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BACKGROUND: Owing to the widespread use of chemical pesticides to control agricultural pests, pesticide tolerance has become a serious problem. In recent years, it has been found that symbiotic bacteria are related to pesticides tolerance. To investigate the potential role of microorganisms in the pesticide tolerance of Chilo suppressalis, this study was conducted. RESULTS: The insect was fed with tetracycline and cefixime as the treatment group (TET and CFM, respectively), and did not add antibiotics in the control groups (CK). The 16S rDNA sequencing results showed that antibiotics reduced the diversity of C. suppressalis symbiotic microorganisms but did not affect their growth and development. In bioassays of the three C. suppressalis groups (TET, CFM, and CK), a 72 h LC50 fitting curve was calculated to determine whether long-term antibiotic feeding leads to a decrease in pesticide resistance. The CK group of C. suppressalis was used to determine the direct effect of antibiotics on pesticide tolerance using a mixture of antibiotics and pesticides. Indirect evidence suggests that antibiotics themselves did not affect the pesticide tolerance of C. suppressalis. The results confirmed that feeding C. suppressalis cefixime led to a decrease in the expression of potential tolerance genes to chlorantraniliprole. CONCLUSIONS: This study reveals the impact of antibiotic induced changes in symbiotic microorganisms on the pesticide tolerance of C. suppressalis, laying the foundation for studying the interaction between C. suppressalis and microorganisms, and also providing new ideas for the prevention and control of C. suppressalis and the creation of new pesticides.
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Antibacterianos , Bactérias , Antibacterianos/farmacologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Praguicidas/farmacologia , Mariposas/microbiologia , Mariposas/efeitos dos fármacos , Simbiose , RNA Ribossômico 16S/genética , Microbiota/efeitos dos fármacos , Tetraciclina/farmacologiaRESUMO
BACKGROUND: Gout is one of the common inflammatory arthritis which affects many people for inflicting unbearable pain. Macrophage-mediated inflammation plays an important role in gout. The uptake of monosodium urate (MSU) crystals by macrophages can lead to activation of NOD-like receptors containing a PYD 3 (NLRP3) inflammasome, thus accelerating interleukin (IL)-1ß production. Reactive oxygen species (ROS) promoted development of the inflammatory process through NLRP3 inflammasome. Our study aimed to find a food-derived compound to attenuate gout pain via the specific inhibition of the NLRP3 inflammasome in macrophages. METHODS: CD-1 mice were used to evaluate the degree of pain and the swelling dimension of joints after an intra-articular (IA) MSU injection in the ankle. The murine macrophage cell line Raw 264.7 was used to investigate the effects of procyanidins and the mechanism underlying such effects. Histological analysis was used to measure the infiltration of inflammatory cells. ROS produced from Raw 264.7 cells were evaluated by flow cytometry. Cell signaling was measured by Western blot assay and immunofluorescence. RESULTS: Procyanidins significantly attenuated gout pain and suppressed ankle swelling. Procyanidins also inhibited MSU-induced activation of the NLRP3 inflammasome and increase of IL-1ß. Furthermore, procyanidins decreased ROS levels in Raw 264.7 cells. CONCLUSIONS: Suppression of the NLRP3 inflammasome in macrophages contributes to the amelioration of gout pain by procyanidins.
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Anti-Inflamatórios/uso terapêutico , Antioxidantes/toxicidade , Extrato de Sementes de Uva/uso terapêutico , Inflamação/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Dor/complicações , Proantocianidinas/uso terapêutico , Animais , Tornozelo/fisiopatologia , Colchicina/análogos & derivados , Colchicina/farmacologia , Citocinas/metabolismo , Gota/induzido quimicamente , Gota/complicações , Inflamação/induzido quimicamente , Inflamação/complicações , Lipopolissacarídeos/farmacologia , Camundongos , Dor/tratamento farmacológico , Dor/etiologia , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Ácido Úrico/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Activated astrocytes release matrix metalloproteinase-2/9 (MMP-2/9) to induce central sensitization and maintain neuropathic pain. However, the mechanisms involved in the activation of MMP-2/9 on astrocytes during pain remain poorly understood. Meanwhile, there is a lack of effective treatment to inhibit the activation of MMP-2/9 on astrocytes. In this study, we aim to investigate the effect of tetramethylpyrazine (TMP), a natural compound with analgesic effects but unknown mechanisms, on MMP-2/9 in neuropathic pain. METHODS: The nociception was assessed by measuring the incidence of foot withdrawal in response to mechanical indentation in rats (n = 6). Cell signaling was assayed using western blotting (n = 6) and immunohistochemistry (n = 5). The astrocyte cell line C8-D1A was cultured to investigate the in vitro effects. RESULTS: TMP significantly attenuated the maintenance of chronic constrictive injury (CCI)-induced neuropathic pain, inhibited the activation of astrocytes, and decreased the expression of MMP-2/9. Furthermore, our results indicated that TMP could selectively suppress JNK activity but had no notable effects on ERK and p38. Our study also revealed that the effect of TMP may be dependent on the inhibition of TAK1. CONCLUSIONS: Inhibition of astrocyte activation in the spinal cord by tetramethylpyrazine may have utility in the treatment of CCI-induced neuroinflammation, and our results further implicate JNK-MMP-2/9 as a novel target for the attenuation of neuropathic pain.
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Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/administração & dosagem , Neuralgia/tratamento farmacológico , Pirazinas/administração & dosagem , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/enzimologia , Células Cultivadas , Injeções Espinhais , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Neuralgia/enzimologia , Ratos , Ratos Sprague-Dawley , Vasodilatadores/administração & dosagemRESUMO
The increased cap-independent translation of anti-apoptotic proteins is involved in the development of drug resistance in lung cancer but signalling events regulating this are poorly understood. Fibroblast growth factor 2 (FGF-2) signalling-induced S6 kinase 2 (S6K2) activation is necessary, but the downstream mediator(s) coupling this kinase to the translational response is unknown. Here, we show that S6K2 binds and phosphorylates hnRNPA1 on novel Ser4/6 sites, increasing its association with BCL-XL and XIAP mRNAs to promote their nuclear export. In the cytoplasm, phosphoS4/6-hnRNPA1 dissociates from these mRNAs de-repressing their IRES-mediated translation. This correlates with the phosphorylation-dependent association of hnRNPA1 with 14-3-3 leading to hnRNPA1 sumoylation on K183 and its re-import into the nucleus. A non-phosphorylatible, S4/6A mutant prevented these processes, hindering the pro-survival activity of FGF-2/S6K2 signalling. Interestingly, immunohistochemical staining of lung and breast cancer tissue samples demonstrated that increased S6K2 expression correlates with decreased cytoplasmic hnRNPA1 and increased BCL-XL expression. In short, phosphorylation on novel N-term sites of hnRNPA1 promotes translation of anti-apoptotic proteins and is indispensable for the pro-survival effects of FGF-2.
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Núcleo Celular/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Proteínas 14-3-3/metabolismo , Transporte Ativo do Núcleo Celular , Linhagem Celular , Células HEK293 , Ribonucleoproteína Nuclear Heterogênea A1 , Humanos , Transdução de Sinais , Sumoilação , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMO
Protein-tyrosine kinase C-terminal Src kinase (Csk) was originally purified as a kinase for phosphorylating Src and other Src family kinases. The phosphorylation of a C-terminal tyrosine residue of Src family kinases suppresses their kinase activity. Therefore, most physiological studies regarding Csk function have been focused on Csk as a negative regulator of Src family tyrosine kinases and as a potential tumor suppressor. Paradoxically, the protein levels of Csk were elevated in some human carcinomas. In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus. We demonstrate that Csk-mediated phosphorylation of eEF2 has no effect on its cytoplasmic function in regulating protein translation. However, phosphorylation of eEF2 enhances its proteolytic cleavage and the nuclear translocation of the cleaved eEF2 through a SUMOylation-regulated process. Furthermore, we show that cleaved fragments of eEF2 can induce nuclear morphological changes and aneuploidy similar to those in cancer cells, suggesting that there is an additional mechanism for Csk in tumorigenesis through regulation of eEF2 subcellular localization.
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Núcleo Celular/metabolismo , Fator 2 de Elongação de Peptídeos/metabolismo , Quinases da Família src/metabolismo , Transporte Ativo do Núcleo Celular , Aneuploidia , Animais , Western Blotting , Proteína Tirosina Quinase CSK , Núcleo Celular/genética , Células Cultivadas , Embrião de Mamíferos/citologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Citometria de Fluxo , Células HEK293 , Células HeLa , Humanos , Camundongos , Camundongos Knockout , Fator 2 de Elongação de Peptídeos/genética , Fosforilação , Proteólise , Interferência de RNA , Proteína SUMO-1/genética , Proteína SUMO-1/metabolismo , Especificidade por Substrato , Sumoilação , Quinases da Família src/genéticaRESUMO
To determine age-related alterations in vortex veins in healthy subjects. A total of 228 healthy subjects (aged 4 to 86 years) were recruited and divided into four groups (G1, <21 years; G2, 21-40 years; G3, 41-60 years; and G4, 61-86 years). The clinical characteristics of the participants were recorded, and parameters including the number of vortex vein roots (NVVR), the central vortex vein diameter (CVVD), the mean root area of the vortex vein (MRAVV), and the weighted mean of the thickest branch diameter (WMTBD) were obtained by marking the vortex veins on indocyanine green angiography (ICGA). The NVVR in the age group over 60 years old was significantly lower than that in other age groups (P < 0.05). The CVVD, MRAVV, and WMTBD of all age groups increased with increasing age (P < 0.05). The NVVR was unevenly distributed among the quadrants (P < 0.001). The proportions of type four vortex veins (complete systems including ampulla) and anastomotic branches of the vortex veins were significantly increased in elderly participants over 50 years of age (P < 0.05). Subfoveal choroidal thickness was significantly correlated with age, NVVR, CVVD and MRAVV (P < 0.05). This is the first study to reveal age-related alterations in vortex veins on ICGA in a healthy population. Aging may lead to partial vortex occlusion and residual vortex dilation. As age increases, anastomotic branches increasingly appear between the originally independent vortex veins. Translational relevance: Aging may lead to partial vortex occlusion and residual vortex dilation.
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AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.
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OBJECTIVE: To detect the expression of prostate cancer antigen-1 (PCA-1) in prostate cancer, and to analyze the effects of downregulation of PCA-1 expression on malignant biological behavior of prostate cancer LNCaP cells, and to explore their possible molecular mechanisms. METHODS: PCA-1-siRNA and control siRNA were transfected into LNCaP cells with lipofectamine 2000. The cell cycle, proliferation and migration were determined by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry and Transwell chambers, respectively. Western blotting was used to detect the expression of cyclin E, matrix metallopeptidase 9 (MMP-9) and p21. Immunohistochemistry was used to detect the expression of PCA-1 protein in 126 cases of prostate cancer and 88 cases of benign prostatic hyperplasia (BPH). RESULTS: The positive rate of PCA-1 expression was 77.8% (98/126) in prostate cancer, and 10.2% (9/88) in BPH, and its expression was not significantly related to age, prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) score (P > 0.05), and was associated with Gleason score, TNM staging and bone metastasis (P < 0.05). Downregulation of PCA-1 expression inhibited cell proliferation, arrested cell cycle at S phase and decreased cell migration of LNCaP cells. The downregulation of PCA-1 expression decreased the expression of Bcl-xl, cyclin E and MMP-9 proteins, but increased the expression of p21 proteins. CONCLUSIONS: PCA-1 may play an important role in the development of prostate cancer. The downregulation of PCA-1 expression can lead to changes in the proliferation, cell cycle and migration of prostate cancer LNCaP cells, and these effects may be associated with the decrease of Bcl-xl, cyclin E and MMP-9 proteins and increase of p21 protein.
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Antígenos de Neoplasias/metabolismo , Ciclo Celular , Movimento Celular , Proliferação de Células , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Linhagem Celular Tumoral , Ciclina E/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Oncogênicas/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , RNA Interferente Pequeno/genética , Transfecção , Proteína bcl-X/metabolismoRESUMO
There are differences in vortex vein engorgement and appearance in polypoid choroidal vasculopathy (PCV), age-related macular degeneration (AMD), and healthy eyes. The present study aimed to use indocyanine green angiography (ICGA) to find a simple, clinically meaningful method for evaluating the filling degree of vortex veins in various eye diseases. Participant clinical characteristics were recorded. The number of vortex veins (NVV), central vortex vein diameter (CVVD), mean root area of the vortex vein (MRAVV), mean diameter of the thickest peripheral branch (MDPTB), subfoveal choroidal thickness and percentage of vortex vein anastomosis (PVVA) were obtained by marking the vortex veins on ICGA. The proportion of subretinal haemorrhage and the numbers and types of vortex veins in each quadrant were counted separately. The CVVD and MDPTB were significantly increased in the PCV compared with those in the AMD group (P<0.05). The CVVD, MRAV, and PVVA were significantly increased in the PCV compared with those in the healthy group (P<0.05). The type IV vortex vein (complete with ampulla) proportion was the lowest while the type I (vortex vein absent) proportion was the highest in the PCV group (P<0.001). NVV in the inferior-temporal region was increased in the PCV compared with that in the AMD group (P=0.034). Subretinal haemorrhage occurred in the inferior temporal choroid in 47.62% of examined eyes in PCV group, and in the superior temporal choroid in 23.81% of the PCV group, with significant differences between the quadrants (P<0.001). Vortex vein engorgement and shape differed significantly between PCV, AMD and healthy eyes. The vortex vein branches in PCV eyes were significantly dilated in the posterior pole; moreover, the peripheral choroid and the lower proportion of type IV vortex veins may be pathognomonic for PCV.
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Protein modification is critical for the regulation of protein functions. Cross-talks among different types of protein modifications should yield concerted and coordinated regulatory networks for physiological functions. Here we have employed system-wide and quantitative phosphoproteomics analyses to reveal a global cross-talk for SUMOylation-modulated phosphorylation. Furthermore, as specific examples, we have shown that the α subunit of casein kinase II is SUMOylated and that this affects the phosphorylation of its substrates. SUMO-regulated phosphorylation is involved in cell cycle control. Our data demonstrate an interplay between protein SUMOylation and phosphorylation and imply a regulatory role for this SUMOylation-modulated phosphorylation.
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Fosfoproteínas/metabolismo , Proteômica , Proteína SUMO-1/fisiologia , Sequência de Bases , Ciclo Celular/fisiologia , Linhagem Celular , Cromatografia em Gel , Primers do DNA , Humanos , Fosforilação , Sumoilação , Espectrometria de Massas em TandemRESUMO
Lichens are important sources of versatile bioactive compounds. Two new dibenzofurans (1-2), a multi-substituted single benzene ring (3), and two organic acid compounds (4-5) along with 25 known compounds (6-30) were isolated from the lichen Usnea diffracta Vain. Their structures were identified by physicochemical properties and spectral analyses. Compounds 1-30 were tested for inhibitory activities against Staphylococcus aureus, Escherichia coli, and Candida albicans by the disk diffusion method and microdilution assay respectively. Compound 3 showed moderate inhibitory activities against S. aureus and E. coli with the inhibition zone (IZ) of 6.2 mm and 6.3 mm, respectively. Depside 10 exhibited good activity against S.aureus and C. albicans with 6.6 mm and 32 µg/ml, respectively. The acetylcholinesterase inhibitory activities of compounds 1, 2, and 6-8 with the characteristic dibenzofuran scaffold were evaluated var anti-AChE assay and a molecular docking study. Compound 2 could better inhibit AChE at the concentration of 0.3 µmol/ml with a value of 61.07 ± 0.85%. The molecular docking study also demonstrated that compound 2 had the strongest binding affinity among the five dibenzofurans, and the "-CDOCKER Energy" value was 14.4513 kcal/mol.
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AIM: To identify the predictive factors and laser photocoagulation associated with the use of silicone oil as endotamponade during primary diabetic vitrectomy. METHODS: The medical and surgical records of 690 patients (798 eyes) who underwent primary diabetic vitrectomy at a tertiary eye hospital in China from January 2018 to December 2018 were reviewed in this retrospective cohort study. The patients' baseline characteristics and preoperative treatments were recorded. The binary Logistic regression model was used to evaluate the risk factors for the use of silicone oil as endotamponade agent during primary vitrectomy for proliferative diabetic retinopathy (PDR)-related complications. RESULTS: Among 690 patients with mean age of 52.1±10.5y (range: 18-85y), 299/690 (43.3%) were female. The 31.6% of the eyes received preoperative laser treatment, and 72.4% of the eyes received preoperative anti-VEGF adjuvant therapy. Non-clearing vitreous haemorrhage (VH) alone or combined with retinal detachment was the main surgical indication (89.5%) for primary vitrectomy. Silicone oil was used as endotamponade in 313 (39.2%) eyes. Lack of preoperative laser treatment [odds ratio (OR) 0.66, 95% confidence interval (CI): 0.48-0.92; P=0.015] and older age (OR 0.96, 95%CI: 0.95-0.98; P<0.001) were predictors of silicone oil tamponade during primary vitrectomy for PDR. CONCLUSION: The lack of preoperative laser treatment is a significant predictor of silicone oil tamponade during primary vitrectomy for PDR. However, the severity of PDR relevant to silicone oil use should be further evaluated.
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AIM: To investigate the rates of emulsification in silicone oil (SO) tamponades of differing viscosities used during pars plana vitrectomy (PPV) in the treatment of complicated vitreoretinal diseases. METHODS: This study was a prospective randomized clinical trial. Totally 290 cases with greater likelihoods of secondary detachment were included and randomly grouped into either Siluron 2000 (n=143) or Siluron 5000 (n=147) SO tamponades with 23-gauge PPV. Patient follow-ups and data analyses were conducted 1, 3, 6, and 12mo post-surgery. RESULTS: The time of the SO emulsification ranged from 1 to 17mo, with a mean of 7.3±4.2mo. The Siluron 5000 group showed a slower emulsification rate in comparison to the Siluron 2000 group. The Siluron 2000 group took a shorter time to show signs of emulsification, necessitating earlier SO removal. However, there were no significant differences in the occurrence of complications, including secondary retinal detachment, cataract, corneal abnormality, high intraocular pressure and hypotony. CONCLUSION: The Siluron 2000 SO tamponade shows a faster rate of emulsification than the Siluron 5000 SO, necessitating earlier removal. Both groups show similar results in terms of anatomical success and visual acuity outcome, and there is no significant difference between the SOs regarding the occurrence of complications.
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BACKGROUND: Currently, whether and when intraocular pressure (IOP)-lowering medication should be used in glaucoma suspects with high myopia (GSHM) remains unknown. Glaucoma suspects are visual field (VF) defects that cannot be explained by myopic macular changes or other retinal and neurologic conditions. Glaucoma progression is defined by VF deterioration. Here we describe the rationale, design, and methodology of a randomized controlled trial (RCT) designed to evaluate the effects of medically lowering IOP in GSHM (GSHM study). METHODS: The GSHM study is an open-label, single-center, RCT for GSHM. Overall, 264 newly diagnosed participants, aged 35 to 65 years, will be recruited at the Zhongshan Ophthalmic Center, Sun Yat-sen University, between 2020 and 2021. Participants will be randomly divided into two arms at a 1:1 ratio. Participants in the intervention arm will receive IOP-lowering medication, while participants in the control arm will be followed up without treatment for 36 months or until they reach the end point. Only one eye per participant will be eligible for the study. If both eyes are eligible, the eye with the worse VF will be recruited. The primary outcome is the incidence of glaucoma suspect progression by VF testing over 36 months. The secondary outcomes include the incidence of changes in the optic nerve head morphology including the retinal nerve fiber layer, and retinal ganglion cell-inner plexiform layer loss, progression of myopic maculopathy, visual function loss, and change in the quality of life. Statistical analyses will include baseline characteristics comparison between the intervention and control groups using a two-sample t-test and Wilcoxon rank sum test; generalized linear models with Poisson regression for the primary outcome; Kaplan-Meier curve and log-rank test for the incidence of the secondary outcome; and longitudinal analyses to assess trends in outcomes across time. DISCUSSION: To the best of our knowledge, the GSHM study is the first RCT to investigate the impact of medically lowering IOP in GSHM. The results will have implications for the clinical management of GSHM. TRIAL REGISTRATION: ClinicalTrials.gov NCT04296916 . Registered on 4 March 2020.
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Glaucoma , Miopia , Progressão da Doença , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular , Miopia/diagnóstico , Miopia/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos da VisãoRESUMO
BACKGROUND: Previous studies showed that alpha-1,2-fucosyltransferase (HT), decay accelerating factor (DAF), and CD59 have an inhibitory effect on the immunological rejection of xenogenic transplantation. METHODS: To investigate their possible synergistic effects in suppression of heterogeneic transplantation, we produced transgenic mouse lines expressing human HT, DAF, and/or CD59 by the standard pronuclear injection approach. PCR and Southern blot were used to identify the transgenic founder lines. Flow cytometry confirmed the high-level expression of HT, DAF, or CD59 in the transgenic mice. RESULTS: The deposition of IgM, C3c, or C9 in the cardiac vascular endothelial cells of the HT, HT/CD59, and/or DAF multiple positive transgenic mice was markedly decreased. The survival time and function of the hearts of the co-transgenic mice were significantly longer and higher than that of the single HT-positive transgenic mice (P < 0.05). CONCLUSION: The mice co-expressing HT/DAF or HT/CD59 could resist the hyperacute rejection better than those expressing HT alone. It is feasible to use HT and C-reactive proteins co-transgenic tissues to resist hyperacute rejection and xenograft rejection.
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Anticorpos Heterófilos/metabolismo , Antígenos CD55/metabolismo , Antígenos CD59/metabolismo , Fucosiltransferases/metabolismo , Transplante de Coração/imunologia , Transplante Heterólogo/imunologia , Animais , Antígenos CD55/genética , Antígenos CD59/genética , Complemento C3c/metabolismo , Complemento C9/metabolismo , Endotélio Vascular/imunologia , Fucosiltransferases/genética , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunoglobulina M/metabolismo , Camundongos , Camundongos Transgênicos , Miocárdio/imunologiaRESUMO
OBJECTIVE: To assess the clinical efficacy and safety of three different methods of anesthesia during transrectal ultrasound guided prostate biopsy. METHODS: From July 2006 to October 2008, a total of 120 patients who underwent 12-core prostate biopsy with transrectal ultrasound guidance because of elevated prostate specific antigen and/or abnormal digital rectal examination were randomized into 4 groups, each group consisted of 30 patients. Group A received no anesthesia. Group B received an injection of 10 ml dose of 1% lidocaine (5 ml per side) into the region of the prostatic vascular pedicle at the prostate base just lateral to the junction between the seminal vesicle and prostate on each side for periprostatic nerve block (PNB). Group C received intrarectal lidocaine gel plus PNB. Group D received an injection of 4 ml dose of 1% lidocaine (2 ml per side) into 2 sites of the right and left sides of prostate for intraprostatic anesthesia plus PNB. The efficiency of anesthesia was assessed by a visual analog pain scale (VAS). All patients were followed up within one week for the evaluation of complications. RESULTS: The combination of intraprostatic anesthesia and PNB provided significantly better pain control than PNB alone. According to VAS, only group C (2.7 +/- 1.1) scores showed significantly better pain control than other groups (P < 0.05) during probe insertion, and only group D (3.9 +/- 1.3) scores showed significantly better pain control than other groups (P < 0.05) during biopsy. No difference was observed regarding the complications rate in the 4 groups (P > 0.05). CONCLUSIONS: Combination of intraprostatic anesthesia and PNB is effective and safe technique during transrectal ultrasound guided prostate biopsy without increasing the incidence of complications. PNB or PNB plus intrarectal lidocaine gel couldn't significantly reduce pain during biopsy.
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Anestesia/métodos , Biópsia por Agulha , Próstata/patologia , Idoso , Método Duplo-Cego , Seguimentos , Humanos , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Bloqueio NervosoRESUMO
PURPOSE: To introduce and evaluate a sutureless technique by using a polymethyl methacrylate (PMMA) ring and fibrin sealant to fix an amniotic membrane (AM) patch on the ocular surface as a therapeutic contact lens in a rabbit model. METHODS: PMMA rings were fabricated by duplicating an impression of a rabbit conjunctival fornix. The central cornea of the left eye in 16 rabbits was deepithelialized (diameter = 10 mm). A human AM patch was fixed to the ocular surface by using either a PMMA ring and fibrin sealant or interrupted 10-0 nylon sutures. The fibrin sealant was used to create the PMMA ring-AM complex but not to attach the AM/PMMA ring to the ocular surface. The rabbits were followed up with slit-lamp examination and fluorescein staining for 7 days. Reepithelialization and complications were recorded. RESULTS: The corneal epithelial defect was recovered in each rabbit of both groups after 5 days. In the sutureless group, all membranes remained in place and intact during the follow-up period. One eye was noted to have a partial conjunctival epithelial defect caused by exposure to the PMMA ring. In contrast, >50% of rabbits in the interrupted suture group exhibited complications including conjunctival edema, suture loosening, patch detachment, bleeding, and conjunctival epithelial defects. CONCLUSIONS: The sutureless technique that uses a PMMA ring and fibrin sealant for AM patch placement has a lower incidence of complications than the interrupted suture method. This sutureless technique may promote increased clinical use of AM patch by alleviating patients' pain and shortening surgical time.
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Âmnio/transplante , Lentes de Contato , Adesivo Tecidual de Fibrina/administração & dosagem , Polimetil Metacrilato , Próteses e Implantes , Técnicas de Sutura , Adesivos Teciduais/administração & dosagem , Animais , Epitélio Corneano/fisiologia , Humanos , Modelos Animais , Implantação de Prótese , Coelhos , Regeneração , CicatrizaçãoRESUMO
AIM: To analyze peripapillary atrophy ß/γ zone (PPA-ß/γ) and the optic disc ovality index, and to assess their associations with the axial length (AL), refractive error, best corrected visual acuity (BCVA), choroidal thickness (CT), and age in highly myopic eyes. METHODS: This was a retrospective observational case series. The study included 667 patients consecutively examined for highly myopic eyes [spherical equivalent ≤-6.0 diopters (D) and AL≥26 mm] with or without myopic retinopathy. Each patient went through a comprehensive ophthalmological examination that included spectral domain optical coherence tomography (SD-OCT) of the macula, A-mode ultrasonography, and a cycloplegic refraction test. The ovality index and PPA-ß/γ area were measured from optic disc photographs. RESULTS: A significant association was seen between PPA-ß/γ area and the ovality index (P=0.000, r=-0.232). The PPA-ß/γ area increased significantly with a longer AL, older age, worse BCVA, higher refractive error, and thinner choroid (P<0.01). The oval disc was significantly correlated with a longer AL, older age, worse BCVA, higher refractive error, larger PPA-ß/γ area, and thinner choroid (P<0.01). CONCLUSION: The PPA-ß/γ zone and ovality index in highly myopic eyes show distinct associations with the AL, refractive error, BCVA, age, and CT.
RESUMO
AIM: To examine the expression of prostate cancer antigen-1 (PCA-1) in prostate cancer (PCa) and to validate it as a potential marker for diagnosis of PCa. METHODS: In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia (BPH), 16 high-grade prostatic intraepithelial neoplasm (HG-PIN), 74 PCa and 34 other malignant carcinoma specimens. The level of PCA-1 expression was semiquantitatively scored by assessing both the percentage and intensity of PCA-1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. RESULTS: PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score (P < 0.05), and was unrelated to other clinical parameters of PCa (all P > 0.05). CONCLUSION: The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.
Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Biópsia , DNA Complementar/metabolismo , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasia Prostática Intraepitelial/diagnóstico , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: To investigate the expression of prostate cancer antigen-1 (PCA-1) in different prostate tissues and analyze its correlation with the clinical parameters of prostate cancer (PCa). METHODS: The expression of PCA-1 mRNA was detected by RT-PCR in the samples from 45 cases of PCa with various clinico-pathologic characteristics, 30 cases of high-grade prostatic intraepithelial neoplasia (HG-PIN), 43 cases of BPH and 39 cases of other carcinoma tissues. The correlation of PCA-1 mRNA expression with the clinical parameters of PCa was statistically analyzed and the PCA-1 expression was examined in different samples by immunohistochemistry. RESULTS: The positive expression rate of PCA-1 mRNA was 88.9% and 60.0% and that of PCA-1 protein was 84.4% and 50.0% in the patients with PCa and HG-PIN, respectively. PCA-1 mRNA and PCA-1 proteins were not expressed in the BPH and other carcinoma tissues. The expression of PCA-1 mRNA was unrelated with the clinical parameters of PCa (P > 0.05). CONCLUSION: It is suggested that PCA-1 is a PCa-specific gene and its expression is unrelated to the clinical parameters of PCa. It might serve as a specific biomarker for the early diagnosis of PCa.