RESUMEN
Objective: To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis (P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods: A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 µg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results: At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, Pï¼0.05) and mild/moderate dysplasia (median 2.00, Pï¼0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1ß [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm2), the thickness of the esophageal wall (median 172.52 µm), the foci of hyperproliferation (median 1.00, Pï¼0.05), and mild/moderate dysplasia (median 1.00, Pï¼0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1ß [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions: P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.
Asunto(s)
4-Nitroquinolina-1-Óxido , Celecoxib , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Ratones Endogámicos C57BL , Porphyromonas gingivalis , Microambiente Tumoral , Animales , Ratones , Neoplasias Esofágicas/microbiología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/microbiología , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Celecoxib/farmacología , Inflamación , Infecciones por Bacteroidaceae/microbiología , Interleucina-6/metabolismo , Antibacterianos/farmacología , Factor de Transcripción STAT3/metabolismo , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Esófago/microbiología , Esófago/patología , Esofagitis/microbiología , Esofagitis/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Carcinoma de Células Escamosas/microbiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismoRESUMEN
We have designed and fabricated high-performance single-photon avalanche diodes (SPADs) by using 0.18-µm high-voltage CMOS technology. Without any technology customization, the SPADs have low dark-count rate, high photon-detection probability, low afterpulsing probability, and acceptable timing jitter and breakdown voltage. Our design provides a low-cost and high-performance SPAD for various applications.
RESUMEN
BACKGROUND: Garzê and Aba form the second largest Tibetan-inhabited area of China. Blood services have never been reported for this region before. OBJECTIVE: To assess the current situation and analyse whether a safe and adequate blood supply has been developed in both Garzê and Aba. METHODS: We conducted a longitudinal survey covering the period 2011-2016. The subjects of interest were recruited from non-remunerated voluntary donation, blood testing, clinical transfusion practices and infrastructure of local blood service systems. RESULTS: The donation rate and blood collection volume were below the average levels of both the Sichuan Province and mainland China. Component therapy was widely used, but inappropriate usage of whole blood existed. A lack of national specific standards for people on the plateaus led to local blood transfusions being conducted without full clinical assessment. Endemic and frequently occurring disease, such as hydatid disease and gastrointestinal disease, were inevitable risks for blood utilisation and safety. The potential influence of religious belief and traditions, like 'male-leaving marriages', of Tibetans on donor recruitment and blood safety requires further research. CONCLUSIONS: A relatively safe and complete blood service system has been developed in this region. However, there is still an urgent need for comprehensive and effective support from the government in terms of policies and finance. As an epidemic area of hydatid disease and sexually transmitted disease, this region needs to emphasise public health measures, such as blood safety and inappropriate usage of blood products.
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Donantes de Sangre , Atención a la Salud , Encuestas y Cuestionarios , Atención a la Salud/organización & administración , Atención a la Salud/normas , Femenino , Humanos , Estudios Longitudinales , Masculino , TibetRESUMEN
Objective: To discuss the etiology, clinical features and treatment principles of the orbital and periorbital abscess. Methods: A retrospective case series of 17 cases with orbital and periorbital abscess between July 2010 and November 2015 were conducted. All patients(,) clinical data including medical history, etiology, abscess location, paranasal sinus involvement, eye involvement, microbiological test results, imaging features, treatment and prognosis were summarized and analyzed. Results: In all 17 patients, there were 10 males and 7 females with age from 3.0 to 71.0 years (the average age was 33.9 years).Eight patients(,) bacterial cultures of the pus and secretion were positive in all 17 patients. Orbital and periorbital abscess patients could manifest decreased vision, redness and swelling of eyelid, conjunctival congestion and edema, ocular motility disorders, displacement of eyeball, increased orbital pressure, abscess rupture etc. CT showed us the soft tissue mass, accompanied with sinusitis or paranasal sinus mass. MR performed with the long T(1) and T(2) signals. The signals of the abscess cavity were not uniform. For the etiology,11 cases were secondary to sinusitis, including 1 case of diabetes; 2 cases with orbital fractures.One case was secondary to orbital fracture repairment surgery. One case was secondary to the remnant of sequestrum and foreign bodys in the wound after repairment surgery. One case was injured by the hard object. One case was secondary to paranasal sinuses large B-cell lymphoma. One case had diabetic history and the blood sugar was controlled unstablly. For the treatment, 7 cases were treated by the drainage surgery which was performed via the sinus with endoscopic and abscess resection performed via the skin.Two cases were treatment by the abscess resection only.One case was treated by the drainage surgery performed via the sinus with endoscopic only. Six cases were treated by the drainage surgery performed via the skin. One case was only administered intravenous antibiotic. Sixteen cases acquired well prognosis without serious complications except 1 case which occurred central retinal artery and vein occlusion. Conclusions: The orbital and periorbital abscess is mainly a complication of paranasal sinus infection, or secondary to trauma, surgery, tumor, etc; Orbital and periorbital abscess always manifest inflammatory neoplastic clinical features, the key of the diagnosis is to make sure the etiology; Incision and drainage of the abscess is the main treatment method when necessary. We can do the surgery with other departments to avoid the occurrence of serious complications.(Chin J Ophthalmol, 2017, 53: 588-593).
Asunto(s)
Absceso , Enfermedades Orbitales , Sinusitis , Absceso/etiología , Absceso/terapia , Adulto , Antibacterianos , Drenaje , Femenino , Humanos , Masculino , Enfermedades Orbitales/etiología , Enfermedades Orbitales/terapia , Senos Paranasales , Estudios Retrospectivos , Sinusitis/etiología , Sinusitis/terapiaRESUMEN
When Chinese hamster ovary cells were treated with ultraviolet (UV) light or methyl methanesulfonate (MMS), a large number of DNA strand breaks could be detected by alkaline elution. These strand breaks gradually disappeared if the treated cells were allowed to recover in a drug-free medium. The presence of nickel or arsenite during the recovery incubation retarded the disappearance of UV-induced strand breaks, whereas the disappearance of MMS-induced strand breaks was retarded by the presence of arsenite or of luminol, a new inhibitor for poly(ADP-ribose) synthetase. Luminol, however, had no apparent effect on the repair of UV-induced DNA strand breaks, and nickel had no effect on the repair of MMS-induced DNA strand breaks. When UV- or MMS-treated cells were incubated in cytosine arabinofuranoside (AraC) plus hydroxyurea (HU), a large amount of low molecular weight DNA was detected by alkaline sucrose sedimentation. The molecular weight of these DNAs increased if the cells were further incubated in a drug-free medium. This rejoining of breaks in cells pretreated with UV plus AraC and HU was inhibited by nickel and by arsenite, but not by luminol. The rejoining of breaks in cells pretreated with MMS plus AraC and HU was inhibited by luminol and by arsenite, but not by nickel. These results suggest that different enzymes may be used in DNA resynthesis and/or ligation during the repairing of UV- and MMS-induced DNA strand breaks, and that nickel, luminol, and arsenite may have differential inhibitory effects on these enzymes.
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Arsenitos/farmacología , Reparación del ADN/efectos de los fármacos , Luminol/farmacología , Níquel/farmacología , Rayos Ultravioleta , Alquilación , Animales , Células CHO , Cricetinae , Daño del ADN , Reparación del ADN/efectos de la radiación , Metilmetanosulfonato/farmacologíaRESUMEN
The cytotoxic effect of arsenite seems to be inversely related to the intracellular glutathione (GSH) content, and GSH seems to facilitate the metabolism of arsenic in cell. Arsenite is also known to induce chromosome aberration, to enhance the cytotoxicity and clastogenicity of ultraviolet (UV) light, and to inhibit UV-induced DNA repair. We have investigated whether these toxic effects of arsenite and the cellular arsenic content are also modulated by the intracellular GSH. A 2-h pretreatment of the cultured ovary (CHO) cells with GSH reduced the clastogenicity and cytotoxicity of arsenite. The enhancing effects of arsenite on chromosome aberrations and cell destruction induced by UV were also reduced by a 2-h pretreatment with GSH. The inhibitory effect of arsenite on the strand-break rejoining during UV-induced DNA repair was reduced by GSH pretreatment and was enhanced by pretreatment with buthionine sulfoximine, which is known to deplete the cellular GSH. The cellular arsenic content was reduced by GSH pretreatment and increased by buthionine sulfoximine pretreatment. GSH given before or simultaneously with arsenite, effectively reduced the clastogenicity and coclastogenicity of arsenite. GSH given after treatment with arsenite decreased the cellular arsenic content, and increased the cell survival, but did not reduce the clastogenicity or the coclastogenicity of arsenite.
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Arsénico/toxicidad , Arsenitos , Glutatión/farmacología , Animales , Antimetabolitos/farmacología , Arsénico/antagonistas & inhibidores , Butionina Sulfoximina , Células CHO , Supervivencia Celular/efectos de los fármacos , Aberraciones Cromosómicas , Cricetinae , Cricetulus , Metionina Sulfoximina/análogos & derivados , Metionina Sulfoximina/farmacología , Rayos UltravioletaRESUMEN
Nickel, a human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity, and sister-chromatid exchanges (SCE) induced by ultraviolet (UV) light but not by methyl methanesulfonate (MMS). To verify that the cocytotoxicity and cogenotoxicity of nickel are correlated with its inhibition on DNA repair, the effects of nickel on the DNA repair induced by UV and by MMS have been investigated. Our analyses of DNA repair of single-strand breaks by alkaline elution and alkaline sucrose sedimentation indicate that nickel inhibited the DNA repair in UV-treated, but not in MMS-treated cells. Therefore, the inhibition of DNA repair seems to play an important role in the cocytotoxicity and comutagenicity of nickel. However, the inhibition of DNA repair seems not to play a decisive role in enhancing SCE, because we have previously shown that arsenite inhibits the UV-induced DNA repair, but has no enhancing effect on the UV-induced SCE. Our results also show that nickel had obvious inhibitory effects on DNA ligation and postreplication repair, but had no apparent effect on nucleotide excision and DNA polymerization in the UV repair. The results of the DNA ligation inhibition by nickel in UV but not in MMS repair suggest that different ligases are used in the DNA repair of UV- and MMS-induced damages.
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Carcinógenos/toxicidad , Reparación del ADN/efectos de los fármacos , Metilmetanosulfonato/toxicidad , Níquel/toxicidad , Rayos Ultravioleta , Animales , Células CHO , Supervivencia Celular/efectos de los fármacos , Centrifugación por Gradiente de Densidad , Cricetinae , Citarabina/farmacología , ADN/análisis , ADN/efectos de los fármacos , ADN/efectos de la radiación , Hidroxiurea/farmacologíaRESUMEN
Heparin and plasmin were co-immobilized on collageno-elastic tubes (CETs) in order to develop a thromboresistant and fibrinolytic vascular prosthesis. The mutual interaction between heparin and plasmin both in the soluble and in the immobilized state was studied. The immobilization condition rendering maximum co-immobilized heparin and plasmin activity was identified to require heparin immobilization followed by plasmin immobilization. Soluble heparin exerts a positive synergistic effect on soluble plasmin. Immobilized heparin enhances plasmin loading on the CET as compared to the heparin-free graft. Heparin, in both the soluble or immobilized state, significantly decreases the Michaelis-Menten (M-M) parameter Km for immobilized plasmin over heparin-free immobilized plasmin. Furthermore, the M-M parameter Vmax for the immobilized plasmin in the presence of heparin decreases over heparin-free immobilized plasmin. These results suggest a decrease in the kinetic constant k3 for heparin-modified immobilized plasmin over the heparin-free form. Co-immobilized heparin-plasmin collagenous grafts represent a unique advance in the development of fibrinolytically active prostheses.
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Colágeno , Fibrinolisina/metabolismo , Heparina/metabolismo , Animales , Fibrinólisis , Glutamatos/metabolismo , Ovinos , PorcinosRESUMEN
A laboratory-scale multiphase hollow fiber membrane reactor was employed to investigate the lipase-catalyzed enzymatic resolution of racemic glycidyl butyrate. A mathematical formulation was developed to simulate the performance of this system. Model parameters were determined independently (except the effective rate constant, k(s)) and incorporated in the model simulations. In this study, two modes of operation are considered: subtractive resolution, in which the unreacted substrate is recovered in the organic stream; and product recovery, where the optically pure product of the enzymatic reaction is recovered in the aqueous stream. Good agreement was obtained between theoretical predictions and experimental results under a variety of conditions. The effect of mass transport limitations on the performance of this system was investigated. An increase in enzyme loading resulted in a higher Thiele modulus due to an elevated rate constant as well as a concomitant decrease in the effective diffusivity. Optical purity decreased in both subtractive resolution and product recovery at higher Thiele modulus with the effect being more pronounced in the product recovery mode. Finally, normalized plots were established to describe the effect of enzyme immobilization on both the effective enzymes activity and effective diffusivity.
RESUMEN
Complex glycerol kinase deficiency (CGKD) is a contiguous gene syndrome consisting of glycerol kinase deficiency together with Duchenne muscular dystrophy (DMD), congenital adrenal hypoplasia, and/or Aland Island eye disease. Deletion mapping of genomic DNA from patients with CGKD was carried out and allowed definitive ordering of loci DXS28 (C7), DXS68 (L1-4), and DXS67 (B24). Most reports have placed DXS68 centromeric to DXS28 and DXS67 on the basis of the initial mapping of the Iowa patient 3, but others have presented evidence consistent with the placement of DXS28 telomeric to DXS68 and DXS67. Through the use of DNA from CGKD patients with a variety of genomic deletions, this controversy is resolved and the order Xcen...DMD-DXS28-DXS68-DXS67...pter is definitively demonstrated.
Asunto(s)
Insuficiencia Suprarrenal/congénito , Albinismo/genética , Mapeo Cromosómico , Glicerol Quinasa/genética , Distrofias Musculares/genética , Fosfotransferasas/genética , Insuficiencia Suprarrenal/genética , Southern Blotting , Centrómero , Deleción Cromosómica , Análisis Mutacional de ADN , Glicerol Quinasa/deficiencia , Humanos , Masculino , Síndrome , Cromosoma XRESUMEN
Genomic DNA from five previously unreported patients with glycerol kinase deficiency (GKD), dystrophic myopathy, and adrenal insufficiency were studied with genomic probes and cDNA probes for the Duchenne muscular dystrophy (DMD) locus. These individuals, together with those reported by ourselves and others, show that patients with a contiguous gene syndrome involving the DMD, GK, and adrenal hypoplasia congenita (AHC) loci have a broader distribution of microdeletion breakpoints than those observed among patients with classical DMD. This study demonstrates the use of the DMD cDNA probes to delineate the centromeric deletion breakpoints for patients with Xp21 microdeletions extending beyond the DMD locus. It also shows the practical diagnostic application of the DMD cDNA probes when the diagnosis of GKD is entertained in a patient with known DMD and only DNA is available for study.