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1.
Appl Opt ; 63(5): 1306-1312, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38437310

RESUMO

A broadband and narrowband switchable terahertz (THz) absorber based on a bulk Dirac semimetal (BDS) and strontium titanate (STO) is proposed. Narrowband and broadband absorption can be switched by adjusting the Fermi level of the BDS. When the Fermi level of the BDS is 100 meV, the device is an absorber with three narrowband absorption peaks. The frequencies are 0.44, 0.86, and 1.96 THz, respectively, when the temperature of STO is 250 K. By adjusting the temperature of STO from 250 to 500 K, the blue shifts of the frequencies are approximately 0.14, 0.32, and 0.60 THz, respectively. The sensitivities of the three absorption peaks are 0.56, 1.27, and 2.38 GHz/K, respectively. When the Fermi level of the BDS is adjusted from 100 to 30 meV, the device can be switched to a broadband absorber with a bandwidth of 0.70 THz. By adjusting the temperature of STO from 250 to 500 K, the central frequency shifts from 1.40 to 1.79 THz, and the bandwidth broadens from 0.70 to 0.96 THz. The sensitivity of the central frequency is 1.57 GHz/K. The absorber also has a wide range of potential applications in multifunctional tunable devices, such as temperature sensors, stealth equipment, and filters.

2.
J Appl Toxicol ; 43(7): 1095-1103, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36787806

RESUMO

The aim of this study was to determine the effect of tauroursodeoxycholic acid (TUDCA) on the alpha-naphthylisothiocyanate (ANIT)-induced model of cholestasis in mice. Wild-type and farnesoid X receptor (FXR)-deficient (Fxr-/- ) mice were used to generate cholestasis models by gavage with ANIT. Obeticholic acid (OCA) was used as a positive control. In wild-type mice, treatment with TUDCA for 7 days resulted in a dramatic increase in serum levels of alanine aminotransferase (ALT), with aggravation of bile infarcts and hepatocyte necrosis with ANIT-induction. TUDCA activated FXR to upregulate the expression of bile salt export pump (BSEP), increasing bile acids (BAs)-dependent bile flow, but aggravating cholestatic liver injury when bile ducts were obstructed resulting from ANIT. In contrast, TUDCA improved the liver pathology and decreased serum ALT and alkaline phosphatase (ALP) levels in ANIT-induced Fxr-/- mice. Furthermore, TUDCA inhibited the expression of cleaved caspase-3 and reduced the area of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining in the model mice. TUDCA also upregulated anion exchanger 2 (AE2) protein expression, protecting cholangiocytes against excessive toxic BAs. Our results showed that TUDCA aggravated cholestatic liver injury via the FXR/BSEP pathway when bile ducts were obstructed, although TUDCA inhibited apoptotic activity and protected cholangiocytes against excessive toxic BAs.


Assuntos
Colagogos e Coleréticos , Colestase , Camundongos , Animais , Colagogos e Coleréticos/efeitos adversos , Colagogos e Coleréticos/metabolismo , 1-Naftilisotiocianato/toxicidade , 1-Naftilisotiocianato/metabolismo , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Fígado , Colestase/induzido quimicamente , Ácidos e Sais Biliares/metabolismo
3.
Opt Express ; 30(14): 24703-24715, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-36237018

RESUMO

This letter presents a fabricated Dirac point modulator of a graphene-based terahertz electromagnetically induced transparency (EIT)-like metasurface (GrE & MS). Dynamic modulation is realized by applying three stimulus modes of optical pump, bias voltage, and optical pump-bias voltage combination. With increasing luminous flux or bias voltage, the transmission amplitude undergoes two stages: increasing and decreasing, because the graphene Fermi level shifts between the valence band, Dirac point, and conduction band. Thus, an approximate position of the Dirac point can be evaluated by the transmission spectrum fluctuation. The maximum modulation depth is measured to be 182% under 1 V. These findings provide a method for designing ultrasensitive terahertz modulation devices.

4.
Opt Express ; 30(22): 40401-40412, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36298974

RESUMO

Terahertz logic gates play a vital role in optical signal processing and terahertz digitization. Herein, a strategy to design an all-optical terahertz logic gate device composed of metamaterials with a semiconductor-metal hybrid is proposed; accordingly, a concrete logic gate composed of Ge embedded-in Au stripe supported by a Si board is presented theoretically. Simulation results reveal the dependence of the terahertz transmission spectra on the different illuminations in the device. Based on the illumination-transmission response, the designed device can realize the NOR or OR Boolean operation. The effects of the width of the Ge-Au stripe as well as the Si board on the transmission spectra and logic performance were also investigated.

5.
BMC Cancer ; 22(1): 1222, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443693

RESUMO

INTRODUCTION: Clinicians increasingly perform laparoscopic surgery for intrahepatic cholangiocarcinoma (ICC). However, this surgery can be difficult in patients with advanced-stage ICC because of the complicated procedures and difficulty in achieving high-quality results. We compared the effects of a three-step optimized procedure with a traditional procedure for patients with advanced-stage ICC. METHODS: Forty-two patients with advanced-stage ICC who received optimized laparoscopic hemihepatectomy with lymph node dissection (LND, optimized group) and 84 propensity score-matched patients who received traditional laparoscopic hemihepatectomy plus LND (traditional group) were analyzed. Surgical quality, disease-free survival (DFS), and overall survival (OS) were compared. RESULTS: The optimized group had a lower surgical bleeding score (P = 0.038) and a higher surgeon satisfaction score (P = 0.001). Blood loss during hepatectomy was less in the optimized group (190 vs. 295 mL, P < 0.001). The optimized group had more harvested LNs (12.0 vs. 8.0, P < 0.001) and more positive LNs (8.0 vs. 5.0, P < 0.001), and a similar rate of adequate LND (88.1% vs. 77.4%, P = 0.149). The optimized group had longer median DFS (9.0 vs. 7.0 months, P = 0.018) and median OS (15.0 vs. 13.0 months, P = 0.046). In addition, the optimized group also had a shorter total operation time (P = 0.001), shorter liver resection time (P = 0.001), shorter LND time (P < 0.001), shorter hospital stay (P < 0.001), and lower incidence of total morbidities (14.3% vs. 36.9%, P = 0.009). CONCLUSIONS: Our optimization of a three-step laparoscopic procedure for advanced ICC was feasible, improved the quality of liver resection and LND, prolonged survival, and led to better intraoperative and postoperative outcomes.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Laparoscopia , Humanos , Laparoscopia/efeitos adversos , Colangiocarcinoma/cirurgia , Hepatectomia/efeitos adversos , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos
6.
BMC Infect Dis ; 22(1): 236, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260103

RESUMO

BACKGROUND: Schistosoma japonicum was once one of the most severe parasitic diseases in China. After 70 years of national schistosomiasis control programmes, the prevalence and associated morbidity of the infection have been reduced to a much lower level. However, due to the low sensitivity of the current detection approaches, many minor infections in humans could not be identified and ultimately develop chronic injuries with liver abnormalities, a specific 'network' echogenic pattern under ultrasonography. Therefore, as more people take part in physical examinations, we performed this meta-analysis to estimate the overall prevalence of schistosomiasis-associated liver abnormalities in China. METHODS: The publications were searched systematically across five electronic databases. All eligible studies were assessed with quality evaluation forms. Heterogeneity of studies was determined using the I2 and Q tests. A random effects or fixed effects model was employed based on heterogeneity results. The pooled prevalence and its 95% confidence intervals were calculated with the Freeman-Tukey double arcsine transformation. All analyses were conducted using R with the "meta" package. The protocol registration number was CRD42021232982. RESULTS: A total of 19 relevant articles, including 21 studies, were included. The average score of study quality was 6.4 (total score 7), indicating high quality of all included studies. A total of 268, 247 persons were included, and 43, 917 persons were diagnosed with schistosomiasis liver abnormalities by ultrasonography. High degrees of heterogeneity existed among all studies or within subgroups. The overall pooled prevalence was 18.64% (95% CI: 11.88-26.50%). The estimate significantly increased over time and varied among provinces, with the highest in Shanghai and the lowest in Sichuan. The estimate in people aged 60 years or older was significantly higher than that in people of all ages. No significant difference was seen when based on study areas (urban or rural areas) or gender. CONCLUSION: The long-term burden of schistosomiasis in China remains large, as nearly one-fifth of the examined persons were diagnosed with schistosomiasis liver abnormalities. The pooled prevalence was associated with regions or age groups. Such may have a high reference value in the exact calculation of the disease burden and can be helpful for policy makers in prioritizing public health.


Assuntos
Schistosoma japonicum , Esquistossomose Japônica , Animais , China/epidemiologia , Humanos , Fígado/diagnóstico por imagem , Pessoa de Meia-Idade , Prevalência , Esquistossomose Japônica/diagnóstico por imagem , Esquistossomose Japônica/epidemiologia , Ultrassonografia
7.
Mol Biol Rep ; 49(1): 511-518, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34725747

RESUMO

BACKGROUND: Oncomelania hupensis hupensis is the only intermediate host of Schistosoma japonicum, the causative agent of schistosomiasis in China and is therefore of significant medical and veterinary health importance. Although tremendous progress has been achieved, there remains an understudied area of approximately 2.06 billion m2 of potential snail habitats. This area could be further increased by annual flooding. Therefore, an understanding of population genetics of snails in these areas may be useful for future monitoring and control activities. METHODS AND RESULTS: We sampled snails from Hexian (HX), Zongyang (ZY) and Shitai (ST) in Anhui (schistosomiasis transmission control), and from Hengtang (HT), Taicang (TC), Dongsan (DS) and Xisan (XS) in Jiangsu (schistosomiasis transmission interrupted), downstream of Anhui. ST, DS and XS are classified as hilly and mountainous areas, and HX, ZY, TC and HT as lake and marshland areas. The mitochondrial cytochrome c oxidase subunit I gene were sequenced. Out of 115 snails analyzed, 29 haplotypes were identified. We observed 56 (8.72%) polymorphic sites consisting of 51 transitions, four transversions and one multiple mutational change. The overall haplotype and nucleotide diversity were 0.899 and 0.01569, respectively. Snail populations in Anhui had higher genetic diversity than in Jiangsu. 73.32% of total variation was distributed among sites and 26.68% within sites. Snails were significantly separated according to eco-epidemiological settings in both network and phylogenetic analyses. CONCLUSION: Our results could provide important guidance towards assessing coevolutionary interactions of snails with S. japonicum, as well as for future molluscan host monitoring and control activities.


Assuntos
Ciclo-Oxigenase 1/genética , Gastrópodes/classificação , Gastrópodes/genética , Genes Mitocondriais , Variação Genética , Animais , Genética Populacional , Haplótipos , Humanos , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
8.
Appl Opt ; 61(8): 2103-2107, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35297903

RESUMO

A novel, to the best of our knowledge, four-band tunable absorber sensor, based on a graphene layer, is presented. The proposed sensor configuration is composed of a single monolayer of graphene placed on top of a SiO2 dielectric substrate, whereas a gold grounding plane is placed beneath the SiO2. In addition, the resonant frequencies of the sensor can be directly controlled by adjusting the Fermi level of graphene, while the absorption rate reaches a value greater than 99% at all resonant peaks. The acquired calculation results of the refractive index sensitivity of our proposed sensor show that the four resonant peaks possess superior sensing characteristics. Additionally, by covering the measured objects with different refractive indices, the acquired results indicate that the sensing performance of the sensor exhibits good linearity. From our analysis, it is concluded that the absorbing sensor exhibits a broad range of potential applications in the biomedical field.

9.
Acta Pharmacol Sin ; 39(8): 1393-1404, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29417949

RESUMO

Cryptotanshinone (CT) is the main active component in the root of Salvia miltiorrhiza Bunge (SMB) that displays antibacterial, anti-inflammatory and anticancer activities. In this study, we characterized phase I and phase II metabolism of CT in human liver microsomes in vitro and identified the metabolic enzymes (CYPs and UGTs) involved. The metabolites of CT generated by CYPs were detected using LC-MS/MS and the CYP subtypes involved in the metabolic reactions were identified using chemical inhibitors of CYP enzymes and recombinant human CYP enzymes (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). Glucuronidation of CT was also examined, and the UGT subtypes involved in the metabolic reactions were identified using recombinant human UGT enzymes (1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15 and 2B17). After adding NADPH to the human liver microsomes incubation system, CT was transformed into 6 main dehydrogenation and hydroxylation metabolites. CYP2A6, CYP3A4 and CYP2C19 were the major contributors to the transformation of its hydroxylation metabolites. CYP2C19, CYP1A2 and CYP3A4 were the major contributors to the transformation of its hydrogenation metabolites in human liver microsomes. This study showed that the metabolites at m/z of 473 were mediated by UGT1A9 and that the metabolites at m/z of 489 were mediated by UGT2B7 and UGT2B4. CT was extensively metabolized by UGTs following metabolism by CYPs in the liver.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Glucuronosiltransferase/metabolismo , Fenantrenos/metabolismo , Inibidores das Enzimas do Citocromo P-450/farmacologia , Ensaios Enzimáticos , Glucuronídeos/biossíntese , Glucuronídeos/química , Humanos , Microssomos Hepáticos/metabolismo , Estrutura Molecular , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fenantrenos/química , Proteínas Recombinantes/metabolismo
10.
J Biol Chem ; 290(31): 19218-32, 2015 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-26082489

RESUMO

Endotoxin tolerance reprograms Toll-like receptor (TLR) 4-mediated macrophage responses by attenuating induction of proinflammatory cytokines while retaining expression of anti-inflammatory and antimicrobial mediators. We previously demonstrated deficient TLR4-induced activation of IL-1 receptor-associated kinase (IRAK) 4, IRAK1, and TANK-binding kinase (TBK) 1 as critical hallmarks of endotoxin tolerance, but mechanisms remain unclear. In this study, we examined the role of the E3 ubiquitin ligase Pellino-1 in endotoxin tolerance and TLR signaling. LPS stimulation increased Pellino-1 mRNA and protein expression in macrophages from mice injected with saline and in medium-pretreated human monocytes, THP-1, and MonoMac-6 cells, whereas endotoxin tolerization abrogated LPS inducibility of Pellino-1. Overexpression of Pellino-1 in 293/TLR2 and 293/TLR4/MD2 cells enhanced TLR2- and TLR4-induced nuclear factor κB (NF-κB) and expression of IL-8 mRNA, whereas Pellino-1 knockdown reduced these responses. Pellino-1 ablation in THP-1 cells impaired induction of myeloid differentiation primary response protein (MyD88), and Toll-IL-1R domain-containing adapter inducing IFN-ß (TRIF)-dependent cytokine genes in response to TLR4 and TLR2 agonists and heat-killed Escherichia coli and Staphylococcus aureus, whereas only weakly affecting phagocytosis of heat-killed bacteria. Co-expressed Pellino-1 potentiated NF-κB activation driven by transfected MyD88, TRIF, IRAK1, TBK1, TGF-ß-activated kinase (TAK) 1, and TNFR-associated factor 6, whereas not affecting p65-induced responses. Mechanistically, Pellino-1 increased LPS-driven K63-linked polyubiquitination of IRAK1, TBK1, TAK1, and phosphorylation of TBK1 and IFN regulatory factor 3. These results reveal a novel mechanism by which endotoxin tolerance re-programs TLR4 signaling via suppression of Pellino-1, a positive regulator of MyD88- and TRIF-dependent signaling that promotes K63-linked polyubiquitination of IRAK1, TBK1, and TAK1.


Assuntos
Proteínas Nucleares/fisiologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Ubiquitina-Proteína Ligases/fisiologia , Animais , Células HEK293 , Humanos , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase Quinases/metabolismo , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Monócitos/metabolismo , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/metabolismo , Ativação Transcricional/imunologia , Ubiquitinação
11.
Med Sci Monit ; 22: 1801-7, 2016 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-27234982

RESUMO

BACKGROUND Acinetobacter baumannii is an important nosocomial pathogen which shows a high level of mortality risk. Several papers have reported biofilm formation as a well-known pathogenic mechanism in A. baumannii infections and exceptional antibiotic resistance. The study aims to explore the potential relationships between biofilm-related genes and antimicrobial resistance. MATERIAL AND METHODS Samples from 122 patients with lower respiratory tract infections of A. baumannii were collected at Fujian Longyan First Hospital from January 2013 to September 2014. A. baumannii was isolated from sputum specimens. Biofilm-related genes including abaI, csuE, ompA, and bla-PER1 were analyzed by PCR. The minimum inhibitory concentration method was used to determine the sensitivity of each strain to antibiotics. RESULTS The clinical manifestations of A. baumannii-induced lower respiratory tract infections lacked specificity. Infected patients were most commonly admitted to intensive care units (54.9%) and frequently had chronic obstructive pulmonary disease (27.0%). The detection rates of abaI and csuE were both 59.8%, and those of ompA and bla-PER1 were 100% and 0%, respectively. After genetic testing, antimicrobial resistance to amikacin, ampicillin/sulbactam, and 14 other types of antimicrobials was higher in abaI- and csuE-positive strains than in abaI- and csuE-negative strains (P<0.05). CONCLUSIONS The findings of our study suggest that abaI- and csuE-positive Acinetobacter baumannii strains are associated with a higher incidence of antibiotic resistance in 14 types of antimicrobials.


Assuntos
Acinetobacter baumannii/genética , Acinetobacter baumannii/fisiologia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Idoso , China , Farmacorresistência Bacteriana Múltipla , Feminino , Genes Bacterianos/efeitos dos fármacos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Estudos Retrospectivos
12.
Int J Mol Sci ; 17(5)2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27153056

RESUMO

Transmembrane 4 superfamily member 1 (TM4SF1) is a member of tetraspanin family, which mediates signal transduction events regulating cell development, activation, growth and motility. Our previous studies showed that TM4SF1 is highly expressed in liver cancer. HepG2 cells were transfected with TM4SFl siRNA and TM4SF1-expressing plasmids and their biological functions were analyzed in vitro and in vivo. HepG2 cells overexpressing TM4SF1 showed reduced apoptosis and increased cell migration in vitro and enhanced tumor growth and metastasis in vivo, whereas siRNA-mediated silencing of TM4SF1 had the opposite effect. TM4SF1 exerts its effect by regulating a few apoptosis- and migration-related genes including caspase-3, caspase-9, MMP-2, MMP-9 and VEGF. These results indicate that TM4SF1 is associated with liver tumor growth and progression, suggesting that TM4SF1 may be a potential target for treatment of liver cancer in future.


Assuntos
Antígenos de Superfície/metabolismo , Proliferação de Células , Proteínas de Neoplasias/metabolismo , Antígenos de Superfície/genética , Apoptose , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Movimento Celular , Células Hep G2 , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Neoplasias/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Eur J Pharmacol ; 978: 176773, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936453

RESUMO

The interleukin-1 receptor-associated kinase (IRAK) family is a group of serine-threonine kinases that regulates various cellular processes via toll-like receptor (TLR)/interleukin-1 receptor (IL1R)-mediated signaling. The IRAK family comprises four members, including IRAK1, IRAK2, IRAK3, and IRAK4, which play an important role in the expression of various inflammatory genes, thereby contributing to the inflammatory response. IRAKs are key proteins in chronic and acute liver diseases, and recent evidence has implicated IRAK family proteins (IRAK1, IRAK3, and IRAK4) in the progression of liver-related disorders, including alcoholic liver disease, non-alcoholic steatohepatitis, hepatitis virus infection, acute liver failure, liver ischemia-reperfusion injury, and hepatocellular carcinoma. In this article, we provide a comprehensive review of the role of IRAK family proteins and their associated inflammatory signaling pathways in the pathogenesis of liver diseases. The purpose of this study is to explore whether IRAK family proteins can serve as the main target for the treatment of liver related diseases.

14.
Am J Chin Med ; 52(1): 1-33, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38351701

RESUMO

Obesity is a common metabolic syndrome that causes a significant burden on individuals and society. Conventional therapies include lifestyle interventions, bariatric surgery, and pharmacological therapies, which are not effective and have a high risk of adverse events. Acupuncture is an effective alternative for obesity, it modulates the hypothalamus, sympathetic activity and parasympathetic activity, obesity-related hormones (leptin, ghrelin, insulin, and CCK), the brain-gut axis, inflammatory status, adipose tissue browning, muscle blood flow, hypoxia, and reactive oxygen species (ROS) to influence metabolism, eating behavior, motivation, cognition, and the reward system. However, hypothalamic regulation by acupuncture should be further demonstrated in human studies using novel techniques, such as functional MRI (fMRI), positron emission tomography (PET), electroencephalogram (EEG), and magnetoencephalography (MEG). Moreover, a longer follow-up phase of clinical trials is required to detect the long-term effects of acupuncture. Also, future studies should investigate the optimal acupuncture therapeutic option for obesity. This review aims to consolidate the recent improvements in the mechanism of acupuncture for obesity as well as discuss the future research prospects and potential of acupuncture for obesity.


Assuntos
Terapia por Acupuntura , Obesidade , Humanos , Obesidade/etiologia , Terapia por Acupuntura/métodos , Tecido Adiposo , Imageamento por Ressonância Magnética/métodos
15.
Cancer Immunol Immunother ; 62(2): 237-44, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22868899

RESUMO

Although polyinosinic-polycytidylic acid (poly(I:C)) has been applied in tumor immunity as a Toll-like receptor 3 (TLR3) ligand, the interaction between poly(I:C) and TLR3 is still unclear, as are the mechanisms underlying the antitumor effect of poly(I:C). Our aim was to investigate the interaction between poly(I:C) and TLR3, as well as the mechanisms underlying the antitumor effect of poly(I:C). NK92 cells were maintained in medium (untreated group), or medium containing E7(44-62) (E7 group) or E7(44-62)+poly(I:C) (poly(I:C)/E7 group), and we measured the expression of TLR3 mRNA, p-p65, and IκB-α protein. The cells were first incubated in medium alone or medium containing TLR3 monoclonal antibody, and then in medium containing poly(I:C)/E7. Finally, we measured the level of interferon-beta (INF-ß) in the supernatant and determined the tumor cell-killing effect of the NK92 cells. At 1 h, the expression of TLR3 mRNA in the poly(I:C)/E7 group was markedly higher than that in the untreated and E7 groups (P < 0.05). When compared with the poly(I:C)/E7 group, the expression of IκB-α was dramatically increased in the E7 and untreated groups, and the expression of p-p65 was dramatically decreased in the E7 and untreated groups (all P < 0.05). At 24 h, INF-ß content and tumor cell-killing activity in the poly(I:C)/E7 group were markedly higher than those in the untreated group (P < 0.001, <0.05, respectively). Treatment with TLR3 monoclonal antibody significantly inhibited poly(I:C)/E7-induced INF-ß secretion and tumor cell-killing activity in NK92 cells (P < 0.001, <0.05, respectively). The interaction between poly(I:C) and TLR3 plays an important role in the antitumor immunity of NK92 cells. In addition, the interaction between poly(I:C) and TLR3 increases INF-ß expression, which may be attributed to the activation of NFκB.


Assuntos
Adjuvantes Imunológicos/farmacologia , Indutores de Interferon/farmacologia , Poli I-C/farmacologia , Receptor 3 Toll-Like/agonistas , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Carcinoma/imunologia , Linhagem Celular , Células Cultivadas , Feminino , Células HeLa , Humanos , Proteínas I-kappa B/biossíntese , Interferon beta/biossíntese , Interferon beta/imunologia , Interferon beta/metabolismo , Células Matadoras Naturais/imunologia , Ligantes , Inibidor de NF-kappaB alfa , Receptor 3 Toll-Like/antagonistas & inibidores , Receptor 3 Toll-Like/biossíntese , Neoplasias do Colo do Útero/imunologia
16.
Tumour Biol ; 34(3): 1615-23, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23430582

RESUMO

Previously, we demonstrated that treatment with E7(44-62) and the adjuvant polyinosinic-cytidylic acid (poly(I:C)) in a rodent model generates antitumor immune responses, but the effect of E7(44-62) with poly(I:C) on natural killer (NK)- and dendritic cell (DC)-mediated antitumor activities is still unclear. Our goal was to examine the antitumor effects of E7(44-62) with poly(I:C). We examined the ability of E7(44-62) with poly(I:C) to induce toll-like receptor 3 (TLR3) expression, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) mRNA expression, and tumor cell-killing activity in human NK cells as well as its ability to induce CD11c and CD86 expression and proliferation in human DCs. We found that E7(44-62) with poly(I:C) treatment markedly increased TLR3 expression and cytotoxicity against HeLa cells in human NK92 cells. Moreover, treatment with E7(44-62) and poly(I:C) markedly up-regulated IFN-γ and TNF-α mRNA expression in NK92 cells. Human patients with cervical cancer exhibited a marked decrease in the frequency of DCs; however, ex vivo treatment with E7(44-62) and poly(I:C) restored DC frequency. Stimulation of human DCs in patients with E7(44-62) and poly(I:C) led to high levels of CD11c and CD86 expression. Our data reveal the involvement of E7(44-62) combined with poly(I:C) in potentiating antitumor cytotoxicity and cytokine-producing activities in human NK92 cells and DCs.


Assuntos
Células Dendríticas/imunologia , Células Matadoras Naturais/imunologia , Poli I-C/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adjuvantes Imunológicos , Adulto , Estudos de Casos e Controles , Colo do Útero/metabolismo , Citocinas/metabolismo , Células Dendríticas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Células Matadoras Naturais/metabolismo , Pessoa de Meia-Idade , Receptor 3 Toll-Like/metabolismo , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/metabolismo , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/metabolismo
17.
Hepatogastroenterology ; 60(121): 1-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22773301

RESUMO

BACKGROUND/AIMS: The detection of hepatocellular carcinoma (HCC) cells in the peripheral blood is not only important for the diagnosis of FICC, but is also of critical importance for early detection of hematogenous metastasis of HCC. The purpose of this study was to measure Alpha-fetoprotein (AFP) mRNA in the peripheral blood and telomerase activity in peripheral blood monocytes to determine their utility, in isolation and concert, in the early diagnosis of HCC. METHODOLOGY: Nested RT-PCR was employed to detect the mRNA expression of AFP in the peripheral blood, and PCR-ELISA was used to measure the telomerase activity of peripheral blood mononuclear cells (PBMCs) in patients with HCC, benign hepatic tumors, chronic liver diseases and healthy subjects. RESULTS: Of the 30 HCC patients, 22 (73.3%) were positive for AFP, and 28/30 (93.3%) HCC patients were positive for telomerase activity. The mRNA expression of AFP was positively correlated with telomerase activity in HCC patients (r=0.6742, p<0.05). CONCLUSIONS: Detection of both mRNA expression of AFP in the peripheral blood and telomerase activity in PBMCs may prove to play an important role in achieving an early diagnosis of HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Monócitos/enzimologia , RNA Mensageiro/sangue , Telomerase/sangue , alfa-Fetoproteínas/genética , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , alfa-Fetoproteínas/análise
18.
Front Med (Lausanne) ; 10: 1130692, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37020678

RESUMO

Background: The benefits of anatomic resection (AR) vs. non-anatomic resection (NAR) in patients with primary intrahepatic cholangiocarcinoma (ICC) with hepatolithiasis (HICC) are unclear. This study aimed to compare the long-term outcomes of AR vs. NAR in patients with HICC. Methods: A total of 147 consecutive patients with HICC who underwent R0 hepatectomy were included. Overall survival (OS) and recurrence-free survival (RFS) following AR vs. NARs were compared using a 1:1 propensity score matching (PSM) analysis. A subgroup analysis was also conducted according to whether there are lymph node metastases (LNM). Results: In a multivariate analysis, CA 19-9 (>39 U/L), microvascular invasion, LNM, and NAR were independent risk factors for poor RFS and OS rates, whereas multiple tumors were independent risk factors for OS. AR had better 1-, 3-, and 5-year RFS and OS rates than NAR (OS: 78.7, 58.9, and 28.5%, respectively, vs. 61.2, 25.4, and 8.8%, respectively; RFS: 59.5, 36.5, and 20.5%, respectively, vs. 38.2, 12.1, and 6.9%, respectively). After PSM, 100 patients were enrolled. The NAR group also had significantly poorer OS and RFS (OS: 0.016; RFS: p = 0.010) than the AR group. The subgroup analysis demonstrated that in HICC without LNM, OS and RFS were significantly poorer in the NAR group than the AR group, while no significant differences were observed in HICC with LNM before or after PSM. Conclusion: Anatomic resection was associated with better long-term survival outcomes than NAR in patients with HICC, except for patients with LNM.

19.
Eur J Surg Oncol ; 49(4): 802-810, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36586787

RESUMO

BACKGROUND: The impact of sarcopenia on textbook outcome (TO) after hepatectomy in hepatocellular carcinoma (HCC) patients remains unclear. This study aimed to investigate the association between sarcopenia and TO, to clarify its long and short-term prognostic value, and to develop a nomogram model based on sarcopenia and TO for survival prediction. METHODS: Patients who underwent HCC resection between January 2012 and March 2017 in three large hospitals in Fujian were retrospectively recruited and divided into sarcopenia and non-sarcopenia groups based on skeletal muscle index (SMI) values. TO was defined as no 30-day morality, no 30-day readmission, negative margins, no prolonged hospital stay, and no major complications. Multivariate regression was used to screen for clinical factors associated with TO. Nomograms of overall survival (OS) and recurrence-free survival (RFS) after hepatectomy for HCC were developed. RESULTS: A total of 1172 patients were included in the study. The TO rates were 28.74% (121/421 patients) in the sarcopenia group and 43.4% (326/751 patients) in the non-sarcopenia group. The results showed that sarcopenia was an independent predictor of TO (p < 0.001), TO was an independent predictor of perioperative treatment-related sarcopenia (PTRS)(p = 0.002), and TO was an independent predictor of OS and RFS (p < 0.001). Nomogram models based on sarcopenia and TO were generated and accurately predicted OS and RFS at 1, 3, and 5 years. CONCLUSION: Both sarcopenia and TO are independent predictors of OS and RFS after HCC resection. Sarcopenia was an independent predictor of TO. Sarcopenia influenced long-term survival by affecting short-term postoperative outcomes.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Sarcopenia , Humanos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Prognóstico , Nomogramas , Sarcopenia/complicações , Sarcopenia/epidemiologia , Hepatectomia/métodos
20.
Liver Cancer ; 12(3): 229-237, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37767067

RESUMO

Introduction: The actual rate of conversion surgery and its prognostic advantages remain unclear. This study aimed to assess the outcomes of salvage surgery after conversion therapy with triple therapy (transcatheter arterial chemoembolization [TACE] combined with lenvatinib plus anti-PD-1 antibodies) in patients with initially unresectable hepatocellular carcinoma (uHCC). Methods: Patients with initially uHCC who received at least one cycle of first-line triple therapy and salvage surgery at five major cancer centers in China were included. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) rates after salvage surgery. The secondary endpoints were perioperative complications, 90-day mortality, and pathological tumor response. Results: Between June 2018 and December 2021, 70 patients diagnosed with uHCC who underwent triple therapy and salvage surgery were analyzed: 39 with Barcelona Clinic Liver Cancer (BCLC) stage C, 22 with BCLC stage B, and 9 with BCLC stage A disease. The median interval between the start of triple therapy and salvage surgery was 4.3 months (range, 1.7-14.2 months). Pathological complete response and major pathological response were observed in 29 (41.4%) and 59 (84.3%) patients, respectively. There were 2 cases of perioperative mortality (4.3%) and 5 cases of severe perioperative complications (7.1%). With a median follow-up of 12.9 months after surgery (range, 0.3-36.8 months), the median OS and RFS were not reached. The 1- and 2-year OS rates were 97.1% and 94.4%, respectively, and the corresponding RFS rates were 68.9% and 54.4%, respectively. Conclusion: First-line combination of TACE, lenvatinib, and anti-PD-1 antibodies provides a better chance of conversion therapy in patients with initially uHCC. Furthermore, salvage surgery after conversion therapy is effective and safe and has the potential to provide excellent long-term survival benefits.

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