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1.
Balkan Med J ; 41(2): 130-138, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38425017

RESUMO

Background: The changes in risk scores of inflammatory markers among patients diagnosed with hepatocellular carcinoma (HCC) remain unknown. Aims: To investigate the relationship between the inflammation risk score and other contributing factors and the prognostic outcomes in patients with moderate and advanced hepatitis B virus (HBV)-related HCC. Study Design: A retrospective cohort study. Methods: A total of 174 patients with moderate and advanced HBV related HCC were recruited to investigate the impact of stratified inflammatory risk scores and other associated risk factors on disease prognosis. Based on the optimal cut-off values calculated by the Youden index, the patients were divided into high-risk and low-risk groups based on their inflammation risk scores. Results: The study found a significant difference in median survival time between the low-risk and high-risk groups based on the inflammation risk score. Furthermore, the inflammation risk score, alpha-fetoprotein levels, transarterial chemoembolization treatment, and Barcelona Clinic Liver Cancer stage were identified as independent prognostic factors. The four variables were used to construct a prognostic nomogram for HCC. Subsequent evaluations using time-dependent receiver operating characteristic analysis and calibration curve tests revealed the nomogram's commendable discriminatory ability. As a result, the nomogram proved to be an effective tool for predicting survival at 2- to 4-years. Conclusion: The inflammation risk score has been identified as a significant prognostic factor for HBV-related HCC. The development of nomogram models has provided a practical and effective tool for determining the prognosis of patients affected by HBV-related HCC.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Vírus da Hepatite B , Nomogramas , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Inflamação
2.
Appl Environ Microbiol ; 90(4): e0193923, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38445866

RESUMO

The thermal bleaching percentage of coral holobionts shows interspecific differences under heat-stress conditions, which are closely related to the coral-associated microbiome. However, the ecological effects of community dynamics and interactions between Symbiodiniaceae and fungi on coral thermal bleaching susceptibility remain unclear. In this study, we analyzed the diversity, community structure, functions, and potential interaction of Symbiodiniaceae and fungi among 18 coral species from a high thermal bleaching risk atoll using next-generation sequencing. The results showed that heat-tolerant C3u sub-clade and Durusdinium dominated the Symbiodiniaceae community of corals and that there were no core amplicon sequence variants in the coral-associated fungal community. Fungal richness and the abundance of confirmed functional animal-plant pathogens were significantly positively correlated with the coral thermal bleaching percentage. Fungal indicators, including Didymellaceae, Chaetomiaceae, Schizophyllum, and Colletotrichum, were identified in corals. Each coral species had a complex Symbiodiniaceae-fungi interaction network (SFIN), which was driven by the dominant Symbiodiniaceae sub-clades. The SFINs of coral holobionts with low thermal bleaching susceptibility exhibited low complexity and high betweenness centrality. These results indicate that the extra heat tolerance of coral in Huangyan Island may be linked to the high abundance of heat-tolerant Symbiodiniaceae. Fungal communities have high interspecific flexibility, and the increase of fungal diversity and pathogen abundance was correlated with higher thermal bleaching susceptibility of corals. Moreover, fungal indicators were associated with the degrees of coral thermal bleaching susceptibility, including both high and intermediate levels. The topological properties of SFINs suggest that heat-tolerant coral have limited fungal parasitism and strong microbial network resilience.IMPORTANCEGlobal warming and enhanced marine heatwaves have led to a rapid decline in coral reef ecosystems worldwide. Several studies have focused on the impact of coral-associated microbiomes on thermal bleaching susceptibility in corals; however, the ecological functions and interactions between Symbiodiniaceae and fungi remain unclear. We investigated the microbiome dynamics and potential interactions of Symbiodiniaceae and fungi among 18 coral species in Huangyan Island. Our study found that the Symbiodiniaceae community of corals was mainly composed of heat-tolerant C3u sub-clade and Durusdinium. The increase in fungal diversity and pathogen abundance has close associations with higher coral thermal bleaching susceptibility. We first constructed an interaction network between Symbiodiniaceae and fungi in corals, which indicated that restricting fungal parasitism and strong interaction network resilience would promote heat acclimatization of corals. Accordingly, this study provides insights into the role of microorganisms and their interaction as drivers of interspecific differences in coral thermal bleaching.


Assuntos
Antozoários , Dinoflagelados , Microbiota , Animais , Antozoários/microbiologia , Recifes de Corais , Simbiose , Fungos/genética
3.
BMC Gastroenterol ; 24(1): 104, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481160

RESUMO

BACKGROUND: The recurrence rate and mortality rate among postoperative pancreatic cancer patients remain elevated. This study aims to develop and validate the cancer-specific survival period for individuals who have undergone pancreatic cancer surgery. METHODS: We extracted eligible data from the Surveillance, Epidemiology, and End Results database and randomly divided all patients into a training cohort and an internal validation cohort. External validation was performed using a separate Chinese cohort. The nomogram was developed using significant risk factors identified through univariate and multivariate Cox proportional hazards regression. The effectiveness of the nomogram was assessed using the area under the time-dependent curve, calibration plots, and decision curve analysis. Kaplan-Meier survival curves were utilized to visualize the risk stratification of nomogram and AJCC stage. RESULTS: Seven variables were identified through univariate and multivariate analysis to construct the nomogram. The consistency index of the nomogram for predicting overall survival was 0.683 (95% CI: 0.675-0.690), 0.689 (95% CI: 0.677-0.701), and 0.823 (95% CI: 0.786-0.860). The AUC values for the 1- and 2-year time-ROC curves were 0.751 and 0.721 for the training cohort, 0.731 and 0.7554 for the internal validation cohort, and 0.901 and 0.830 for the external validation cohorts, respectively. Calibration plots demonstrated favorable consistency between the predictions of the nomogram and actual observations. Moreover, the decision curve analysis indicated the clinical utility of the nomogram, and the risk stratification of the nomogram effectively identified high-risk patients. CONCLUSION: The nomogram guides clinicians in assessing the survival period of postoperative pancreatic cancer patients, identifying high-risk groups, and devising tailored follow-up strategies.


Assuntos
Nomogramas , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Pâncreas , Povo Asiático , China/epidemiologia
4.
Adv Mater ; : e2308126, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38533956

RESUMO

The behavior of tissue resident cells can be influenced by the spatial arrangement of cellular interactions. Therefore, it is of significance to precisely control the spatial organization of various cells within multicellular constructs. It remains challenging to construct a versatile multicellular scaffold with ordered spatial organization of multiple cell types. Herein, a modular multicellular tissue engineering scaffold with ordered spatial distribution of different cell types is constructed by assembling varying cell-laden modules. Interestingly, the modular scaffolds can be disassembled into individual modules to evaluate the specific contribution of each cell type in the system. Through assembling cell-laden modules, the macrophage-mesenchymal stem cell (MSC), endothelial cell-MSC, and chondrocyte-MSC co-culture models are successfully established. The in vitro results indicate that the intercellular cross-talk can promote the proliferation and differentiation of each cell type in the system. Moreover, MSCs in the modular scaffolds may regulate the behavior of chondrocytes through the nuclear factor of activated T-Cells (NFAT) signaling pathway. Furthermore, the modular scaffolds loaded with co-cultured chondrocyte-MSC exhibit enhanced regeneration ability of osteochondral tissue, compared with other groups. Overall, this work offers a promising strategy to construct a multicellular tissue engineering scaffold for the systematic investigation of intercellular cross-talk and complex tissue engineering.

5.
Nat Mater ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413811

RESUMO

Solvation dynamics critically affect charge transport. Spectroscopic experiments and computer simulations show that these dynamics in aqueous systems occur on a picosecond timescale. In the case of organic electrolytes, however, conflicting values ranging from 1 to several 100 picoseconds have been reported. We resolve this conflict by studying mixtures of an organic polymer and a lithium salt. Lithium ions coordinate with multiple polymer chains, resulting in temporary crosslinks. Relaxation of these crosslinks, detected by quasielastic neutron scattering, are directly related to solvation dynamics. Simulations reveal a broad spectrum of relaxation times. The average timescale for solvation dynamics in both experiment and simulation is one nanosecond. We present the direct measurement of ultraslow dynamics of solvation shell break-up in an electrolyte.

6.
Clin Case Rep ; 12(2): e8453, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38292225

RESUMO

AlphaMissense is proficient in predicting the clinical classification of missense variants. we utilized AlphaMissense to find disease-relevant variants within a polymicrobial pulmonary infection case. Exome sequencing was performed in this patient, and AlphaMissense and Phenolyzer were combined to investigate disease-relevant variants screening from exome sequencing results.

7.
Microbiol Spectr ; 12(2): e0243623, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38174936

RESUMO

Fungiidae have shown increased thermal adaptability in coral reef ecosystems under global warming. This study analyzes the evolutionary divergence and microbial communities of Fungiidae in the Sanjiao Reef of the southern South China Sea and explores the impact of coral evolution radiation and microbial dynamics on the heat tolerance of Fungiidae. The results found that Cycloseris was an ancient branch of Fungiidae, dating back approximately 147.8953 Mya, and Fungiidae differentiated into two ancestral clades (clades I and II) before 107.0312 Ma. Fungiidae exhibited specific symbioses with the Cladocopium C27 sub-clade. Notably, the Cladocopium C1 sub-clade has a high relative abundance in clade I, whereas the heat-tolerant Cladocopium C40 and C3u sub-clades subdominante in clade II. Regarding bacterial communities, Cycloseris costulata, the earliest divergent species, had higher bacterial ß-diversity, while the latest divergent species, Lithophyllon scabra, displayed lower bacterial α-diversity and higher community stability. Beneficial bacteria dominante Fungiidae's bacterial community (54%). The co-occurrence network revealed that microbial networks in clade II exhibited lower complexity and greater resilience than those in clade I. Our study highlights that host evolutionary radiation and microbial communities shaped Fungiidae's thermal tolerance. The variability in subdominant Symbiodiniaceae populations may contribute to interspecific differences in thermal tolerance along the evolutionary branches of Fungiidae. The presence of abundant beneficial bacteria may further enhance the thermal ability of the Fungiidae. Furthermore, the later divergent species of Fungiidae have stronger heat tolerance, possibly driven by the increased regulation ability of the host on the bacterial community, greater microbial community stability, and interaction network resistance.IMPORTANCECoral reefs are facing significant threats due to global warming. The heat tolerance of coral holobionts depends on both the coral host and its microbiome. However, the association between coral evolutionary radiation and interspecific differences in microbial communities remains unclear. In this study, we investigated the role of evolutionary radiation and microbial community dynamics in shaping the thermal acclimation potential of Fungiidae in the Sanjiao Reef of the southern South China Sea. The study's results suggest that evolutionary radiation enhances the thermal tolerance of Fungiidae. Fungiidae species that have diverged more recently have exhibited a higher presence of heat-tolerant Symbiodiniaceae taxa, more stable bacterial communities, and a robust and resilient microbial interaction network, improving the thermal adaptability of Fungiidae. In summary, this study provides new insights into the thermal adaptation patterns of corals under global warming conditions.


Assuntos
Antozoários , Dinoflagelados , Microbiota , Animais , Antozoários/microbiologia , Antozoários/fisiologia , Recifes de Corais , Aclimatação , Bactérias , China , Dinoflagelados/fisiologia
8.
BMC Cancer ; 24(1): 137, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279090

RESUMO

BACKGROUND: Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported. METHODS: Immunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells. RESULTS: FOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p < 0.01). The positive rates of FOXP1 were significantly lower in patients with poor differentiation, lymph node metastasis, invasion into surrounding organs, and advanced stages (p < 0.05). Notably, patients with FOXP1 positivity had better outcomes (overall survival) than those with FOXP1 negativity (p < 0.05), as revealed by Kaplan-Meier survival analysis. Moreover, Cox multivariate analysis showed that negative FOXP1 expression, advanced TNM stages, invasion, and lymph node metastasis were independent prognostic risk factors in patients with ICC. Lastly, overexpression of FOXP1 inhibited the proliferation, migration, and invasion of ICC cells and promoted apoptosis, whereas knockdown of FOXP1 had the opposite role. CONCLUSION: Our findings suggest that FOXP1 may serve as a novel outcome predictor for ICC as well as a tumor suppressor that may contribute to cancer treatment.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Prognóstico , Metástase Linfática/patologia , Proliferação de Células , Linhagem Celular Tumoral , Fatores de Transcrição/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo
9.
Mar Environ Res ; 193: 106284, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38048660

RESUMO

Epigenetic modifications based on DNA methylation can rapidly improve the potential of corals to adapt to environmental pressures by increasing their phenotypic plasticity, a factor important for scleractinian corals to adapt to future global warming. However, the extent to which corals develop similar adaptive mechanisms and their specific adaptation processes remain unclear. Here, to reveal the regulatory mechanism by which DNA methylation improves thermal tolerance in Pocillopora damicornis under fluctuating environments, we analyzed genome-wide DNA methylation signatures in P. damicornis and compared the differences in the methylation and transcriptional responses of P. damicornis from fluctuating and stable environments using whole-genome bisulfite sequencing and nanopore-based RNA sequencingtranscriptome sequencing. We discovered low methylation levels in P. damicornis (average methylation 4.14%), with CpG accounting for 74.88%, CHH for 13.27%, and CHG for 11.85% of this methylation. However, methylation levels did not change between coral samples from the fluctuating and stable environments. The varied methylation levels in different regions of the gene revealed that the overall methylation level of the gene body was relatively high and showed a bimodal methylation pattern. Methylation occurs primarily in exons rather than introns within the gene body In P. damicornis, there was only a weak correlation between methylation and transcriptional changes at the individual gene level, and the methylation and gene expression levels generally exhibited a bell-shaped relationship, which we speculate may be due to the specificity of cnidarian species. Correlation analysis between methylation levels and the transcriptome revealed that the highest proportion of the top 20 enriched KEGG pathways was related to immunity. Additionally, P. damicornis collected from a high-temperature pool had a lower metabolic rate than those collected from a low-temperature pool. We hypothesize that the dynamic balance of energy-expenditure costs between immunity and metabolism is an important strategy for increasing P. damicornis tolerance. The fluctuating environment of high-temperature pools may increase the heat tolerance in corals by increasing their immunity and thus lowering their metabolism.


Assuntos
Antozoários , Animais , Antozoários/fisiologia , Adaptação Fisiológica , Aquecimento Global , Aclimatação/genética , Recifes de Corais
10.
J Transl Med ; 21(1): 923, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124204

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is poorly treated due to the presence of an inhibitory immune microenvironment. Tumor-associated macrophages (TAM) are an important component of TME. ALOX5 is an important lipid metabolism enzyme in cancer progression, but the mechanism by which it regulates TAM to promote ICC progression is unknown. The aim of this study was to investigate the potential mechanism of TAM regulation by ALOX5 and the translational effect of targeting ALOX5. METHODS: In this study, we investigated the association between the spatial localization of epithelial cells and TAMs by combining scRNA-seq analysis with multiplex immunofluorescence analysis. Through bulk sequencing analysis and spatial analysis, lipid metabolism genes closely related to TAM infiltration were screened. In vitro co-culture model was constructed to verify that ALOX5 and its downstream metabolite LTB4 promote M2 macrophage migration. Bulk sequencing after co-culture combined with single-cell analysis was performed to identify key pathways for up-regulation of M2 macrophage migration. Finally, the effect of CSF1R inhibitor (PLX3397) combined with ALOX5 inhibitor (Zileuton) in vivo was investigated by by xenograft tumor formation experiment in nude mice. RESULTS: ALOX5 in ICC cells was a key lipid metabolism gene affecting the infiltration of M2 macrophages in TME. Mechanically, LTB4, a metabolite downstream of ALOX5, recruited M2 macrophages to migrate around tumor cells by binding to BLT1/BLT2 and activating the PI3K pathway, which ultimately lead to the promotion of ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor effectively reduced tumor volume and M2 macrophage infiltration abundance. CONCLUSION: In ICC, LTB4, a metabolite secreted by ALOX5 of epithelial cells, binded to BLT1/BLT2 on TAM surface to activate PI3K pathway and promote TAM migration, thus promoting ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor for ICC is a promising combination therapy modality.


Assuntos
Colangiocarcinoma , Fosfatidilinositol 3-Quinases , Animais , Camundongos , Humanos , Macrófagos Associados a Tumor , Camundongos Nus , Leucotrieno B4 , Colangiocarcinoma/genética , Microambiente Tumoral , Linhagem Celular Tumoral , Araquidonato 5-Lipoxigenase
11.
Elife ; 122023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38131294

RESUMO

Background: Emerging data have supported the immunostimulatory role of radiotherapy, which could exert a synergistic effect with immune checkpoint inhibitors (ICIs). With proven effective but suboptimal effect of ICI and chemotherapy in triple-negative breast cancer (TNBC), we designed a pilot study to explore the efficacy and safety of neoadjuvant stereotactic body radiotherapy (SBRT) plus adebrelimab and chemotherapy in TNBC patients. Methods: Treatment-naïve TNBC patients received two cycles of intravenous adebrelimab (20 mg/kg, every 3 weeks), and SBRT (24 Gy/3 f, every other day) started at the second cycle, then followed by six cycles of adebrelimab plus nab-paclitaxel (125 mg/m² on days 1 and 8) and carboplatin (area under the curve 6 mg/mL per min on day 1) every 3 weeks. The surgery was performed within 3-5 weeks after the end of neoadjuvant therapy. Primary endpoint was pathological complete response (pCR, ypT0/is ypN0). Secondary endpoints included objective response rate (ORR), residual cancer burden (RCB) 0-I, and safety. Results: 13 patients were enrolled and received at least one dose of therapy. 10 (76.9%) patients completed SBRT and were included in efficacy analysis. 90% (9/10) of patients achieved pCR, both RCB 0-I and ORR reached 100% with three patients achieved complete remission. Adverse events (AEs) of all-grade and grade 3-4 occurred in 92.3% and 53.8%, respectively. One (7.7%) patient had treatment-related serious AEs. No radiation-related dermatitis or death occurred. Conclusions: Adding SBRT to adebrelimab and neoadjuvant chemotherapy led to a substantial proportion of pCR with acceptable toxicities, supporting further exploration of this combination in TNBC patients. Funding: None. Clinical trial number: NCT05132790.


Assuntos
Radiocirurgia , Neoplasias de Mama Triplo Negativas , Humanos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Terapia Neoadjuvante/efeitos adversos , Projetos Piloto , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/radioterapia
12.
Am J Cancer Res ; 13(10): 4794-4802, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970343

RESUMO

Patients with radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) are resistant to radioactive iodine-131(131I) treatment, and the clinical treatment for these patients is complex. The implantation of iodine-125 (125I) seeds in the lesion has been successfully applied to treat malignant tumors, but there are few reports on using 125I particles in the treatment of RAIR-DTC. This retrospective study collected data of 92 patients with RAIR-DTC. Patients treated with sorafenib were included in a control group (50 cases with 72 lesions) and patients treated with 125I implantation were included in an observation group (42 cases with 68 lesions). The results showed that compared with those in the control group, the lesion volume was lower and the VVR was higher in the observation group (P<0.05). The Tg and Tg-Ab levels 6 months after treatment were lower than those before treatment in both groups, and the post-treatment Tg and Tg-Ab levels of the observation group were lower than those of the control group (P<0.05). The efficacy, disease control rate, and objective remission rate were not significantly different between the observation group and the control group (P>0.05). Overall survival of patients in the observation group was longer than that in the control group, χ2 = 4.430, P = 0.035. The incidence of total adverse reactions in the observation group was lower than that in the control group (P<0.05). In conclusion, 125I seed implantation is effective in RAIR-DTC treatment as it can prolong the overall survival of patients while maintaining a safe profile.

13.
Microbiol Spectr ; 11(6): e0053123, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37861344

RESUMO

IMPORTANCE: This study comprehensively examined the community dynamics, functional profiles, and interactions of the microbiome in the world's deepest blue hole. The findings revealed a positive correlation between the α-diversities of Symbiodiniaceae and archaea, indicating the potential reliance of Symbiodiniaceae on archaea in an extreme environment resulting from a partial niche overlap. The negative association between the α-diversity and ß-diversity of the bacterial community suggested that the change rule of the bacterial community was consistent with the Anna Karenina effects. The core microbiome comprised nine microbial taxa, highlighting their remarkable tolerance and adaptability to sharp environmental gradient variations. Bacteria and archaea played significant roles in carbon, nitrogen, and sulfur cycles, while fungi contributed to carbon metabolism. This study advanced our understanding of the community dynamics, response patterns, and resilience of microorganisms populating the world's deepest blue hole, thereby facilitating further ecological and evolutional exploration of microbiomes in diverse extreme environments.


Assuntos
Microbiota , Bactérias , Archaea , Filogenia , Carbono/metabolismo
14.
Cell Mol Life Sci ; 80(11): 336, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37897511

RESUMO

Hepatitis B virus (HBV) infection is a major public health problem worldwide, causing nearly one million deaths annually. OTUD5 is a deubiquitinase associated with cancer development and innate immunity response. However, the regulatory mechanisms of OTUD5 underlying HBV replication need to be deeply elucidated. In the present investigation, we found that HBV induced significant up-regulation of OTUD5 protein in HBV-infected cells. Further study showed that OTUD5 interacted with HBV core/precore, removing their K48-linked ubiquitination chains and protecting their stability. Meanwhile, overexpression of OTUD5 could inhibit the MAPK pathway and then increase the expression of HNF4ɑ, and ERK1/2 signaling was required for OTUD5-mediated activation of HNF4α, promoting HBV replication. Together, these data indicate that OTUD5 could deubiquitinate HBV core protein degradation by its deubiquitinase function and promote HBV activity by up-regulating HNF4α expression via inhibition of the ERK1/2 pathway. These results might present a novel therapeutic strategy against HBV infection.


Assuntos
Vírus da Hepatite B , Hepatite B , Humanos , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno , Células Hep G2 , Ubiquitinação , Replicação Viral , Enzimas Desubiquitinantes/genética
15.
Drug Discov Ther ; 17(5): 328-339, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37743521

RESUMO

Lipid metabolism plays an important role in the growth and development of tumors. However, the role of lipid metabolism in gallbladder cancer (GBC) has not been clearly clarified. Here, we demonstrated that fatty acid synthase (FASN), a key enzyme in de novo fatty acid biosynthesis, had upregulated expression in GBC samples both at protein and mRNA levels. Analysis of clinical data indicated the association between elevated FASN expression and poorer histology grades. Furthermore, FASN activity impairment through FASN knockdown or treatment with orlistat resulted in the inhibition of cell proliferation and migration, as well as increased sensitivity to gemcitabine. Both FASN knockdown and orlistat treatment induced cell apoptosis. Mechanistically, impairment of FASN activity suppressed the activation of the PI3K/AKT signaling pathway, which led to increased cell apoptosis and sensitivity to gemcitabine. These findings were also validated through nude mouse xenograft models, thus highlighting the potential of targeting FASN as a clinical treatment strategy. Collectively, the present study underscores the crucial role of FASN in the progression of gallbladder cancer via the PI3K/AKT pathway.


Assuntos
Neoplasias da Vesícula Biliar , Animais , Camundongos , Humanos , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/genética , Gencitabina , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/genética , Orlistate , Ácido Graxo Sintases , Camundongos Nus , Ácido Graxo Sintase Tipo I/genética
16.
J Exp Clin Cancer Res ; 42(1): 225, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658402

RESUMO

Tumors have evolved in various mechanisms to evade the immune system, hindering the antitumor immune response and facilitating tumor progression. Immunotherapy has become a potential treatment strategy specific to different cancer types by utilizing multifarious molecular mechanisms to enhance the immune response against tumors. Among these mechanisms, the ubiquitin-proteasome system (UPS) is a significant non-lysosomal pathway specific to protein degradation, regulated by deubiquitinating enzymes (DUBs) that counterbalance ubiquitin signaling. Ubiquitin-specific proteases (USPs), the largest DUB family with the strongest variety, play critical roles in modulating immune cell function, regulating immune response, and participating in antigen processing and presentation during tumor progression. According to recent studies, the expressions of some USP family members in tumor cells are involved in tumor immune escape and immune microenvironment. This review explores the potential of targeting USPs as a new approach for cancer immunotherapy, highlighting recent basic and preclinical studies investigating the applications of USP inhibitors. By providing insights into the structure and function of USPs in cancer immunity, this review aims at assisting in developing new therapeutic approaches for enhancing the immunotherapy efficacy.


Assuntos
Imunoterapia , Neoplasias , Humanos , Citoplasma , Complexo de Endopeptidases do Proteassoma , Ubiquitina , Proteases Específicas de Ubiquitina , Neoplasias/terapia
17.
Sci Total Environ ; 903: 166439, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-37604380

RESUMO

The large seasonal temperature fluctuations caused by global warming and frequent marine heatwaves pose new challenges to survival of relatively high-latitude marginal reef corals. However, the adaptation strategies of high-latitude marginal corals are not fully understood. We employed integrated approach to investigate the response mechanism of hosts, Symbiodiniaceae, and symbiotic bacteria of marginal reef corals Acropora pruinosa and Pavona decussate in response to large seasonal temperature fluctuations. The coral holobiont maintained a high level of immunity to adapt to seasonal pressure by increasing Symbiodiniaceae energy supply. The symbiotic Symbiodiniaceae of two coral was dominated by C1 subgroup, and was stable across seasons. The α-diversity of symbiotic bacteria P. decussata and A. pruinosa in summer was higher than that in winter. The symbiotic bacterial community of two coral reorganized during different seasons. Scleractinian corals improve adaptability to seasonal stress by increasing energy supply to maintain high levels of immunity, increasing symbiotic bacterial α-diversity, and changing dominant bacteria. This study demonstrates the adaptation strategies of marginal reef corals to seasonal temperature fluctuations and provides novel insights into the study of the adaptation of corals and relatively high-latitude coral refuges in the context of global warming and intensified marine heatwaves.

18.
World J Psychiatry ; 13(7): 486-494, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37547735

RESUMO

BACKGROUND: Differentiated thyroid cancer (DTC) often seriously impacts patients' lives. Radionuclide Iodine-131 (131I) is widely used in treating patients with DTC. However, most patients know little about radionuclide therapy, and the treatment needs to be performed in a special isolation ward, which can cause anxiety and depression. AIM: To explore anxiety and depression status and their influencing factors after 131I treatment in patients with DTC. METHODS: A questionnaire survey was conducted among postoperative patients with DTC who received 131I treatment at our hospital from June 2020 to December 2022. General patient data were collected using a self-administered demographic characteristics questionnaire. The self-rating depression scale and self-rating anxiety scale were used to determine whether patients were worried about their symptoms and the degree of anxiety and depression. The patients were cate-gorized into anxiety, non-anxiety, depression, and non-depression groups. Single-variable and multiple-variable analyses were used to determine the risk factors for anxiety and depression in patients with thyroid cancer after surgery. RESULTS: A total of 144 patients were included in this study. The baseline mean score of self-rating anxiety and depression scales were 50.06 ± 16.10 and 50.96 ± 16.55, respectively. Notably, 48.62% (70/144) had anxiety and 47.22% (68/144) of the patients had depression. Sex, age, education level, marital status, household income, underlying diseases, and medication compliance significantly differed among groups (P < 0.05). Furthermore, multivariate logistic regression analysis showed that education level, per capita monthly household income, and medication compliance level affected anxiety (P = 0.015, 0.001, and 0.001 respectively. Patient's sex, marital status, and underlying diseases affected depression (P = 0.007, 0.001, and 0.009, respectively). CONCLUSION: Nursing interventions aiming at reducing the risk of anxiety and depression should target unmarried female patients with low education level, low family income, underlying diseases, and poor adherence to medications.

19.
J Cancer Res Clin Oncol ; 149(16): 14535-14547, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37567986

RESUMO

OBJECTIVE: We aimed to investigate the predictive value of pre-treatment 18F-FDG PET/CT multi-metabolic parameters and tumor metabolic heterogeneity for gastric cancer prognosis. METHODS: Seventy-one patients with gastric cancer were included. All patients underwent 18F-FDG PET/CT whole-body scans prior to treatment and had pathologically confirmed gastric adenocarcinomas. Each metabolic parameter, including SUVmax, SUVmean, MTV, and TLG, was collected from the primary lesions of gastric cancer in all patients, and the slope of the linear regression between the MTV corresponding to different SUVmax thresholds (40% × SUVmax, 80% × SUVmax) of the primary lesions was calculated. The absolute value of the slope was regarded as the metabolic heterogeneity of the primary lesions, expressed as the heterogeneity index HI-1, and the coefficient of variance of the SUVmean of the primary lesions was regarded as HI-2. Patient prognosis was assessed by PFS and OS, and a nomogram of the prognostic prediction model was constructed, after which the clinical utility of the model was assessed using DCA. RESULTS: A total of 71 patients with gastric cancer, including 57 (80.3%) males and 14 (19.7%) females, had a mean age of 61 ± 10 years; disease progression occurred in 27 (38.0%) patients and death occurred in 24 (33.8%) patients. Multivariate Cox regression analysis showed that HI-1 alone was a common independent risk factor for PFS (HR: 1.183; 95% CI: 1.010-1.387, P < 0.05) and OS (HR: 1.214; 95% CI: 1.016-1.450, P < 0.05) in patients with gastric cancer. A nomogram created based on the results of Cox regression analysis increased the net clinical benefit for patients. Considering disease progression as a positive event, patients were divided into low-, intermediate-, and high-risk groups, and Kaplan-Meier survival analysis showed that there were significant differences in PFS among the three groups. When death was considered a positive event and patients were included in the low- and high-risk groups, there were significant differences in OS between the two groups. CONCLUSION: The heterogeneity index HI-1 of primary gastric cancer lesions is an independent risk factor for patient prognosis. A nomogram of prognostic prediction models constructed for each independent factor can increase the net clinical benefit and stratify the risk level of patients, providing a reference for guiding individualized patient treatment.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Gástricas , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Neoplasias Gástricas/diagnóstico por imagem , Prognóstico , Progressão da Doença , Estudos Retrospectivos , Carga Tumoral , Compostos Radiofarmacêuticos
20.
J Cancer Res Clin Oncol ; 149(13): 12013-12024, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37421461

RESUMO

PURPOSE: To construct a nomogram for hepatocellular carcinoma (HCC) patients base on HCC-GRIm score. METHODS: Clinical cases of HCC patients diagnosed at Hunan Integrated Traditional Chinese and Western Medicine Hospital were included, and these were randomly divided into the training cohort (n = 219) and the validation cohort (n = 94), and those patients were divided into low GRIm-Score group (scores 0, 1, and 2) and high GRIm-Score group (scores 3, 4, and 5). In the training cohort, independent risk factors were determined by Cox regression analysis, and a nomogram was constructed by independent risk factors. The efficiency and the clinical applicability of nomograms were evaluated using ROC curves, calibration plot, and the decision curve (DCA), and the patients were divided into high-risk, middle-risk, and low-risk groups according to total score of nomogram. RESULTS: Compared to low HCC-GRIm score group, high HCC-GRIm score group with BCLC stage is more advanced (P < 0.001), and fewer patients received TACE (P = 0.005) and surgical treatment (P = 0.001). There was higher rate of the presence of vascular invasion (P < 0.001) and distant metastasis (P < 0.001). Multivariate Cox regression analysis screened 4 independent risk factors to construct a nomogram of HCC patients, including HCC-GRIm score, BCLC stage, albumin-to-globulin ratio (AGR), and glutamyl trans-peptidase (GGT). The consistency index (C-index) of the nomogram of the training was 0.843 (0.832-0.854) and the validation was 0.870 (0.856-0.885). The time-dependent parameter showed the AUC values of the training cohort at 1, 3, and 5 years were 0.954 (95% CI 0.929-0.980), 0.952 (95% CI 0.919-0.985), and 925 (95% CI 0.871-0.979), while the AUC values of validation cohort at 1, 3, and 5 years were 0.974 (95% CI 0.950-0.998), 0.965 (95% CI 0.931-0.999), and 0.959 (95% CI 0.898-1.021). The calibration plot showed the nomogram fits well onto perfect curves, and the DCA curve showed the net benefit of the nomogram at a certain probability threshold is significantly higher than the net benefit of the BCLC stage at the same threshold probability. Finally, all patients were divided into high-risk, middle-risk, and low-risk groups based on the total score of nomogram, and it showed effectively to identify high-risk patients. CONCLUSION: The nomogram constructed by the independent risk factors can predict the prognosis of HCC patients, providing an effective tool with clinical workers to evaluate the prognosis and survival time of HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Nomogramas , Neoplasias Hepáticas/patologia , Prognóstico , Fatores de Risco
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