37160766

RESUMO

PURPOSE: To analyze the risk factors and develop a clinical prediction model for early biliary infection (EBI) after percutaneous transhepatic biliary stenting (PTBS) in patients with malignant biliary obstruction (MBO). METHODS: The clinical data of 236 patients with MBO treated with PTBS from June 2012 to June 2021 were retrospectively analyzed. Independent risk factors were analyzed by univariate and multivariate logistic regression, and a nomogram model was constructed based on the results. Discrimination, calibration, and clinical usefulness of this model were further assessed. RESULTS: The technical success rate of PTBS was 100%, and EBI after PTBS was 20.3%. Multivariate logistic regression analysis showed that hilar MBO (P = 0.020), diabetes (P = 0.001), previous surgical or endoscopic intervention (P = 0.007), procedure time > 60 min (P = 0.007), and intraprocedural biliary hemorrhage (P = 0.003) were independent risk factors for EBI after PTBS. A nomogram model was developed to predict the probability of EBI. ROC curves showed good discrimination of the model (area under curve = 0.831). The calibration plot indicated that the predicted probability of EBI by this model was in good agreement with the actual probability of EBI. The DCA curves showed that the net benefit of nomogram-assisted decisions was higher than or equal to the net benefit of treatment for all or none at a wide threshold probability (0-0.8). CONCLUSION: The nomogram model based on the above independent risk factors can predict the probability of EBI and model-assisted treatment decisions contribute to improved clinical outcome. Therefore, MBO patients with probability of EBI > 0.20 based on the model should be recommended for perioperative broad-spectrum antibiotics and close monitoring.


Assuntos
Colestase , Neoplasias , Humanos , Estudos Retrospectivos , Modelos Estatísticos , Prognóstico , Colestase/diagnóstico por imagem , Colestase/cirurgia
20.
BMC Cancer ; 23(1): 418, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37161422

RESUMO

BACKGROUND: To evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with 125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA). METHODS: The clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS). RESULTS: The technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%, P > 0.05). Both early and late complications showed no significant differences between the two groups (P > 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P < 0.05). The mPFS and mOS were 4.3 (95% CI 3.9-4.7) months and 2.8 (95% CI 2.5-3.1) months and 13.5 (95% CI 10.7-16.3) months and 8.8 (95% CI 7.8-9.8) months, respectively, with significant differences (P < 0.05). CONCLUSION: PBD combined with ISSB is a safe and effective treatment for HCCA that can inhibit local tumors and prolong PFS and OS.


Assuntos
Neoplasias dos Ductos Biliares , Braquiterapia , Tumor de Klatskin , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Tumor de Klatskin/radioterapia , Braquiterapia/efeitos adversos , Estudos Retrospectivos , Drenagem , Anticorpos , Sementes , Neoplasias dos Ductos Biliares/radioterapia
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