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Photodynamic therapy (PDT) is nowadays widely employed in cancer treatment. We sought to assess the efficacy of combining PDT with anti-programmed cell death protein 1 (PD1) and to investigate the associated mechanisms in nonsmall cell lung cancer (NSCLC). We established a xenograft tumor model in C57BL/6J mice using Lewis lung carcinoma (LLC) cells, recorded tumor growth, and quantified reactive oxygen species (ROS) levels using a ROS detection kit. Pathological changes were assessed through H&E staining, while immunofluorescence (IF) was used to determine the expression of CD8 and Foxp3. Transcriptomic analysis was conducted, analyzing differential expressed genes (DEGs) among control, PDT, and PDT combined with anti-PD1 (PDT+anti-PD1) groups. Functional enrichment analysis via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed. The Cancer Genome Atlas (TCGA) database was utilized to analyze the expression of aminolevulinate synthase gene (ALAS2), integrin alpha10 (ITGA10), ATP1A2, a disintegrin and metalloprotease 12 (ADAM12), and Lox1 in lung adenocarcinoma and adjacent tissues, with concurrent immune infiltration analysis. Quantitative real-time polymerase chain reaction and western blot were employed to measure mRNA and protein expression levels. Treatment with PDT combined with anti-PD1 significantly inhibited tumor growth and increased the number of CD8+ cells while decreasing Foxp3+ cells. Immune infiltration results presented ALAS2, ADAM12, and ITGA10 were associated with various types of T cells or macrophages. Additionally, the expression levels of EGFR, ERK, and PI3K/Akt were suppressed after PDT with anti-PD1 treatment. Our findings collectively suggest that PDT combined with anti-PD1 treatment could enhance the infiltration of CD8+ T cells, suppressing tumor growth, and this effect was associated with ALAS2, ITGA10, and ADAM12. The underlying mechanism might be linked to EGFR, ERK, and PI3K/Akt signaling. Overall, this study provides valuable insights into the application of PDT combined with anti-PD1 treatment in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linfócitos T CD8-Positivos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio , Neoplasias Pulmonares/tratamento farmacológico , Receptores ErbB , Fatores de Transcrição Forkhead , Imunidade , 5-Aminolevulinato SintetaseRESUMO
OBJECTIVE: To evaluate the diagnostic values of serum platelet count (PC), mean platelet volume ratio (MPV), platelet count to mean platelet volume ratio (PVR), platelet to lymphocyte ratio (PLR), platelet to neutrophil ratio (PNR), PC/Albumin-globulin ratio (PC/AGR), and PC/C-reactive protein (PC/ CRP) in the diagnosis of periprosthetic joint infection (PJI). METHODS: The medical records were retrospectively analyzed of the 158 patients who had undergone hip or knee revisions from January 2018 to May 2022. Of them, 79 cases were diagnosed with PJI and 79 with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of CRP, the erythrocyte sedimentation rate (ESR), PC, MPV, PVR, PLR, PNR, PC/AGR, and PC/CRP in the 2 groups were recorded and analyzed. In addition, tests were performed according to different joint types. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator. The diagnostic value for each indicator was calculated according to the area under the curve (AUC). RESULTS: The PC, PVR, PLR and PC/AGR levels in the PJI group were significantly higher than those in the AL group, while PC/CRP levels were significantly lower (P < 0.001). The AUC for PC/CRP, and PC/AGR was 0.804 and 0.802, respectively, which were slightly lower than that of CRP (0.826) and ESR (0.846). ROC analysis for PC/CRP, and PC/AGR revealed a cut-off value of 37.80 and 160.63, respectively, which provided a sensitivity of 73.42% and 84.81% and a specificity of 75.95% and 65.82% for PJI. The area under the curve of PLR and PC was 0.738 and 0.702. The area under the curve values for PVR, PNR, and MPV were 0.672, 0.553, and 0.544, respectively. CONCLUSIONS: The results of this study suggest that PC, PLR, PC/CRP, and PC/AGR values do not offer significant advantages over ESR or CRP values when employed for the diagnosis of PJI. PVR, PNR, and MPV were not reliable in the diagnosis of PJI.
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Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Humanos , Biomarcadores , Estudos Retrospectivos , Infecções Relacionadas à Prótese/cirurgia , Artroplastia de Quadril/efeitos adversos , Proteína C-Reativa/análise , Sensibilidade e Especificidade , Artrite Infecciosa/cirurgia , Sedimentação SanguíneaRESUMO
BACKGROUND: Prosthesis removal and antibiotic bone cement spacer implantation is a very important link in two-stage revision of periprosthetic joint infection (PJI) after artificial joint replacement, which is key to the smooth progress of second-stage revision surgery. There are few reports on the risk factors of reinfection after prosthesis removal and antibiotic bone cement spacer implantation for PJI. This study aimed to investigate the risk factors of reinfection after prosthesis removal and antibiotic bone cement spacer implantation for the treatment of PJI. METHODS: Clinical data of 40 patients who underwent prosthesis removal and antibiotic bone cement spacer implantation for PJI after arthroplasty in our hospital from January 2013 to July 2019 were retrospectively analyzed. During the follow-up period of at least 2 years, 21 patients underwent complete two-stage revision after the removal of the antibiotic bone cement spacer, and 19 patients did not receive a new prosthesis due to other factors, such as reinfection or the patient's wishes, record the infection control of patients during the treatment. Reinfection after prosthesis removal and antibiotic bone cement spacer implantation was defined as failure of effective control of infection, symptoms of reinfection, requires increased antibiotic therapy or reoperation. Multivariate Cox proportional hazards model was used to analyze the risk factors associated with reinfection after prosthesis removal and antibiotic bone cement spacer implantation. RESULTS: Of the 40 patients, nine (22.5%) developed reinfection after prosthesis removal and antibiotic bone cement spacer implantation with a mean follow-up duration of 31 months, and multivariate analysis revealed that history of prior revision surgery (hazard ratio [HR] = 6.317, confidence interval [CI]: 1.495-26.700; p = 0.012) and presence of sinus tract before treatment (HR = 5.117, 95% CI: 1.199-21.828; p = 0.027) were independent risk factors for reinfection after prosthesis removal and antibiotic bone cement spacer implantation. CONCLUSION: History of prior revision surgery and presence of sinus tract are two independent risk factors for reinfection in patients with PJI treated with prosthesis removal and antibiotic bone cement spacer implantation.
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Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Humanos , Cimentos Ósseos/efeitos adversos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Reinfecção , Reoperação/efeitos adversos , Artrite Infecciosa/tratamento farmacológico , Artroplastia de Quadril/efeitos adversos , Próteses e Implantes/efeitos adversos , Fatores de Risco , Resultado do TratamentoRESUMO
Lymph nodes are distributed all over the body and are part of the lymphatic system. The interferon-stimulated gene 15 kDa protein (ISG15) and prostaglandins (PGs) are involved in the establishment of pregnancy and are expressed in the uterus during early pregnancy in sheep. In this study, the ovine lymph nodes were obtained on Day 16 of the estrous cycle, and Days 13, 16, and 25 of pregnancy, and the expression of ISG15 and PG synthases, including cyclooxygenase 1 (COX-1), COX-2, prostaglandin E (PGE) synthase (PTGES), and a PGF synthase (aldo-keto reductase family 1, member B1, AKR1B1) were detected by quantitative real-time polymerase chain reaction, western blot analysis, and immunohistochemistry analysis. Our results showed that there were peaks in the expression of mRNAs and the proteins of ISG15, COX-1, COX-2, PTGES, and AKR1B1 in the lymph nodes during early pregnancy and that the COX-2 and AKR1B1 proteins were limited to the subcapsular sinus and lymph sinuses. In conclusion, the ISG15, COX-1, COX-2, PTGES, and AKR1B1 were upregulated in the maternal lymph nodes, which may be beneficial for the development of conceptus, maternal systemic immunoregulation, and anti-luteolysis during early pregnancy in sheep.
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Citocinas/biossíntese , Regulação da Expressão Gênica/fisiologia , Linfonodos/metabolismo , Gravidez/metabolismo , Prostaglandina-Endoperóxido Sintases/biossíntese , Ovinos/metabolismo , Animais , FemininoRESUMO
The complement system can be activated spontaneously for immune surveillance or induced to clear invading pathogens, in which the membrane attack complex (MAC, C5b-9) plays a critical role. CD59 is the sole membrane complement regulatory protein (mCRP) that restricts MAC assembly. CD59, therefore, protects innocent host cells from attacks by the complement system, and host cells require the constitutive and inducible expression of CD59 to protect themselves from deleterious destruction by complement. However, the mechanisms that underlie CD59 regulation remain largely unknown. In this study we demonstrate that the widely expressed transcription factor Sp1 may regulate the constitutive expression of CD59, whereas CREB-binding protein (CBP)/p300 bridge NF-κB and CREB, which surprisingly functions as an enhancer-binding protein to induce the up-regulation of CD59 during in lipopolysaccharide (LPS)-triggered complement activation, thus conferring host defense against further MAC-mediated destruction. Moreover, individual treatment with LPS, TNF-α, and the complement activation products (sublytic MAC (SC5b-9) and C5a) could increase the expression of CD59 mainly by activating NF-κB and CREB signaling pathways. Together, our findings identify a novel gene regulation mechanism involving CBP/p300, NF-κB, and CREB; this mechanism suggests potential drug targets for controlling various complement-related human diseases.
Assuntos
Antígenos CD59/metabolismo , Proteína de Ligação a CREB/metabolismo , Ativação do Complemento/fisiologia , Proteínas do Sistema Complemento/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteína p300 Associada a E1A/metabolismo , NF-kappa B/metabolismo , Antígenos CD59/genética , Proteína de Ligação a CREB/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína p300 Associada a E1A/genética , Elementos Facilitadores Genéticos/fisiologia , Células HeLa , Humanos , Lipopolissacarídeos/farmacologia , Transdução de Sinais/fisiologia , Fator de Transcrição Sp1/metabolismo , Transcrição Gênica/fisiologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Células U937RESUMO
Topological insulators have been theoretically predicted as promising candidates for broadband photonics devices due to its large bulk band gap states in association with the spin-momentum-locked mass-less Dirac edge/surface states. Unlike the bulk counterpart, few-layer topological insulators possess some intrinsic optical advantages, such as low optical loss, low saturation intensity and high concentration of surface state. Herein, we use a solvothermal method to prepare few-layer Bi2Te3 flakes. By sandwiching few-layer Bi2Te3 flakes with polymethyl methacrylate (PMMA) polymer, a novel light modulation device had been successfully fabricated with high chemical and thermal stabilities as well as excellent mechanical durability, originating from the contribution of PMMA acting as buffer layers that counteract excessive mechanical bending within the fragile Bi2Te3 flakes. The incorporation of the as-fabricated PMMA-TI-PMMA as saturable absorber, which could bear long-term mechanical loadings, into the fiber laser cavity generated the stable dissipative soliton mode-locking with a 3-dB spectral bandwidth up to 51.62 nm and tunable wavelength range of 22 nm. Our work provides a new way of fabricating PMMA-TI-PMMA sandwiched composite structure as saturable absorber with promising applications for laser operation.
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Conventional circularly polarized light (CPL) detectors necessitate several optical elements, posing difficulties in achieving miniature and integrated devices. Recently developed organic CPL detectors require no additional optical elements but usually suffer from low detectivity or low asymmetry factor (g-factor). Here, an organic CPL detector with excellent detectivity and a high g-factor is fabricated. By employing an inverted quasi-planar heterojunction (IPHJ) structure and incorporating an additional liquid crystal film, a CPL detector with an outstanding g-factor of 1.62 is developed. Unfavorable charge injection is effectively suppressed by the IPHJ structure, which reduces the dark current of the organic photodetector. Consequently, a left CPL detectivity of 6.16 × 1014 Jones at 640 nm is realized, surpassing all of the latest photodiode-type CPL detectors. Adopting a liquid crystal film with adjustable wavelengths of selectively reflected light, the hybrid device achieves narrow dual-band CPL detection, varying from 530 to 640 nm, with a half-maximum full width below 90 nm. Notably, the device achieves excellent stability of 260 000 on/off cycles without attenuation. To the best of the authors' knowledge, all these features have rarely been reported in previous work. The CPL detector arrays are also demonstrated for encrypted communications and color imaging.
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We proposed a scheme to manipulate the Goos-Hänchen shift of a light beam reflected from the depletion-type device via external voltage bias. It is shown that the lateral shift of the reflected probe beam can be easily controlled by adjusting the reverse voltage bias and the incidence angle. Using this scheme, the lateral shift can be tuned from negative to positive, without changing the original structure of the depletion-type device. Numerical calculations further indicate that the influence of structure parameters and light wavelength can be reduced via readjustment of the reverse bias. The proposed structure has the potential application for the integrated electronic devices.
Assuntos
Eletrônica/instrumentação , Lentes , Metais/química , Modelos Teóricos , Refratometria/instrumentação , Semicondutores , Ressonância de Plasmônio de Superfície/instrumentação , Simulação por Computador , Desenho Assistido por Computador , Condutividade Elétrica , Campos Eletromagnéticos , Desenho de Equipamento , Análise de Falha de EquipamentoRESUMO
OBJECTIVE: Significant progress has been made in recent years in the diagnosis of periprosthetic joint infections (PJI). However, the lack of a gold standard test for the diagnosis of PJI remains a challenge.The aim of this study was to evaluate the diagnostic values of the albumin/fibrinogen ratio (AFR), the C-reactive protein/albumin ratio (CAR), and the levels of fibrinogen (FIB) and albumin (ALB) in the diagnosis of PJI. METHODS: The medical records of 158 patients who had undergone hip or knee revisions from January 2018 to May 2022 were retrospectively analyzed. Of these patients, 79 were diagnosed with PJI, while 79 were diagnosed with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of C-reactive protein (CRP), ALB, and FIB; the erythrocyte sedimentation rate (ESR); and the AFR and CAR in the two groups were recorded and analyzed. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator; the diagnostic value for each indicator was calculated as the area under the curve (AUC). RESULTS: The ESR, CRP, FIB, and CAR values in the PJI group were significantly higher than those in the AL group, and the ALB and AFR values were significantly lower than those in the AL group (p < 0.001). The AUC values of AFR and fibrinogen were 0.851 and 0.848, respectively, which were slightly higher than those of CRP (0.826) and ESR (0.846). The AUC of CAR was 0.831 which was slightly lower than that of CRP (0.846). ALB had an AUC of 0.727. The optimal threshold, sensitivity, and specificity, respectively, were 10.05, 84.81%, and 82.28% for AFR; 4.03 µg/mL, 77.22%, and 86.08% for FIB; 0.23, 72.15%, and 82.28% for CAR; and 37.30 g/L, 65.82%, and 73.42% for ALB. CONCLUSIONS: AFR, CAR, and FIB are good new auxiliary diagnostic indicators of PJI, while ALB is of fair value for the diagnosis of PJI.
Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Hemostáticos , Infecções Relacionadas à Prótese , Humanos , Proteína C-Reativa/análise , Estudos Retrospectivos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/cirurgia , Biomarcadores , Artrite Infecciosa/cirurgia , Fibrinogênio/metabolismo , Sensibilidade e EspecificidadeRESUMO
Supramolecular chiral organization gives π-conjugated molecules access to fascinating specific interactions with circularly polarized light (CPL). Such a feature enables the fabrication of high-performance chiral organic electronic devices that detect or emit CPL directly. Herein, it is shown that chiral fused-ring electron-acceptor BTP-4F single-crystal-based phototransistors demonstrate distinguished CPL discrimination capability with current dissymmetry factor exceeding 1.4, one of the highest values among state-of-the-art direct CPL detectors. Theoretical calculations prove that the chirality at the supramolecular level in these enantiomeric single crystals originates from chiral exciton coupling of a unique quasi-2D supramolecular organization consisting of interlaced molecules with opposite helical conformation. Impressively, such supramolecular organization produces a higher dissymmetry factor along the preferred growth direction of the chiral single crystals in comparison to that of the short axis direction. Furthermore, the amplified, inverted, and also anisotropic current dissymmetry compared to optical dissymmetry is studied by finite element simulations. Therefore, a unique chiral supramolecular organization that is responsible for the excellent chiroptical response and anisotropic electronic properties is developed, which not only enables the construction of high-performance CPL detection devices but also allows a better understanding of the structure-property relationships in chiral organic optoelectronics.
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A 38-year-old male patient was diagnosed as acute non-ST-segment elevation myocardial infarction on Apr 21st 2021 and he received percutaneous transluminal coronary angioplasty for RCA via transradial artery access. He sought for second percutaneous coronary intervention in our center for frequently exertional angina on Sep 13th 2021. Proximal right radial artery pulsation can not be touched in physical examination, indicating right radial artery occlusion (RAO). Distal transradial access was applied and RAO was confirmed via angiography. With balloon pre-dilation, the guidewire and guiding catheter crossed the occlusion and coronary intervention was successfully completed. A Reewarm 2.5 × 220 mm paclitaxel drug-coated balloon (Endovastec, China) was released at 12 atm in radial arterial lesion with 90 s. Pulsation of radial artery can be well palpated 24 h after PCI. No oral anticoagulant was added. The right radial artery remained patent after 8-month and 14-month follow-up and there was no abnormal sensation or obstacle of right hand.
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We present a theoretical investigation of dispersive wave (DW) generation in nonlinear metamaterials (MMs). The role of the anomalous self-steepening (SS) effect, which can be either positive or negative, and the negative SS parameter can have a very large value compared to an ordinary positive-index material, in DW generation is particularly identified. It is demonstrated that the SS effect exerts a great impact on the peak power while has little effect on the frequency shift of DW. For positive third-order dispersion (TOD), the negative SS broadens the pulse spectrum and weakens the DW's peak power significantly, opposite to the case of positive SS. For negative TOD, however, the negative SS narrows the pulse spectrum and enhances the DW's peak power, also opposite to the case of positive SS. The results suggest that the DW generation in nonlinear MMs can be manipulated by SS effect to a large extent.
Assuntos
Tecnologia de Fibra Óptica/instrumentação , Iluminação/instrumentação , Modelos Teóricos , Desenho Assistido por Computador , Desenho de Equipamento , HumanosRESUMO
Pressure, as an independent thermodynamic parameter, is an effective tool to obtain novel material system and exotic physical phenomena not accessible at ambient conditions, because it profoundly modifies the charge, orbital and spin state by reducing the interatomic distance in crystal structure. However, the studies of magnetoelectricity and multiferroicity are rarely extended to high pressure dimension due to properties measured inside the high pressure vessel being a challenge. Here we reported the temperature-magnetic field-pressure magnetoelectric (ME) phase diagram of Y type hexaferrite Ba0.4Sr1.6Mg2Fe12O22derived from static pyroelectric current measurement and dynamic magnetodielectric in diamond anvil cell and piston cylinder cell. We found that a new spin-driven ferroelectric phase emerged atP= 0.7 GPa and sequentially ME effect disappeared aroundP= 4.3 GPa. The external pressure may enhance easy plane anisotropy to destabilize the longitudinal conical magnetic structure with the suppression of ME coefficient. These results offer essential clues for the correlation between ME effect and magnetic structure evolution under high pressure.
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Melatonin treatment can improve quality and in vitro development of porcine oocytes, but the mechanism of improving quality and developmental competence is not fully understood. In this study, porcine cumulus-oocyte complexes were cultured in TCM199 medium with non-treated (control), 10-5 M luzindole (melatonin receptor antagonist), 10-5 M melatonin, and melatonin + luzindole during in vitro maturation, and parthenogenetically activated (PA) embryos were treated with nothing (control), or 10-5 M melatonin. Cumulus oophorus expansion, oocyte survival rate, first polar body extrusion rate, mitochondrial distribution, and intracellular levels of reactive oxygen species (ROS) and glutathione of oocytes, and cleavage rate and blastocyst rate of the PA embryos were assessed. In addition, expression of growth differentiation factor 9 (GDF9), tumor protein p53 (P53), BCL2 associated X protein (BAX), catalase (CAT), and bone morphogenetic protein 15 (BMP15) were analyzed by real-time quantitative PCR. The results revealed that melatonin treatment not only improved the first polar body extrusion rate and cumulus expansion of oocytes via melatonin receptors, but also enhanced the rates of cleavage and blastocyst formation of PA embryos. Additionally, melatonin treatment significantly increased intraooplasmic level of glutathione independently of melatonin receptors. Furthermore, melatonin supplementation not only significantly enhanced mitochondrial distribution and relative abundances of BMP15 and CAT mRNA, but also decreased intracellular level of ROS and relative abundances of P53 and BAX mRNA of the oocytes. In conclusion, melatonin enhanced the quality and in vitro development of porcine oocytes, which may be related to antioxidant and anti-apoptotic mechanisms.
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Numerous factors have been claimed to play important roles in colorectal cancer (CRC) tumorigenesis, including myeloid-derived suppressor cells (MDSCs) and other immune cells, cytokines, and chemokines; however, the precise mechanisms of colorectal tumorigenesis remain elusive, and there is a lack of effective preventive treatments. Here, we investigated the role of complement system, a key regulator of immune surveillance and homeostasis, in colorectal tumorigenesis. Methods: The prototypical CRC model was induced by combined administration of azoxymethane (AOM)/ dextran sulfate sodium (DSS) in Wild-type (WT), C3-, C5-, C5ar1-, and C5ar2-deficient mice. Using flow cytometry, immunohistochemical staining and multiplex bead assay, we profiled the immune cells, cytokines and chemokines. Bone marrow transplantation was employed to determine the contribution of immune cells in colorectal tumorigenesis. Further, we used C5aR1 antagonist PMX205 to investigate the protective role in colorectal tumorigenesis. Results: Complement was extensively activated in inflamed tissues of AOM/DSS-induced murine CRC model, leading to multifaceted consequences. The deficiency of complement C5 or especially C5ar1, but not C3 almost completely prevented CRC tumorigenesis. C5a/C5aR1 signaling recruited MDSCs into the inflamed colorectum to impair CD8+ T cells, and modulated the production of critical cytokines and chemokines, thus initiating CRC. Moreover, the C5aR1 antagonist PMX205 strongly impeded colorectal tumorigenesis. Bone marrow transplantation further revealed that C5aR1 expression by immune cells was critical for colorectal tumorigenesis. Conclusion: Our study identifies C5a/C5aR1 signaling as a vital immunomodulatory program in CRC tumorigenesis and suggests a feasible preventive strategy.
Assuntos
Azoximetano/efeitos adversos , Linfócitos T CD8-Positivos/metabolismo , Colite/complicações , Neoplasias Colorretais/imunologia , Sulfato de Dextrana/efeitos adversos , Receptor da Anafilatoxina C5a/genética , Animais , Transplante de Medula Óssea , Colite/induzido quimicamente , Colite/genética , Colite/imunologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Complemento C3/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Masculino , Camundongos , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/farmacologiaRESUMO
Thymus is a primary lymphoid organ, must adapt to the presence of fetal alloantigens. Prostaglandins (PGs) have diverse effects to activate or inhibit the immune response, but effects of early pregnancy on the expression of PG synthases in ovine maternal thymus are unclear. In this study, ovine thymic samples were obtained at day 16 of the estrous cycle, and days 13, 16 and 25 of pregnancy. The expression of PG synthases, including cyclooxygenase 1 (COX-1), COX-2, PGE2 synthase (PTGES), and a prostaglandin F2α synthase (Aldo-keto reductase family 1, member B1, AKR1B1), was evaluated using quantitative real-time PCR, Western blot and immunohistochemistry analysis. In addition, the thymus/body ratio was also calculated. Our results showed that the expression of COX-2 mRNA and protein, AKR1B1 mRNA and dimer were up-regulated on day 25 of pregnancy (Pâ¯<â¯0.05), and expression of COX-1, PTGES mRNA and protein, AKR1B1 monomer and thymus/body ratio were similar at different stages of pregnancy and the estrous cycle. The immunohistochemistry results showed that the COX-2 and AKR1B1 proteins were located in the stromal cells, capillaries and thymic corpuscles. This is the first study to report that expression of COX-2 and AKR1B1 dimer is up-regulated in the maternal thymus during early pregnancy, suggesting that early pregnancy exerts its effects on maternal thymus, which is involved in immunomodulation during early pregnancy in sheep.
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Regulação Enzimológica da Expressão Gênica/fisiologia , Prenhez , Prostaglandina-Endoperóxido Sintases/metabolismo , Ovinos/fisiologia , Timo/metabolismo , Animais , Peso Corporal , Feminino , Tamanho do Órgão , Gravidez , Prenhez/fisiologia , Prostaglandina-Endoperóxido Sintases/genética , Timo/anatomia & histologia , Regulação para Cima/fisiologiaRESUMO
Interferon-tau (IFNT) is the main signal for the maternal recognition of pregnancy in ruminants, and exerts its effects by stimulating the expression of interferon-stimulated genes, including the expression of interferon-stimulated gene15â¯kDa protein (ISG15). Progesterone (P4) exerts significant immune effects on the uterus during early pregnancy in ruminants that are partly mediated by progesterone-induced blocking factor (PIBF). The thymus is necessary for the normal development of immunologic function. In this study, thymuses were obtained on day 16 of the estrous cycle and on days 13, 16 and 25 of pregnancy (nâ¯=â¯6 for each group) from ewes. Our results showed that the expression of ISG15, P4 receptor (PGR) and PIBF mRNA and the expression of ISG15 and ISG15-conjugated proteins were upregulated in the thymuses during early pregnancy, and the 89-kDa PGR isoform and the 80-kDa PIBF variant were expressed constantly in the thymuses. However, there was no expression of the 60-kDa PGR isoform and the 62-kDa PIBF variant on day 16 of the estrous cycle. ISG15 and ISG15-conjugated proteins were limited to the epithelial reticular cells, capillaries and thymic corpuscles. This paper reports for the first time that early pregnancy exerts its effects on the thymus through IFNT and P4 in sheep.
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Citocinas/metabolismo , Proteínas da Gravidez/metabolismo , Prenhez/genética , Receptores de Progesterona/metabolismo , Ovinos/fisiologia , Fatores Supressores Imunológicos/metabolismo , Animais , Citocinas/genética , Feminino , Regulação da Expressão Gênica , Gravidez , Proteínas da Gravidez/genética , Receptores de Progesterona/genética , Ovinos/metabolismo , Fatores Supressores Imunológicos/genéticaRESUMO
Two-dimensional Bi2Se3 nanosheets with hexagonal shape are synthesized by a solution synthetic route. The Bi2Se3 nanosheets are 120 nm in edge width and 7 nm in thickness. The size of the Bi2Se3 nanosheets can be controlled by choosing different kinds of reducing agents including hydroxylamine and ethylenediamine. Subsequently, we demonstrate a configuration of two-color all-optical switching based on plasma channels effect using the as-synthesized Bi2Se3 nanosheets as an optical media. The signal light can be modulated as two states including dot and ring shape by changing the intensity of control light. The modulated signal light exhibits excellent spatial propagation properties. As a type of interesting optical material, ultrathin two-dimensional Bi2Se3 nanosheets might provide an effective option for photoelectric applications.
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Ankylosing spondylitis (AS) is a chronic axial spondyloarthritis (SpA) resulting in back pain and progressive spinal ankyloses. Currently, there are no effective therapeutics targeting AS largely due to elusive pathogenesis mechanisms, even as potential candidates such as HLA-B27 autoantigen have been identified. Herein, we employed a proteoglycan (PG)-induced AS mouse model together with clinical specimens, and found that the complement system was substantially activated in the spinal bone marrow, accompanied by a remarkable proportion alteration of neutrophils and macrophage in bone marrow and spleen, and by the significant increase of TGF-ß1 in serum. The combined treatment with a bacteria-derived complement inhibitor Efb-C (C-terminal of extracellular fibrinogen-binding protein of Staphylococcus aureus) remarkably retarded the progression of mouse AS by reducing osteoblast differentiation. Furthermore, we demonstrated that two important modulators involved in AS disease, TGF-ß1 and RANKL, were elevated upon in vitro complement attack in osteoblast and/or osteoclast cells. These findings further unravel that complement activation is closely related with the pathogenesis of AS, and suggest that complement inhibition may hold great potential for AS therapy.
Assuntos
Anti-Inflamatórios/farmacologia , Dor nas Costas/tratamento farmacológico , Proteínas de Bactérias/farmacologia , Proteínas do Sistema Complemento/genética , Espondilite Anquilosante/tratamento farmacológico , Animais , Dor nas Costas/induzido quimicamente , Dor nas Costas/imunologia , Dor nas Costas/patologia , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Medula Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Proteínas do Sistema Complemento/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/patologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/imunologia , Osteoblastos/patologia , Cultura Primária de Células , Proteoglicanas/administração & dosagem , Ligante RANK/genética , Ligante RANK/imunologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Espondilite Anquilosante/induzido quimicamente , Espondilite Anquilosante/imunologia , Espondilite Anquilosante/patologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/imunologiaRESUMO
The fifth component of complement (C5) is considered to be the center of complement activation and function. However, there are no genetically engineered knockout mice for this gene, and the only commercially available inherited C5-deficient mice, in which a "TA" nucleotide deletion in the coding frame was previously identified, are in theC57BL/10Sn genetic background rather than the commonly used backgrounds C57BL/6 and BALB/c. Therefore, these mice must be backcrossed into the desired genetic background. Here, we developed an ARMS (amplification refractory mutation system) PCR method using a specific primer pair that was able to discriminate between the genotypes when the resulting product was analyzed by agarose gel electrophoresis. These results were supported by quantitative RT-PCR and semi-quantitative PCR and were consistent with the results from sequencing each backcrossed generation. Using ARMS-PCR method, we generated C5-deficient mice in the C57BL/6 background over 9 backcrossed generations and further verified the phenotype using complement-mediated hemolytic assays. In this study, we describe a simple, rapid and reliable PCR-based method for genotyping inherited C5-deficient mice that may be used to backcross C57BL/10Sn mice into other genetic backgrounds.