Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 378
Filtrar
2.
Surgery ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38734502

RESUMO

BACKGROUND: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. METHODS: We analyzed patients who underwent curative-intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identified through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. RESULTS: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms' concordance indices in the training cohort were 0.777 (95% confidence interval 0.759-0.800) and 0.719 (95% confidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems (P < .001). Nomograms accurately stratified risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. CONCLUSION: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti-recurrence therapy.

3.
J Am Chem Soc ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781401

RESUMO

Unactivated aliphatic alkenes are particularly desirable as starting materials because they are readily accessible in large quantities, but the enantioselective intermolecular reductive coupling of unactivated alkenes with imines is challenging. In this paper, we report a method for nickel-catalyzed intermolecular reductive coupling reactions between aliphatic alkenes and imines to yield chiral amines with excellent enantioselectivities and good linear selectivities. The reaction conditions are compatible with a broad range of aliphatic alkenes, including those derived from bioactive molecules. The success of this method can be attributed to the use of newly developed monodentate chiral spiro phosphine ligands.

4.
Cancer Sci ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695305

RESUMO

Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced-stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post-surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced-stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field.

5.
Am J Surg ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38777717

RESUMO

BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients. METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs. RESULTS: Of 497 elderly patients, 157 (31.6 â€‹%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 â€‹%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 â€‹% vs. 72.1 â€‹%, P â€‹< â€‹0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 â€‹% confidence interval 1.879-6.198, P â€‹< â€‹0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy. CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.

6.
Mol Cancer ; 23(1): 71, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575922

RESUMO

It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.


Assuntos
Carcinogênese , Neoplasias , Humanos , Transformação Celular Neoplásica/genética , Morte Celular , Nutrientes , Oxigênio , Apoptose
7.
Cell Biol Int ; 48(6): 821-834, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38436129

RESUMO

Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low-dose 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear. In this study, we treated immortalized human keratinocytes (HaCaT cells) with low-dose ALA-PDT (0.5 mmol/L, 3 J/cm2). Through RNA-sequencing analysis, we identified that low-dose ALA-PDT modulated autophagy-related pathways in keratinocytes and pinpointed Unc-51-like kinase 1 (ULK1) as a key gene involved. Western blot results revealed that low-dose ALA-PDT treatment upregulated the expression of autophagy-related proteins Beclin-1 and LC3-II/LC3-I ratio. Notably, low-dose ALA-PDT regulated autophagy by inducing an appropriate level of reactive oxygen species (ROS), transiently reducing mitochondrial membrane potential, and decreasing adenosine triphosphate production; all these processes functioned on the AMP-activated protein kinase (AMPK)/ULK1 pathway to activate autophagy. Finally, we simulated external environmental damage using ultraviolet B (UVB) at a dose of 60 mJ/cm2 and observed that low-dose ALA-PDT mitigated UVB-induced cell apoptosis; however, this protective effect was reversed when using the autophagy inhibitor 3-methyladenine. Overall, these findings highlight how low-dose ALA-PDT enhances antistress ability in HaCaT cells through controlling ROS generation and activating the AMPK/ULK1 pathway to arouse cellular autophagy.


Assuntos
Proteínas Quinases Ativadas por AMP , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Autofagia , Queratinócitos , Transdução de Sinais , Humanos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Autofagia/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Aminolevulínico/farmacologia , Células HaCaT , Potencial da Membrana Mitocondrial/efeitos dos fármacos
8.
Cancer Gene Ther ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38351139

RESUMO

RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through multiple pathways. The function and expression of these epigenetic regulators have gradually become a hot topic in cancer research. Mutation and regulation of noncoding RNA, especially lncRNA, play a major role in cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions and its dysregulation can promote tumor occurrence and metastasis. In this review, we summarize N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine modifications in lncRNAs. Furthermore, we discuss the relationship between epigenetic RNA modification and lncRNA interaction and cancer progression in various cancers. Therefore, this review gives a comprehensive understanding of the mechanisms by which RNA modification affects the progression of various cancers by regulating lncRNAs, which may shed new light on cancer research and provide new insights into cancer therapy.

9.
Hepatobiliary Surg Nutr ; 13(1): 16-28, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38322222

RESUMO

Background: Hepatectomy is the preferred treatment for solitary hepatocellular carcinoma (HCC) without macrovascular invasion and distant metastasis, but long-term survival remains unsatisfactory in certain patients. We sought to identify whether the grading severity of microscopic vascular invasion (MVI) was associated with recurrence and survival among patients with solitary HCC. Methods: Consecutive patients who underwent hepatectomy for solitary HCC were identified from a multicenter prospectively-collected database. Patients were categorized into three groups according to the MVI grading system proposed by the Liver Cancer Pathology Group of China: M0 (no MVI), M1 (1-5 sites of MVI occurring ≤1.0 cm away from the tumor), and M2 (>5 sites occurring ≤1.0 cm or any site occurring >1 cm away from the tumor). Recurrence-free survival (RFS) and overall survival (OS) were compared among the groups. Results: Among 227 patients, 97 (42.7%), 83 (36.6%), and 47 (20.7%) patients had M0, M1, and M2, respectively. Median RFS rates among patients with M0, M1, and M2 were 38.3, 35.1, 11.6 months, respectively, while OS rates were 66.8, 62.3, 30.6 months, respectively (both P<0.001). Multivariate Cox-regression analyses demonstrated that both M1 and M2 were independent risk factors for RFS (hazard ratio 1.20, 95% CI: 1.03-1.89, P=0.040; and hazard ratio 1.67, 95% CI: 1.06-2.64, P=0.027) and OS (hazard ratio 1.28, 95% CI: 1.05-2.07, P=0.035; and hazard ratio 1.97, 95% CI: 1.15-3.38, P=0.013). Conclusions: Grading severity of MVI was independently associated with RFS and OS after hepatectomy for solitary HCC. Enhanced surveillance for recurrence and potentially adjuvant therapy may be considered for patients with MVI, especially individuals with more severe MVI grading (M2).

10.
Emerg Microbes Infect ; 13(1): 2313848, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38318858

RESUMO

Few studies focused on human papillomavirus (HPV) in male patients. This study aimed to explore the detection rate and genotyping of HPV among male patients in Beijing to provide a reference for formulating prevention strategies for HPV infection. The cross-sectional study was conducted in Beijing Chaoyang Hospital from November 2015 to March 2023. It covered male patients from the urology and dermatology departments. Fifteen high-risk HPV genotypes were detected by the multiplex real-time polymerase chain reaction method. The overall detection rate of HPV was 25.19% (1288/5114, 95% confidence interval [CI] 24.00%-26.38%), of which the single infection rate was 16.99% (869/5114, 95% CI 15.97%-18.05%) and the co-infection rate was 8.19% (419/5114, 95% CI 7.46%-8.98%). The detection rate of HPV was 40.77% (521/1278), 35.58% (58/163), 32.69% (101/309), 31.91% (60/188), 12.63% (299/2367), and 32.35% (131/405) among male patients with balanitis, warts, rash, urethritis, prostatitis, and other urinary inflammation, respectively (P < 0.001). The top five HPV genotypes were HPV-52, HPV-58, HPV-16, HPV-51, and HPV-66. After the first positive HPV test, the proportion of male patients who turned negative was 22.47% within 3 months, 26.40% within 3-6 months, 24.72% within 6-12 months, 17.98% within 12-24 months, and 8.43% more than 24 months. The detection rate of HPV was high among male patients from the urology and dermatology departments in Beijing, which should be considered to develop HPV vaccines with better prevention effects.


Assuntos
Infecções por Papillomavirus , Humanos , Masculino , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Genótipo , Estudos Transversais , Pequim/epidemiologia , Papillomavirus Humano , Papillomaviridae/genética , China/epidemiologia , Prevalência
11.
Am J Surg ; 232: 87-94, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38238192

RESUMO

BACKGROUND: The Albumin-Bilirubin (ALBI) score, widely used in predicting long-term prognosis for patients with hepatocellular carcinoma (HCC), has limitations due to serum albumin variability. This study aimed to develop and validate the Prealbumin-Bilirubin (preALBI) score as a reliable alternative. METHODS: A multicenter cohort of HCC patients who underwent hepatectomy was randomly divided into the training and validation cohorts. The preALBI score was developed using Cox regression models within the training cohort, incorporating serum prealbumin and bilirubin levels as crucial determinants. The survival predictive accuracy was evaluated and compared between the preALBI score with two other staging systems, including the ALBI score and the Child-Pugh grade. RESULTS: A total of 2409 patients were enrolled. In the training cohort, the preALBI score demonstrated superior performance in predicting long-term survival after hepatectomy. The preALBI score was associated with the best monotonicity of gradients (linear trend χ2: 72.84) and homogeneity (likelihood ratio χ2: 74.69), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.663, 0.654, and 0.644, respectively). In addition, the preALBI was the most informative staging system in predicting survival (Akaike information criterion: 11325.65).The results remained consistent in both training and validation cohorts, indicating its reliable performance across different populations. CONCLUSION: The preALBI score, leveraging the stability of prealbumin, represents a promising tool for better patient stratification, providing more accurate prognostic predictions than the ALBI score and the Child-Pugh grade.


Assuntos
Bilirrubina , Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Pré-Albumina , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/sangue , Masculino , Feminino , Pré-Albumina/metabolismo , Pré-Albumina/análise , Bilirrubina/sangue , Pessoa de Meia-Idade , Prognóstico , Idoso , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Adulto
12.
J Nanobiotechnology ; 22(1): 24, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191388

RESUMO

The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs' preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs' biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials.


Assuntos
Antibacterianos , Nanopartículas Magnéticas de Óxido de Ferro , Animais , Humanos
13.
Chin J Integr Med ; 30(2): 135-142, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37434030

RESUMO

OBJECTIVE: To investigate the effect of Huangqin Decoction (HQD) on nuclear factor erythroid 2 related-factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway by inducing the colitis-associated carcinogenesis (CAC) model mice with azoxymethane (AOM)/dextran sodium sulfate (DSS). METHODS: The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS/MS) to determine the molecular constituents of HQD. Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table, including control, model (AOM/DSS), mesalazine (MS), low-, medium-, and high-dose HQD (HQD-L, HQD-M, and HQD-H) groups, 8 mice in each group. Except for the control group, the mice in the other groups were intraperitoneally injected with AOM (10 mg/kg) and administrated with 2.5% DSS orally for 1 week every two weeks (totally 3 rounds of DSS) to construct a colitis-associated carcinogenesis mouse model. The mice in the HQD-L, HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925, 5.85, and 11.7 g/kg, respectively; the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg (totally 11 weeks). The serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Nrf2, HO-1, and inhibitory KELCH like ECH-related protein 1 (Keap1) in colon tissue were detected by quantitative real-time PCR, immunohistochemistry, and Western blot, respectively. RESULTS: LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin, paeoniflorin, and glycyrrhizic acid. Compared to the control group, significantly higher MDA levels and lower SOD levels were observed in the model group (P<0.05), whereas the expressions of Nrf2 and HO-1 were significantly decreased, and the expression of Keap1 increased (P<0.01). Compared with the model group, serum MDA level was decreased and SOD level was increased in the HQD-M, HQD-H and MS groups (P<0.05). Higher expressions of Nrf2 and HO-1 were observed in the HQD groups. CONCLUSION: HQD may regulate the expression of Nrf2 and HO-1 in colon tissue, reduce the expression of MDA and increase the expression of SOD in serum, thus delaying the progress of CAC in AOM/DSS mice.


Assuntos
Antioxidantes , Colite , Camundongos , Animais , Antioxidantes/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Scutellaria baicalensis/química , Scutellaria baicalensis/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espectrometria de Massas em Tandem , Camundongos Endogâmicos C57BL , Colite/complicações , Colite/tratamento farmacológico , Colite/metabolismo , Transdução de Sinais , Carcinogênese , Azoximetano/farmacologia , Superóxido Dismutase/metabolismo
14.
Sci Total Environ ; 917: 169306, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38103614

RESUMO

Microcystins (MCs) are the most common cyanobacterial toxins. Epidemiological investigation showed that exposure to MCs can cause gastro-intestinal symptoms, gastroenteritis and gastric cancer. MCs can also accumulate in and cause histopathological damage to stomach. However, the exact mechanisms by which MCs cause gastric injury were unclear. In this study, Wistar rats were administrated 50, 75 or 100 µg microcystin-LR (MC-LR)/kg, body mass (bm) via tail vein, and histopathology, response of anti-oxidant system and the proteome of gastric tissues at 24 h after exposure were studied. Bleeding of fore-stomach and gastric corpus, inflammation and necrosis in gastric corpus and exfoliation of mucosal epithelial cells in gastric antrum were observed following acute MC-LR exposure. Compared with controls, activities of superoxide dismutase (SOD) were significantly greater in gastric tissues of exposed rats, while activities of catalase (CAT) were less in rats administrated 50 µg MC-LR/kg, bm, and concentrations of glutathione (GSH) and malondialdehyde (MDA) were greater in rats administrated 75 or 100 µg MC-LR/kg, bm. These results indicated that MC-LR could disrupt the anti-oxidant system and cause oxidative stress. The proteomic results revealed that MC-LR could affect expressions of proteins related to cytoskeleton, immune system, gastric functions, and some signaling pathways, including platelet activation, complement and coagulation cascades, and ferroptosis. Quantitative real-time PCR (qRT-PCR) analysis showed that transcriptions of genes for ferroptosis and gastric function were altered, which confirmed results of proteomics. Overall, this study illustrated that MC-LR could induce gastric dysfunction, and ferroptosis might be involved in MC-LR-induced gastric injury. This study provided novel insights into mechanisms of digestive diseases induced by MCs.


Assuntos
Antioxidantes , Toxinas Marinhas , Microcistinas , Ratos , Animais , Antioxidantes/metabolismo , Microcistinas/toxicidade , Microcistinas/metabolismo , Proteômica , Fígado/metabolismo , Ratos Wistar , Estresse Oxidativo , Glutationa/metabolismo , Estômago
15.
Adv Sci (Weinh) ; 11(9): e2305508, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38145957

RESUMO

Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post-surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti-recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti-recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Perda Sanguínea Cirúrgica , Hidrogéis/uso terapêutico , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/patologia , Nanopartículas/uso terapêutico , Microambiente Tumoral
16.
Mol Immunol ; 165: 19-27, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38134517

RESUMO

OBJECTIVE: The primary pathological changes of rheumatoid arthritis (RA) include chronic synovial inflammation, bone destruction, and aggressive pannus formation on cartilage, in which angiogenesis plays a critical role. B7-H3, an important immune checkpoint molecule, represents a novel target in tumor therapy and plays a significant role in the pathogenesis of autoimmune diseases. However, its biological mechanism in RA remains unclear. METHODS: Hematoxylin-eosin (HE) staining and immunohistochemistry were used to explore the histological characteristics and expression of B7-H3, CD34, and vascular endothelial growth factor (VEGF) in patients with RA and collagen-induced arthritis (CIA) mice. ELISA was used to detect VEGF, soluble B7-H3, and disease markers in the peripheral blood of patients. A monoclonal anti-B7-H3 antibody was used to treat CIA mice by blocking B7-H3-mediated signaling. RESULTS: The ELISA and HE staining results showed a positive correlation between the expression of B7-H3 and the degree of joint cavity destruction and pannus formation. B7-H3 expression also correlated with increased expression of the vessel biomarkers CD34 and VEGF. Anti-B7-H3 effectively reduced pannus formation in CIA mice. CONCLUSION: B7-H3 modulates angiogenic activity in the joint synovium, demonstrating its therapeutic value in the context of RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Humanos , Camundongos , Angiogênese , Anticorpos Monoclonais/uso terapêutico , Artrite Experimental/metabolismo , Artrite Reumatoide/patologia , Inflamação/patologia , Neovascularização Patológica/metabolismo , Membrana Sinovial/patologia , Fatores de Transcrição , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Nutrients ; 15(19)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37836546

RESUMO

OBJECTIVES: To develop and validate a prognostic nomogram based on baseline nutritional and inflammatory parameters for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving chemotherapy combination programmed death-1 (PD-1) inhibitor. METHODS: This retrospective study analyzed 131 patients with dmNPC (88 and 43 in the training and validation cohorts, respectively) between March 2017 and November 2020. All these patients received chemotherapy combined with PD-1 inhibitor treatment. We identified independent risk factors using univariate and multivariate Cox regression analyses and established a nomogram to predict the progression-free survival (PFS). The predictive accuracy of the nomogram was evaluated and independently validated. RESULTS: Baseline nutritional risk index (NRI), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), uric acid (UA), and post-treatment Epstein-Barr virus (EBV) DNA were used to develop a nomogram that could divide patients into favorable- and unfavorable-prognosis groups. The median PFS (mPFS) was significantly longer in the favorable-prognosis group compared to the unfavorable-prognosis group (35.10 months [95% CI: 27.36-42.84] vs. 7.23 months [95% CI: 6.50-7.97]; p = 0.001). All results were confirmed in the validation cohort. CONCLUSIONS: The proposed model improved the prognostic risk stratification for patients with dmNPC undergoing chemotherapy combined with PD-1 inhibitor treatment.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Herpesvirus Humano 4/genética , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Prognóstico , DNA Viral
18.
Environ Pollut ; 339: 122730, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37838314

RESUMO

Smoking is a serious global health issue. Cigarette smoking contains over 7000 different chemicals. The main harmful components include nicotine, acrolein, aromatic hydrocarbons and heavy metals, which play the key role for cigarette-induced inflammation and carcinogenesis. Growing evidences show that cigarette smoking and its components exert a remarkable impact on regulation of immunity and dysregulated immunity promotes inflammation and cancer. Therefore, this comprehensive and up-to-date review covers four interrelated topics, including cigarette smoking, inflammation, cancer and immune system. The known harmful chemicals from cigarette smoking were summarized. Importantly, we discussed in depth the impact of cigarette smoking on the formation of inflammatory or tumor microenvironment, primarily by affecting immune effector cells, such as macrophages, neutrophils, and T lymphocytes. Furthermore, the main molecular mechanisms by which cigarette smoking induces inflammation and cancer, including changes in epigenetics, DNA damage and others were further summarized. This article will contribute to a better understanding of the impact of cigarette smoking on inducing inflammation and cancer.


Assuntos
Fumar Cigarros , Neoplasias , Humanos , Fumar Cigarros/efeitos adversos , Neoplasias/induzido quimicamente , Inflamação , Nicotiana/química , Nicotina , Microambiente Tumoral
19.
Environ Sci Technol ; 57(42): 16065-16074, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37843047

RESUMO

Understanding the mechanisms underlying perfluoroalkyl acids (PFAAs) translocation, distribution, and accumulation in wheat-soil ecosystems is essential for agricultural soil pollution control and crop ecological risk assessment. This study systematically investigated the translocation of 13 PFAAs under different iron and nitrogen fertilization conditions in a wheat-soil ecosystem. Short-chain PFAAs including PFBA, PFPeA, PFHxA, and PFBS mostly accumulated in soil solution (10.43-55.33%) and soluble extracellular polymeric substances (S-EPS) (11.39-14.77%) by the adsorption to amino- (-NH2) and hydroxyl (-OH) groups in dissolved organic matter (DOM). Other PFAAs with longer carbon chain lengths were mostly distributed on the soil particle surface by hydrophobic actions (74.63-94.24%). Iron-nitrogen amendments triggered (p < 0.05) soil iron-nitrogen cycling, rhizospheric reactive oxygen species fluctuations, and the concentration increases of -NH2 and -OH in the DOM structure. Thus, the accumulation capacity of PFAAs in soil solution and root EPS was increased. In sum, PFAAs' translocation from soil particles to wheat root was synergistically reduced by iron and nitrogen fertilization through increased adsorption of soil particles (p < 0.05) and the retention of soil solution and root EPSs. This study highlights the potential of iron-nitrogen amendments in decreasing the crop ecological risks to PFAAs' pollution.


Assuntos
Fluorocarbonos , Solo , Matéria Orgânica Dissolvida , Triticum , Ecossistema , Matriz Extracelular de Substâncias Poliméricas/química , Nitrogênio , Fluorocarbonos/análise
20.
Clin Respir J ; 17(12): 1246-1253, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37823412

RESUMO

BACKGROUND: When influenza A-related pneumonia is complicated by bacteria, aspergillus, and other infections, the disease is aggravated, while there is no research on the role of Epstein-Barr virus (EBV) on patients with influenza A-related pneumonia. This study aimed to evaluate the relationship between the isolation of EBV and influenza A-related pneumonia. METHODS: This is a clinical study based on the baseline data of a retrospective cohort. A total of 113 cases of influenza A-related pneumonia who underwent polymerase chain reaction test for isolation of EBV-DNA in lower respiratory tract specimens during six influenza seasons from 2013-2014 to 2018-2019 were enrolled. According to the results of EBV-DNA, patients were divided into EBV-positive group and EBV-negative group, and the role of EBV-DNA on patients with influenza A-related pneumonia was analyzed. Regression analysis was used to explore the potential risk factors for the development of moderate-to-severe acute respiratory distress syndrome (ARDS) in patients with influenza A-related pneumonia during hospitalization. RESULTS: Among 113 patients with influenza A-related pneumonia, there were 53 patients with EBV-positive and 60 patients with EBV-negative. The EBV-positive group had higher intensive care unit admission rate, hospital stay, invasive mechanical ventilation rate, extracorporeal membrane oxygenation rate, Sequential Organ Failure Assessment (SOFA) score, and moderate-to-severe ARDS rate. Patients were divided into severe group and mild group. Patients in severe group had lower lymphocyte count, platelet count, and albumin level, while the levels of aspartate aminotransferase, alanine transaminase, creatine kinase, lactic dehydrogenase, and total bilirubin were higher in severe group. The levels of D-dimer, serum ferritin, C-reactive protein, and procalcitonin were higher in severe group than those in the mild group. Multivariate logistic regression analysis revealed that the isolation of EBV (odds ratio = 2.713, 95% confidence interval: 1.094-6.729, P = 0.031) and lymphocyte count (odds ratio = 3.585, 95% confidence interval: 1.157-11.101, P = 0.027) were independent risk factors for moderate-to-severe ARDS in patients with influenza A-related pneumonia. CONCLUSION: The isolation rate of EBV in the lower respiratory tract was 46.9%. The length of hospital stays, intensive care unit admission rate, invasive mechanical ventilation rate, extracorporeal membrane oxygenation rate, SOFA score, and the proportion of moderate-to-severe ARDS in the EBV-positive group were higher than those in the EBV-negative group, while there was no effect on the death during hospitalization. The isolation of EBV in the lower respiratory tract and low lymphocyte count are independent risk factors for the development of moderate-to-severe ARDS in patients with influenza A-related pneumonia.


Assuntos
Infecções por Vírus Epstein-Barr , Influenza Humana , Pneumonia , Síndrome do Desconforto Respiratório , Humanos , Herpesvirus Humano 4/genética , Influenza Humana/complicações , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Projetos Piloto , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/epidemiologia , Estudos Retrospectivos , Estado Terminal , Pneumonia/complicações , Síndrome do Desconforto Respiratório/etiologia , DNA , Sistema Respiratório
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA