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1.
Front Surg ; 8: 675661, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778352

RESUMO

Background: The aim of this study based on log odds of positive lymph nodes (LODDS) is to develop and validate an effective prognostic nomogram for patients with T3 and T4 gallbladder cancer (GBC) after resection. Patients and Methods: A total of 728 T3 and T4 gallbladder cancer patients after resection from the Surveillance, Epidemiology, and End Results (SEER) database, randomly divided into training cohort and validation cohort according to 7:3. Another 128 patients from The Second Affiliated Hospital of Nanchang University for external validation. The nomograms were built by the Cox regression model and the Fine and Grey's model. Concordance index (C-index), calibration curve and the area under receiver operating characteristic (ROC) curve (AUC) were used to evaluate the nomogram and internal verification. The decision curve analysis (DCA) was used to measure clinical applicability. Result: LODDS was independent prognostic predictor for overall survival (OS) and cancer-specific survival (CSS), and established the nomograms on this basis. The nomogram we have established has a good evaluation effect, with a C-index of 0.719 (95%CI, 0.707-0.731) for OS and 0.747 (95%CI, 0.733-0.760) for CSS. The calibration curves of OS and CSS both showed good calibration capability, and the AUC for predicting 1-, 2-, and 3-year 0.858, 0.848 were and 0.811 for OS, and 0.794, 0.793, and 0.750 for CSS. The DCA of nomograms both showed good clinical applicability. Conclusion: The nomogram can provide effective OS and CSS prediction for patients with advanced gallbladder cancer after surgery.

2.
Sci Rep ; 11(1): 19995, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620919

RESUMO

In order to improve the detection efficiency and accuracy of microfluidic chip, a magnetic beads preset technology were designed by using double permanent magnets as external magnetic field and the motion characteristics of preset magnetic beads were studied. The control principle of magnetic beads preset technology was introduced in detail, and the control structure was designed. The coupled field characteristics for magnetic beads in microchannels were analyzed, and the motion models of magnetic beads were established based on the magnetic beads preset technology, including capture motion and mixing motion. The relationship between the magnetic field force and the flow velocity for capturing magnetic bead, and the mixing time under the influence of flow field and magnetic field were derived. The magnetic beads preset technology effect was verified by experiments and numerical simulations were developed to analyze the influence of aspect ratio of permanent magnet on magnetic field. The study showed that the accuracy and efficiency of the magnetic bead control in the microchannel could be better realized by the magnetic beads preset technology. The derivation of the magnetic bead motion model can understand the motion characteristics of the magnetic bead more clearly, facilitate accurate control of the magnetic bead, and improve the success rate of the microfluidic detection.

3.
J Healthc Eng ; 2021: 1521013, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512932

RESUMO

Background: Known as an autoimmune glomerular disease, idiopathic membranous nephropathy (IMN) is considered to be associated with phospholipase A2 receptor (PLA2R) in terms of the main pathogenesis. The quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies by time-resolved fluoroimmunoassay (TRFIA) was determined, and the value of them, both in the clinical prediction of risk stratification in IMN, was observed in this study. Methods: 95 patients with IMN proved by renal biopsy were enrolled, who had tested positive for serum PLA2R antibodies by ELISA, and the quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies was achieved by TRFIA. All the patients were divided into low-, medium-, and high-risk groups, respectively, which were set as dependent variables, according to proteinuria and renal function. Random forest (RF) was used to estimate the value of serum PLA2R-IgG and PLA2R-IgG4 in predicting the risk stratification of progression in IMN. Results: Out-of-bag estimates of variable importance in RF were employed to evaluate the impact of each input variable on the final classification accuracy. The variable of albumin, PLA2R-IgG, and PLA2R-IgG4 had high values (>0.3) of 0.3156, 0.3981, and 0.7682, respectively, which meant that these three were more important for the risk stratification of progression in IMN. In order to further assess the contribution of PLA2R-IgG and PLA2R-IgG4 to the model, we built four different models and found that PLA2R-IgG4 played an important role in improving the predictive ability of the model. Conclusions: In this study, we established a random forest model to evaluate the value of serum PLA2R-IgG4 antibodies in predicting risk stratification of IMN. Compared with PLA2R-IgG, PLA2R-IgG4 is a more efficient biomarker in predicting the risk of progression in IMN.

4.
ACS Appl Mater Interfaces ; 13(37): 44488-44496, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34514775

RESUMO

Light-driven polymerization, such as photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization, enables biological benign conditions and versatile functional polymer structure design, which is readily used in protein-polymer bioconjugates. However, conventional metalloporphyrinic homogeneous catalysts for PET-RAFT polymerization suffer from limited aqueous solubility and tedious purification. Here we demonstrate the design of PET-RAFT photocatalyst from the reticular assembled Zr-porphyrinic metal-organic frameworks (MOFs), along with a biomacromolecule-based chain transfer agent, as efficient bioconjugation tools in water. Our methodology offers manufacturing advantages on bioconjugates under mild conditions such that MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and cytotoxicity assays have shown the preservation of the protein integrity, bioactivity, and high cell viability after PET-RAFT polymerization. We find that the fast kinetics are benefiting from the ultrahigh loading of metalloporphyrins in MOF-525-Zn. This heterogeneous catalyst also allows us to maintain living characteristics to incorporate myriads of monomers into block copolymers. Other advantages like easy postreaction purification, reusability, and high oxygen tolerance even in an open system are demonstrated. This study provides a tool of highly efficient heterogeneous photocatalysts for polymer-protein bioconjugation in aqueous media and paves the road for biological applications.

5.
J Hematol Oncol ; 14(1): 152, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556152

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy has shown tremendous success in eradicating hematologic malignancies. However, this success has not yet been extrapolated to solid tumors due to the limited infiltration and persistence of CAR-T cells in the tumor microenvironment (TME). In this study, we screened a novel anti-CD70 scFv and generated CD70 CAR-T cells that showed effective antitumor functions against CD70+ renal carcinoma cells (RCCs) both in vitro and in vivo. We further evaluated the effect and explored the molecular mechanism of a PARP inhibitor (PARPi) in CAR-T cell immunotherapy by administering the PARPi to mouse xenografts model derived from human RCC cells. Treatment with the PARPi promoted CAR-T cell infiltration by stimulating a chemokine milieu that promoted CAR-T cell recruitment and the modulation of immunosuppression in the TME. Moreover, our data demonstrate that PARPi modulates the TME by activating the cGAS-STING pathway, thereby altering the balance of immunostimulatory signaling and enabling low-dose CAR-T cell treatment to induce effective tumor regression. These data demonstrate the application of CD70 CAR-T cell therapeutic strategies for RCC and the cross-talk between targeting DNA damage responses and antitumor CAR-T cell therapy. These findings provide insight into the mechanisms of PARPis in CAR-T cell therapy for RCC and suggest a promising adjuvant therapeutic strategy for CAR-T cell therapy in solid tumors.


Assuntos
Ligante CD27/antagonistas & inibidores , Carcinoma de Células Renais/terapia , Imunoterapia Adotiva/métodos , Neoplasias Renais/terapia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Anticorpos de Cadeia Única/uso terapêutico , Animais , Ligante CD27/imunologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Proteínas de Membrana/imunologia , Camundongos , Nucleotidiltransferases/imunologia , Transdução de Sinais
6.
Micromachines (Basel) ; 12(7)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34357224

RESUMO

Breast disease is one of the critical diseases that plague females, as is known, breast cancer has high mortality, despite significant pathophysiological progress during the past few years. Novel diagnostic and therapeutic approaches are needed to break the stalemate. An organ-on-chip approach is considered due to its ability to repeat the real conditions found in the body on microfluidic chips, offsetting the shortcomings of traditional 2D culture and animal tests. In recent years, the organ-on-chip approach has shown diversity, recreating the structure and functional units of the real organs/tissues. The applications were also developed rapidly from the laboratory to the industrialized market. This review focuses on breast tumor-on-a-chip approaches concerning the diversity models and applications. The models are summarized and categorized by typical biological reconstitution, considering the design and fabrication of the various breast models. The breast tumor-on-a-chip approach is a typical representative of organ chips, which are one of the precedents in the market. The applications are roughly divided into two categories: fundamental mechanism research and biological medicine. Finally, we discuss the prospect and deficiencies of the emerging technology. It has excellent prospects in all of the application fields, however there exist some deficiencies for promotion, such as the stability of the structure and function, and uniformity for quantity production.

7.
Anim Biosci ; 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34237933

RESUMO

Objective: FKBP5 has been shown to play an important role in metabolically active tissues such as skeletal muscle. However, the expression of FKBP5 in Muscovy duck tissues and its association with body weight are still unclear. Methods: In this study, qRT-PCR was used to detect the expression of FKBP5 in different tissues of Muscovy duck at different growth stages. Further, SNPs were detected in the exon region of FKBP5 and were combined analyzed with the body weight of 334 Muscovy ducks. Results: FKBP5 was highly expressed in various tissues of Muscovy duck at days 17, 19, 21, 24 and 27 of embryonic development. In addition, the expression of FKBP5 in the tissues of female adult Muscovy ducks was higher than that of male Muscovy ducks. Besides, an association analysis indicated that 3 SNPs were related to body weight trait. At the g.4819252 A>G, the body weight of AG genotype was significantly higher than that of the AA and the GG genotype. At the g.4821390 G>A, the genotype GA was extremely significantly related to body weight. At the g.4830622 T>G, the body weight of TT was significantly higher than GG and TG. Conclusion: These findings indicate the possible effects of expression levels in various tissues and the SNPs of FKBP5 on Muscovy duck body weight trait. FKBP5 could be used as molecular marker for muscle development trait using early marker-assisted selection (MAS) of Muscovy ducks.

8.
Clin Biochem ; 96: 49-55, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34252448

RESUMO

BACKGROUND: The renal biopsy is an accurate and reliable gold standard for membranous nephropathy (MN) diagnosis. However, it is an invasive procedure involving the risk of hemorrhage or infection. Thus, an alternative approach that can facilitate the effective diagnosis and treatment monitoring of idiopathic membranous nephropathy (IMN) is urgently needed. METHODS: We established a dual-labeled time-resolved fluoroimmunoassay (TRFIA) to simultaneously detect phospholipase A2 receptor (PLA2R)-IgG4 and PLA2R-IgG antibodies. Utilizing this assay, we determined the ratio of autoantibodies in the serum of patients with different kidney diseases and normal controls. RESULTS: The sensitivity of TRFIA for detecting anti-PLA2R-IgG and anti-PLA2R-IgG4 was 0.12 µg/mL and 0.001 µg/mL, respectively. Human IgA did not interfere with the assay. Compared to anti-PLA2R-IgG alone, the positive rate of IMN could be increased from 86.5 % to 91.7 % through the combined use of anti-PLA2R-IgG4 and the PLA2R-IgG4/IgG ratio. In contrast, the false-positive rates for the detection of IgA nephropathy, lupus nephropathy, diabetic nephropathy, and minimal change nephropathy decreased from 25 to 50 % to 0 %. CONCLUSIONS: The dual-labeled PLA2R-IgG4/IgG-TRFIA for simultaneous detection of anti-PLA2R-IgG4 and anti-PLA2R-IgG will contribute to improved accuracy of IMN diagnosis.


Assuntos
Autoanticorpos/sangue , Glomerulonefrite Membranosa/sangue , Imunoglobulina G/sangue , Receptores da Fosfolipase A2/sangue , Fluorimunoensaio , Glomerulonefrite Membranosa/diagnóstico , Humanos , Sensibilidade e Especificidade
9.
Radiat Environ Biophys ; 60(3): 475-483, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34191096

RESUMO

Several studies have reported inconsistent results about second primary lung cancer (SPLC) after irradiation for initial primary lung cancer (IPLC). The present study aims to assess the effect of ionising radiation on the risk of SPLC. The study population came from SEER database, and included a population-based cohort of 21,397 individuals diagnosed with IPLC between 2004 and 2009 who survived more than 7 years after the initial diagnosis. The first aim was to estimate the risk of SPLC in different periods and the cumulative risk of SPLC. Subsequently, a generalized additive model with Poisson regression analysis and a proportional sub-distribution hazard model was used to determine whether radiation affected the risk of SPLC. Until Dec 2016, there were 488 individuals who developed SPLC, 5368 individuals who died, and there were 15,541 alive individuals, respectively. The risk of SPLC was found to gradually decline with the extent of follow-up time. Age and histology were the two main risk factors of developing SPLC in Poisson regression and competing risk analyses. In Poisson regression analysis, radiation had no significant effect on the risk of developing SPLC (adjusted OR = 0.80, 95% CI 0.54, 1.19, P = 0.28). When considered competing risk of all-cause death, the risk of SPLC in the radiation group was similar to that in the non-radiation group (adjusted sHR = 0.80, 95% CI 0.56, 1.13, P = 0.21). The risk of SPLC was different during different follow-up time. Irradiation for IPLC seemingly did not affect the risk of developing SPLC.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Segunda Neoplasia Primária/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Risco
10.
Biomolecules ; 11(5)2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066020

RESUMO

Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) in patients with HRR-deficient tumors and that PARPis can improve the mortality rate of PC in patients with BRCA1/2 mutations through a synthetic lethality. Olaparib has been approved by the FDA for advanced ovarian and breast cancer with BRCA mutations, and as a maintenance therapy for ovarian cancer after platinum chemotherapy. PARPis are also a new and emerging clinical treatment for metastatic castration-resistant prostate cancer (mCRPC). Although PARPis have shown great efficacy, their widespread use is restricted by various factors, including drug resistance and the limited population who benefit from treatment. It is necessary to study the combination of PARPis and other therapeutic agents such as anti-hormone drugs, USP7 inhibitors, BET inhibitors, and immunotherapy. This article reviews the mechanism of PARP inhibition in the treatment of PC, the progress of clinical research, the mechanisms of drug resistance, and the strategies of combination treatments.


Assuntos
Antineoplásicos/uso terapêutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Reparo do DNA , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases/química , Neoplasias da Próstata/tratamento farmacológico , Ensaios Clínicos como Assunto , Humanos , Masculino , Poli(ADP-Ribose) Polimerases/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
11.
Anal Methods ; 13(27): 3017-3023, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34164636

RESUMO

BACKGROUND: the level of serum antibodies against the M-type phospholipase A2 receptor (anti-PLA2R-IgG) is closely related to the disease activity of idiopathic membranous nephropathy (IMN). Therefore, the establishment of a sensitive and rapid method for detecting anti-PLA2R-IgG will be beneficial for the differential diagnosis of IMN. METHODS: magnetic microspheres coupled with the PLA2R antigen were used to capture anti-PLA2R-IgG in serum samples, and europium-labeled goat anti-human IgG antibodies were used for tracking. An anti-PLA2R-IgG-time-resolved fluoroimmunoassay (TRFIA) based on magnetic microspheres using an indirect method was established and analyzed. Various indicators of this method were evaluated. RESULTS: the sensitivity of the anti-PLA2R-IgG-TRFIA based on magnetic microspheres was 0.51 RU mL-1, and the linear detection range was 0.51-1000 RU mL-1. The average intra- and inter-assay coefficients of variation (CVs) were 3.62% and 4.45%, respectively, and the average recovery was 95.60%. No cross-reactivity with IgA was observed. The median (interquartile range) concentration of anti-PLA2R-IgG in patients with IMN was 40.37 RU mL-1 (11.33 to 83.05 RU mL-1). The cut-off values of the anti-PLA2R-IgG concentration for healthy volunteers and those with other kidney diseases were determined to be 8.06 RU mL-1 and 13.23 RU mL-1, respectively. Additionally, the positive rates of anti-PLA2R-IgG in patients with IMN corresponding to the above cut-off values were 91.07% and 71.32%, respectively. The correlation coefficient between the magnetic microsphere-based anti-PLA2R-TRFIA and the PLA2R-ELISA kit for detecting anti-PLA2R-IgG was 0.944. CONCLUSION: a highly sensitive and rapid magnetic microsphere-based anti-PLA2R-IgG-TRFIA was successfully established to detect the concentrations of anti-PLA2R-IgG in the sera of patients with IMN.


Assuntos
Autoanticorpos , Receptores da Fosfolipase A2 , Fluorimunoensaio , Humanos , Fenômenos Magnéticos , Microesferas
12.
Clin Chim Acta ; 521: 34-39, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34144042

RESUMO

BACKGROUND: We evaluated the use of thyroid stimulating immunoglobulin (TSI) assay to optimize the detection strategy for Graves' disease. METHODS: Five hundred and forty-four well characterized serum samples from the Clinical Laboratory of Shanghai Tongren Hospital were collected from August 2019 to April 2020. The serum samples were obtained from 52 untreated GD patients, 155 treated GD patients, 83 patients with Hashimoto's thyroiditis, 70 patients with thyroid nodules, 83 patients with thyroid cancer, and 101 healthy subjects. All samples were evaluated by both TSI assay and TSH receptor autoantibodies (TRAb) assay. Moreover, 23 patients without a distinct thyroid disease diagnosis at the first visit were monitored for 6 months to make a final diagnosis. RESULTS: The clinical sensitivity of the TSI and TRAb assays was 98.10% and 94.20% respectively, while the clinical specificity was 92.30% and 96.70% respectively. ROC plot analysis based on sera of UT-GD (newly diagnosed GD patients) revealed an area under the curve (AUC) of 0.974 for the TSI assay. The best cutoff value was 0.58 IU/l (98.0% of sensitivity, 92.8% of specificity). The AUC for the TRAb assay was 0.961. Furthermore, combining TSI and TRAb results, the area under the curve was 0.981. In a pilot study of 23 patients with an uncertain initial diagnosis, the follow-up results showed the clinical diagnosis of 22 out of 23 cases were resolved in agreement with the results obtained by the TSI assay, and one case matched the result obtained by TRAb assay. CONCLUSION: The TSI assay presents very promising analytical characteristics and could be adopted in clinical practice to improve GD diagnosis. The TSI assay might be better than TRAb assay in initial differential diagnosis of GD from other thyroid diseases.


Assuntos
Doença de Graves , Receptores da Tireotropina , Autoanticorpos , China , Doença de Graves/diagnóstico , Humanos , Projetos Piloto
13.
Cancer Cell Int ; 21(1): 286, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059060

RESUMO

BACKGROUND: The HSP70 family of heat shock protein plays a critical role in protein synthesis and transport to maintain protein homeostasis. Several studies have indicated that HSP70s are related to the development and occurrence of various cancers. METHODS: The relationship between the overall survival rate of hepatocellular carcinoma patients and the expression of 14 HSP70s from multiple databases, such as TCGA, ONCOMINE, cBioPortal was investigated. Western Blot and PCR were used to evaluate HSPA4 and HSPA14 expressions in various HCC cells to identify suitable cell lines for further experiments .Wound-healing assays, Transwell assays and EdU assays were used to verify the effects of HSPA4 and HSPA14 on the function of hepatocellular carcinoma cells, and statistical analysis was performed. RESULTS: Hepatocellular carcinoma tissues significantly expressed the 14 HSP70s compared to the normal samples. Besides, the high HSPA1A, HSPA1B, HSPA4, HSPA5, HSPA8, HSPA13, and HSPA14 expressions were inversely associated with the overall survival rate of patients, tumor grade, and cancer stage. A PPI regulatory network was constructed using the 14 HSP70s proteins with HSPA5 and HSPA8 at the network center. Univariate and multivariate analyses showed that HSPA4 and HSPA14 could be independent risk factors for the prognosis of hepatocellular carcinoma patients. Cell experiments have also confirmed that reducing HSPA4 and HSPA14 expressions can inhibit the invasion, metastasis, and proliferation of hepatocellular carcinoma cells. CONCLUSIONS: Therefore, the HSP70s significantly influence the occurrence and development of hepatocellular carcinoma. For instance, HSPA4 and HSPA14 can be novel therapeutic targets and prognostic biomarkers for hepatocellular carcinoma.

14.
Nat Commun ; 12(1): 3276, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078898

RESUMO

Chinese goldthread (Coptis chinensis Franch.), a member of the Ranunculales, represents an important early-diverging eudicot lineage with diverse medicinal applications. Here, we present a high-quality chromosome-scale genome assembly and annotation of C. chinensis. Phylogenetic and comparative genomic analyses reveal the phylogenetic placement of this species and identify a single round of ancient whole-genome duplication (WGD) shared by the Ranunculaceae. We characterize genes involved in the biosynthesis of protoberberine-type alkaloids in C. chinensis. In particular, local genomic tandem duplications contribute to member amplification of a Ranunculales clade-specific gene family of the cytochrome P450 (CYP) 719. The functional versatility of a key CYP719 gene that encodes the (S)-canadine synthase enzyme involved in the berberine biosynthesis pathway may play critical roles in the diversification of other berberine-related alkaloids in C. chinensis. Our study provides insights into the genomic landscape of early-diverging eudicots and provides a valuable model genome for genetic and applied studies of Ranunculales.


Assuntos
Alcaloides de Berberina/metabolismo , Coptis/genética , Sistema Enzimático do Citocromo P-450/genética , Genoma de Planta , Proteínas de Plantas/genética , Vias Biossintéticas/genética , Coptis/química , Coptis/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Anotação de Sequência Molecular , Filogenia , Proteínas de Plantas/metabolismo , Plantas Medicinais
15.
Front Surg ; 8: 659422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079814

RESUMO

Background: This study aims to establish an effective nomogram to predict the overall survival of patients with intrahepatic cholangiocarcinoma (ICC). Patients and Methods: Data used to build the nomogram comes from the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with ICC between 2005 and 2016 were retrospectively collected. Prediction accuracy and discrimination ability of the nomogram was evaluated by concordance index (C-index) and calibration curve. The area under receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA) were used to compare the precision of the 1-, 3-, and 5-year survival of the nomogram with 8th American Joint Commission on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. Finally, it was verified in a prospective study of patients diagnosed with ICC in the Second Affiliated Hospital of Nanchang University from 2013 to 2020 by bootstrap resampling. Result: The study contains two parts of data; we establish a nomogram using external data, and we conducted internal verification and external verification. The nomogram that we have established has good calibration, with a concordance index (C-index) of 0.75 (95% CI, 0.74-0.76) for overall survival (OS) prediction. The AUC value of the nomogram predicting 1-, 3-, and 5-year OS rates were 0.821, 0.828, and 0.836, which were higher than those of the 8th AJCC TNM staging systems. The calibration curve for the probability of survival between prediction by nomogram and actual observation shows good agreement. The nomogram showed better accuracy than the 8th edition AJCC TNM staging. Conclusion: The nomogram established can provide a more accurate prognosis for patients with intrahepatic cholangiocarcinoma.

16.
Cell Death Dis ; 12(6): 503, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006852

RESUMO

Apurinic/apyrimidinic endonuclease 1 (APE1) plays a critical role in the base excision repair (BER) pathway, which is responsible for the excision of apurinic sites (AP sites). In non-small cell lung cancer (NSCLC), APE1 is highly expressed and associated with poor patient prognosis. The suppression of APE1 could lead to the accumulation of unrepaired DNA damage in cells. Therefore, APE1 is viewed as an important marker of malignant tumors and could serve as a potent target for the development of antitumor drugs. In this study, we performed a high-throughput virtual screening of a small-molecule library using the three-dimensional structure of APE1 protein. Using the AP site cleavage assay and a cell survival assay, we identified a small molecular compound, NO.0449-0145, to act as an APE1 inhibitor. Treatment with NO.0449-0145 induced DNA damage, apoptosis, pyroptosis, and necroptosis in the NSCLC cell lines A549 and NCI-H460. This inhibitor was also able to impede cancer progression in an NCI-H460 mouse model. Moreover, NO.0449-0145 overcame both cisplatin- and erlotinib-resistance in NSCLC cell lines. These findings underscore the importance of APE1 as a therapeutic target in NSCLC and offer a paradigm for the development of small-molecule drugs that target key DNA repair proteins for the treatment of NSCLC and other cancers.


Assuntos
Apoptose/imunologia , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Necroptose/imunologia , Piroptose/imunologia , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus
17.
J Immunol Res ; 2021: 5548463, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33987447

RESUMO

Signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein (SAP) play important role in inflammatory and autoimmune diseases. Our study is aimed at detecting the expression of SLAM and SAP in patients with Graves' disease (GD) and analyzing the effect of SLAM/SAP on circulating blood CD4+CXCR5+Foxp3+ follicular regulatory T (Tfr) cells. The level of SAP in CD4+CXCR5+ T cells and the level of SLAM on CD19+ B cells were significantly increased in the patients with GD, but no significant difference in the level of SLAM on CD4+CXCR5+ T cells was observed between the patients with GD and the healthy controls. A decrease in the percentage of Foxp3+ cells in CD4+CXCR5+ T cells was observed following anti-SLAM treatment, but the percentages of IFN-γ + cells, IL-4+ cells, and IL-17+ cells showed no obvious differences. The proportion of circulating Tfr cells was decreased in the patients with GD, and the proportion of circulating Tfr cells had a negative correlation with the level of SAP in CD4+CXCR5+ T cells and the levels of autoantibodies in the serum of the patients with GD. Our results suggested that the SLAM/SAP signaling pathway is involved in the decrease of circulating Tfr cells in Graves' disease.

18.
J Agric Food Chem ; 69(21): 5783-5797, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34009975

RESUMO

An immunoassay is mostly employed for the direct detection of food contaminants, and a molecular assay for targeting nucleic acids employs amplification techniques for distinguishing genes. The integration of an immunoassay with nucleic acid amplification techniques inherits the direct and rapid performance of an immunoassay and the ultrasensitive merit of a molecular assay. Enthusiastic attention has been attracted in recent years on the utilization of isothermal amplification techniques in an immunoassay, as well as the employment of a lateral flow immunoassay in a molecular assay. Thus, this Review discussed these kinds of approaches from two categories: immuno-nucleic acid amplification (I-NAA) and nucleic acid amplification-immunoassay (NAA-I). The advantages, drawbacks, and future developments were discussed for a comprehensive understanding.


Assuntos
Técnicas de Amplificação de Ácido Nucleico , Ácidos Nucleicos , Bioensaio , Imunoensaio
19.
J Biol Chem ; 296: 100616, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33811857

RESUMO

The scavenger receptor class B type 1 (SR-B1), a high-density lipoprotein (HDL) receptor, is a membrane glycoprotein that mediates selective uptake of HDL-cholesterol and cholesterol ester (CE) into cells. SR-B1 is subject to posttranslational regulation; however, the underlying mechanisms still remain obscure. Here, we identified a novel SR-B1-interacting protein, GIPC1 (GAIP-interacting protein, C terminus 1) that interacts with SR-B1 and stabilizes SR-B1 by negative regulation of its proteasomal and lysosomal degradation pathways. The physiological interaction between SR-B1 and GIPC1 was supported by co-immunoprecipitation of wild-type and mutant GIPC1 constructs in SR-B1 ± GIPC1 overexpressing cells, in native liver cells, and in mouse liver tissues. Overexpression of GIPC1 increased endogenous SR-B1 protein levels, subsequently increasing selective HDL-cholesterol/CE uptake and cellular triglyceride (TG) and total cholesterol (TC) levels, whereas silencing of GIPC1 in the mouse liver was associated with blunted hepatic SR-B1 levels, elevated plasma TG and TC, and attenuated hepatic TG and TC content. A positive correlation was identified between GIPC1 and SR-B1 expression, and both expressions of GIPC1 and SR-B1 from human liver samples were inversely correlated with body mass index (BMI) from human subjects. We therefore conclude that GIPC1 plays a key role in the stability and function of SR-B1 and can also effectively regulate hepatic lipid and cholesterol metabolism. These findings expand our knowledge of the regulatory roles of GIPC1 and suggest that GIPC1 exerts a major effect on cell surface receptors such as SR-B1 and its associated hepatic lipid and cholesterol metabolic processes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antígenos CD36/química , Colesterol/metabolismo , Fígado/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Transporte Biológico , Antígenos CD36/genética , Antígenos CD36/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Estabilidade Proteica
20.
Animals (Basel) ; 11(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809502

RESUMO

Skeletal muscle, accounting for approximately 50% of body weight, is the largest and most important tissue. In this study, the gene expression profiles and pathways in skeletal muscle of Pekin duck were investigated and compared at embryonic day 17, 21, and 27 and postnatally at 6 months of age. An average of 49,555,936 reads in each sample was obtained from the transcriptome libraries. Over 70.0% of alternative splicing (AS) in each sample was mainly alternative 5' first exon (transcription start site)-the first exon splicing (TSS) and alternative 3' last exon (transcription terminal site)-the last exon splicing (TTS), indicating that TSS and TTS were the most common AS event in Pekin ducks, and these AS events were closely related to the regulation of muscle development at different growth stages. The results provided a valuable genomic resource for selective breeding and functional studies of genes. A total of 299 novel genes with ≥2 exons were obtained. There were 294 to 2806 differentially expressed genes (DEGs) in each pairwise comparison of Pekin duck. Notably, 90 DEGs in breast muscle and 9 DEGs in leg muscle were co-expressed at all developmental points. DEGs were validated by qPCR analysis, which confirmed the tendency of the expression. DEGs related to muscle development were involved in biological processes such as "endodermal cell differentiation", "muscle cell cellular homeostasis", "skeletal muscle tissue growth" and "skeletal muscle cell differentiation", and were involved in pathways such as oxidative phosphorylation, ECM-receptor (extracellular matrix receptor) interaction, focal adhesion, carbon metabolism, and biosynthesis of amino acids. Some DEGs, including MYL4, IGF2BP1, CSRP3, SPP1 and KLHL31, as well as LAMB2, LAMA2, ITGB1 and OPN, played crucial roles in muscle growth and development. This study provides valuable information about the expression profile of mRNAs and pathways from duck skeletal muscle at different growth stages, and further functional study of these mRNAs and pathways could provide new ideas for studying the molecular networks of growth and development in duck skeletal muscle.

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