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The aim of the present study was to investigate the possibility of reducing the damage to the donor site while preserving the functional recovery of the dorsum of the hand following burn injury. An attempt was made to analyze the effect of a phased surgery approach on inflammatory indicators. A two-phase treatment was administered on a total of 64 patients with deep second-degree burns on the dorsum of the hand who were admitted to Guangzhou Red Cross Hospital between January 2020 and March 2023. During phase I treatment, the wounds were covered with xenogeneic (porcine) skin, followed by the application of autologous thin intermediate thickness skin grafts for wound repair in phase II treatment 1 week later. The surgical results, complications, patient satisfaction and inflammatory response indicators were then analyzed. The mean wound healing time of these patients was found to be 21.94 days without complications. The mean survival rate was 98.66%, and the overall satisfaction score of the patients was high. Finally, the white blood cell, C-reactive protein and IL-6 levels of these patients were continuously decreased 2 days preoperatively and 2 days postoperatively in phase I, and 2 days preoperatively and 2 days postoperatively in phase II. In combination, the effect of phased autologous skin grafting in patients with severe second-degree burns on the dorsum of the hand was ideal, as it significantly reduced inflammatory response and was beneficial to the functional recovery of the hand. Therefore, phased autologous skin grafting is worthy of wider application.
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OBJECTIVE: To evaluate the occurrence of aortic dilatation and its associated predictors with coarctation of the aorta (CoA) in infants using multi-slice computed tomography (MSCT). METHODS: The clinical data of 47 infantile patients with CoA diagnosed by MSCT and 28 infantile patients with simple ventricular septal defect were analyzed retrospectively. Aortic diameters were measured at six different levels, and aortic sizes were compared by z score. The coarctation site-diaphragm ratio was used to describe the degree of narrowing. Relevant clinical data were collated and analyzed. RESULTS: The dilation rate and z score of the ascending aorta in the severe CoA group were significantly higher than those in the mild CoA group (11 [52.38%] vs. 21 [80.77%], P=0.038 and 2.00 ± 0.48 vs. 2.36 ± 0.43, P=0.010). Pearson's correlation analysis found that the z score of the ascending aorta was negatively correlated with the coarctation site-diaphragm ratio value (r=-0.410, P=0.004). A logistic retrospective analysis found that an increased degree of coarctation was an independent predictor of aortic dilatation (adjusted odds ratio 0.002; 95% confidence interval 0.00-0.819; P=0.043). The z score of the ascending aorta in the severe CoA group was significantly higher than that in the ventricular septal defect group (P<0.05). CONCLUSION: Most infants with CoA can also have significant dilatation of the ascending aorta, and the degree of this dilatation is related to the degree of coarctation. Assessment of aortic diameter and related malformations by MSCT can predict the risk of aortic dilatation in infants with CoA.
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Coartação Aórtica , Comunicação Interventricular , Lactente , Humanos , Angiografia por Tomografia Computadorizada , Dilatação , Estudos Retrospectivos , Coartação Aórtica/diagnóstico por imagemRESUMO
Metalloporphyrins with open d-shell ions can drive biochemical energy cycles. However, their utilization in photoconversion is hampered by rapid deactivation. Mapping the relaxation pathways is essential for elaborating strategies that can favorably alter the charge dynamics through chemical design and photoexcitation conditions. Here, we combine transient optical absorption spectroscopy and transient X-ray emission spectroscopy with femtosecond resolution to probe directly the coupled electronic and spin dynamics within a photoexcited nickel porphyrin in solution. Measurements and calculations reveal that a state with charge-transfer character mediates the formation of the thermalized excited state, thereby advancing the description of the photocycle for this important representative molecule. More generally, establishing that intramolecular charge-transfer steps play a role in the photoinduced dynamics of metalloporphyrins with open d-shell sets a conceptual ground for their development as building blocks capable of boosting nonadiabatic photoconversion in functional architectures through "hot" charge transfer down to the attosecond time scale.
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BACKGROUND: Neonatal intrahepatic cholestasis due to citrin deficiency (NICCD) is an autosomal recessive disorder caused by SLC25A13 genetic mutations. We retrospectively analyzed 26 Chinese infants with NICCD (years 2014-2022) in Quanzhou City. METHODS: The plasma citrulline (CIT) concentration analyzed by tandem mass spectrometry (MS/MS), biochemical parameters and molecular analysis results are presented. RESULTS: Twelve genotypes were discovered. The relationship between the CIT concentration and genotype is uncertain. In total, 8 mutations were detected, with 4 variations, c.851_854delGTAT, c.615 + 5G > A, c.1638_1660dup and IVS16ins3kb, constituting the high-frequency mutations. Specifically, we demonstrated 2 patients with NICCD combined with another inborn errors of metabolism (IEM). Patient No. 22 possessed compound heterozygous mutations of c.615 + 5G > A and c.790G > A in the SLC25A13 gene accompanied by compound heterozygous variations of c.C259T and c.A155G in the PTS gene. Additionally, Patient No. 26 carried c.51C > G and c.760C > T in the SLC22A5 gene as well as c.615 + 5G > A and IVS16ins3kb in the SLC25A13 gene. CONCLUSIONS: We report a case of the simultaneous occurrence of primary carnitine deficiency (PCD) and NICCD.
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Colestase Intra-Hepática , Colestase , Citrulinemia , Doenças do Recém-Nascido , Transportadores de Ânions Orgânicos , Humanos , Lactente , Recém-Nascido , Proteínas de Ligação ao Cálcio/genética , China , Colestase Intra-Hepática/genética , Citrulinemia/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , Mutação , Transportadores de Ânions Orgânicos/genética , Estudos Retrospectivos , Membro 5 da Família 22 de Carreadores de Soluto/genética , Espectrometria de Massas em TandemRESUMO
ABSTRACT Objective: To evaluate the occurrence of aortic dilatation and its associated predictors with coarctation of the aorta (CoA) in infants using multi-slice computed tomography (MSCT). Methods: The clinical data of 47 infantile patients with CoA diagnosed by MSCT and 28 infantile patients with simple ventricular septal defect were analyzed retrospectively. Aortic diameters were measured at six different levels, and aortic sizes were compared by z score. The coarctation site-diaphragm ratio was used to describe the degree of narrowing. Relevant clinical data were collated and analyzed. Results: The dilation rate and z score of the ascending aorta in the severe CoA group were significantly higher than those in the mild CoA group (11 [52.38%] vs. 21 [80.77%], P=0.038 and 2.00 ± 0.48 vs. 2.36 ± 0.43, P=0.010). Pearson's correlation analysis found that the z score of the ascending aorta was negatively correlated with the coarctation site-diaphragm ratio value (r=-0.410, P=0.004). A logistic retrospective analysis found that an increased degree of coarctation was an independent predictor of aortic dilatation (adjusted odds ratio 0.002; 95% confidence interval 0.00-0.819; P=0.043). The z score of the ascending aorta in the severe CoA group was significantly higher than that in the ventricular septal defect group (P<0.05). Conclusion: Most infants with CoA can also have significant dilatation of the ascending aorta, and the degree of this dilatation is related to the degree of coarctation. Assessment of aortic diameter and related malformations by MSCT can predict the risk of aortic dilatation in infants with CoA.
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OBJECTIVE: To investigate the accuracy of aortic dimensions measured by Revolution™ computed tomography (CT) in infants with complex coarctation of the aorta (CoA) and to further analyze the utility of the degree of CoA in predicting the risk of prolonged postoperative cardiac intensive care unit stay. METHODS: A total of 30 infants with complex CoA who underwent surgical correction from January 2020 to July 2022 were retrospectively enrolled. General demographic data, preoperative imaging, and perioperative outcomes were collected. Univariate and multivariate analyses were performed to investigate predictors of prolonged postoperative cardiac intensive care unit stay, and the reliability of the CT measurements was assessed by the intraclass correlation coefficient. RESULTS: All infants were divided into a mild or severe CoA group. The duration of mechanical ventilation and cardiac intensive care unit stay in the mild CoA group were significantly lower than those in the severe CoA group. After multivariate analysis, we found that the degree of CoA and age at surgery were significant predictors of prolonged postoperative cardiac intensive care unit stay. The intraclass correlation coefficient between CT measurements and intraoperative measurements was between 0.937 and 0.975, and the measurement results had good reliability. CONCLUSION: CT angiography can provide a comprehensive and accurate preoperative evaluation of aortic dimensions measured in infants with complex CoA. The degree of CoA is an independent risk factor for prolonged postoperative cardiac intensive care unit stay in infants with complex CoA.
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Coartação Aórtica , Angiografia por Tomografia Computadorizada , Humanos , Lactente , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/cirurgia , Estudos Retrospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Unidades de Terapia Intensiva , Tempo de InternaçãoRESUMO
ABSTRACT Objective: To investigate the accuracy of aortic dimensions measured by Revolution™ computed tomography (CT) in infants with complex coarctation of the aorta (CoA) and to further analyze the utility of the degree of CoA in predicting the risk of prolonged postoperative cardiac intensive care unit stay. Methods: A total of 30 infants with complex CoA who underwent surgical correction from January 2020 to July 2022 were retrospectively enrolled. General demographic data, preoperative imaging, and perioperative outcomes were collected. Univariate and multivariate analyses were performed to investigate predictors of prolonged postoperative cardiac intensive care unit stay, and the reliability of the CT measurements was assessed by the intraclass correlation coefficient. Results: All infants were divided into a mild or severe CoA group. The duration of mechanical ventilation and cardiac intensive care unit stay in the mild CoA group were significantly lower than those in the severe CoA group. After multivariate analysis, we found that the degree of CoA and age at surgery were significant predictors of prolonged postoperative cardiac intensive care unit stay. The intraclass correlation coefficient between CT measurements and intraoperative measurements was between 0.937 and 0.975, and the measurement results had good reliability. Conclusion: CT angiography can provide a comprehensive and accurate preoperative evaluation of aortic dimensions measured in infants with complex CoA. The degree of CoA is an independent risk factor for prolonged postoperative cardiac intensive care unit stay in infants with complex CoA.
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Objective: To explore the accuracy and image quality of wide-detector revolution CT angiography combined with prospective ECG-triggered CT angiography in the diagnosis of congenital aortic arch anomalies in Chinese children. Methods: From January 2020 to July 2022, the clinical data of 57 children with congenital aortic arch anomalies confirmed by surgery were collected. All patients underwent CT angiography (CTA) with Revolution CT and transthoracic echocardiography (TTE) before the operation. The accuracy of CTA and TTE in the diagnosis of aortic arch anomalies was compared with the surgical results. Result: The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CTA and TTE for congenital aortic arch anomalies (including intracardiac and extracardiac structural abnormalities) were 92.2% and 85.5%, 99.4%, and 99.1%, 97.4% and 95.6%, 98.1% and 96.9%, and 97.2% and 95.2%, respectively. Regarding extracardiac structural malformations, the sensitivity of CTA was 100%, whereas that of TTE was 78.6% (P < 0.001). Regarding intracardiac structural malformations, the sensitivity of CTA was 84.5%, whereas that of TTE was 92.5% (P < 0.001). Regarding satisfaction with the images in aortic arch anomalies, surgeons noted that the CTA images were more useful for diagnosis and operation planning compared with TTE. Conclusion: Wide-detector revolution CT angiography combined with prospective ECG triggering can be routinely used to assess congenital aortic arch anomalies, providing adequate image quality and high diagnostic accuracy. However, limitations in the identification of intracardiac structural abnormalities are noted.
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Furoquinolone and its derivatives exhibit antimicrobial, anti-allergic, anti-inflammatory and anticancer properties. The present study investigated the anti-tumor activity of synthesized intermediates of furoquinolone in human promyelocytic leukemia HL-60 cells. The biological effects of the active compound ethyl 2-anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (compound 131) were examined in HL-60 cells. The following properties were analyzed: Cell survival, cell cycle profile, caspase-3 activity, Bax and Bcl-2 expression, the amount of intracellular Ca2+, the number of reactive oxygen species (ROS) and the mitochondrial membrane potential. Compound 131 (50% cytotoxic concentration, 23.5 µM) significantly reduced the proliferation of HL-60 cells and was revealed to induce apoptosis in HL-60 cells in a concentration-dependent manner. Moreover, this was associated with the activation of caspase-3, upregulation of Bax, an increase in intracellular Ca2+ and ROS production, and a decrease in mitochondrial membrane potential and Bcl-2 expression levels. Compound 131, a novel 4,5-dihydrofuran-3-carboxylate, induced apoptosis in HL-60 cells via the increase of intracellular Ca2+ and ROS to alter the mitochondrial membrane potential and the protein level of Bax and Bcl-2, as well as activating caspase-3. The results of the current study indicate that compound 131 may represent a promising compound for the development of anti-leukemia therapeutics.
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Photocatalytic water splitting has become a promising strategy for converting solar energy into clean and carbon-neutral solar fuels in a low-cost and environmentally benign way. Hydrogen gas is such a potential solar fuel/energy carrier. In a classical artificial photosynthetic system, a photosensitizer is generally associated with a co-catalyst to convert photogenerated charge into (a) chemical bond(s). In the present study, assemblies consisting of CdSe quantum dots that are coupled with one of two molecular complexes/catalysts, that is, [Fe2 S2 (CO)6 ] or [Fe3 Te2 (CO)9 ], using an interface-directed approach, have been tested as catalytic systems for hydrogen production in aqueous solution/organic solution. In the presence of ascorbic acid as a sacrificial electron donor and proton source, these assemblies exhibit enhanced activities for the rate of hydrogen production under visible light irradiation for 8â h in aqueous solution at pHâ 4.0 with up to 110â µmol of H2 per mg of assembly, almost 8.5â times that of pure CdSe quantum dots under the same conditions. Transient absorption and time-resolved photoluminescence spectroscopies have been used to investigate the charge carrier transfer dynamics in the quantum dot/iron carbonyl cluster assemblies. The spectroscopic results indicate that effective electron transfer from the molecular iron complex to the valence band of the excited CdSe quantum dots significantly inhibits the recombination of photogenerated charge carriers, boosting the photocatalytic activity for hydrogen generation; that is, the iron clusters function as effective intermediaries for electron transfer from the sacrificial electron donor to the valence band of the quantum dots.
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BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive inherited disorder caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut- enzymatic subtype, respectively); a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, or cblD-MMA); or deficiency of the enzyme methylmalonyl-CoA epimerase. The cblA type of MMA is very rare in China. This study aimed to describe the biochemical, clinical, and genetic characteristics of two siblings in a Chinese family, suspected of having the cblA-type of MMA. METHODS: The Chinese family of Han ethnicity of two siblings with the cblA-type of MMA, was enrolled. Target-exome sequencing was performed for a panel of MMA-related genes to detect causative mutations. The influence of an identified missense variant on the protein's structure and function was analysed using SIFT, PolyPhen-2, PROVEAN, and MutationTaster software. Moreover, homology modelling of the human wild-type and mutant proteins was performed using SWISSMODEL to evaluate the variant. RESULTS: The proband was identified via newborn screening (NBS); whereas, her elder brother, who had not undergone expanded NBS, was diagnosed later through genetic family screening. The younger sibling exhibited abnormal biochemical manifestations, and the clinical performance was relatively good after treatment, while the older brother had a mild biochemical and clinical phenotype, mainly featuring poor academic performance. A novel, homozygous missense c.365T>C variant in exon 2 of their MMAA genes was identified using next-generation sequencing and validated by Sanger sequencing. Several different types of bioinformatics software predicted that the novel variant c.365T>C (p.L122P) was deleterious. Furthermore, three-dimensional crystal structure analysis revealed that replacement of Leu122 with Pro122 led to the loss of two intramolecular hydrogen bonds between the residue at position 122 and Leu188 and Ala119, resulting in instability of the MMAA protein structure. CONCLUSIONS: The two siblings suspected of having the cblA-type of MMA showed mild phenotypes during follow-up, and a novel, homozygous missense variant in their MMAA genes was identified. We believe that the clinical features of the two siblings were associated with the MMAA c.365T>C variant; however, further functional studies are warranted to confirm the variant's pathogenicity.
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Erros Inatos do Metabolismo dos Aminoácidos/genética , Povo Asiático/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , Sequência de Aminoácidos , Criança , Feminino , Homozigoto , Humanos , Lactente , Masculino , Mutação de Sentido Incorreto/genética , Fenótipo , IrmãosRESUMO
OBJECTIVE: To investigate the mutations of SLC22A5 gene in patients with systemic primary carnitine deficiency (CDSP). METHODS: High liquid chromatography tandem mass spectrometry (HPLC/MS/MS) was applied to screen congenital genetic metabolic disease and eight patients with CDSP were diagnosed among 77 511 samples. The SLC22A5 gene mutation was detected using massarray technology and sanger sequencing. Using SIFT and PolyPhen-2 to predict the function of protein for novel variations. RESULTS: Total detection rate of gene mutation is 100% in the eight patients with CDSP. Seven patients had compound heterozygous mutations and one patient had homozygous mutations. Six different mutations were identified, including one nonsense mutation [c.760C>T(p.R254X)] and five missense mutations[c.51C>G(p.F17L), c.250T>A(p.Y84N), c.1195C>T(p.R399W), c.1196G>A(p.R399Q), c.1400C>G(p.S467C)]. The c.250T>A(p.Y84N) was a novel variation, the novel variation was predicted to have affected protein structure and function. The c.760C>T (p.R254X)was the most frequently seen mutation, which was followed by the c.1400C>G(p.S467C). CONCLUSION: This study confirmed the diagnosis of eight patients with CDSP on the gene level. Six mutations were found in the SLC22A5 gene, including one novel mutation which expanded the mutational spectrum of the SLC22A5 gene.
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Cardiomiopatias/genética , Carnitina/deficiência , Hiperamonemia/genética , Doenças Musculares/genética , Mutação , Proteínas de Transporte de Cátions Orgânicos/genética , Adulto , Sequência de Aminoácidos , Sequência de Bases , Cardiomiopatias/diagnóstico , Cardiomiopatias/metabolismo , Carnitina/genética , Carnitina/metabolismo , Análise Mutacional de DNA/métodos , Feminino , Frequência do Gene , Genótipo , Humanos , Hiperamonemia/diagnóstico , Hiperamonemia/metabolismo , Recém-Nascido , Masculino , Doenças Musculares/diagnóstico , Doenças Musculares/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Homologia de Sequência de Aminoácidos , Membro 5 da Família 22 de Carreadores de Soluto , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Integrin-linked kinase (ILK) mediates signal transduction between cells and the extracellular matrix, regulating cell proliferation, migration, angiogenesis, and apoptosis. However, its roles in the formation of hypertrophic scars are not yet clear. In this study, we found that ILK was predominantly expressed on the microvascular endothelial cells and the epidermal basal cells of human hypertrophic scars. The proliferation, migration and angiogenesis of primary human scar microvascular endothelial cells (HSMECs) were significantly inhibited after ILK was silenced. The ILK inhibitor QLT0267 had the same effect of impeding angiogenesis in vitro by blocking ILK activity. Both siRNA and QLT0267 markedly decreased the expression of vascular endothelial growth factor, but not its receptors, such as human vascular endothelial cell growth factor receptor 1 or kinase insert domain-containing receptor. We also showed that the expression of ILK was enhanced by inducing mild hypoxia with CoCl2, but it was suppressed under serious hypoxia. Thus, ILK regulates HSMEC proliferation and angiogenesis and participates in the formation of hypertrophic scars, in which mild hypoxia may be the mechanism of action.
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Cicatriz , Hipóxia , Neovascularização Patológica , Proteínas Serina-Treonina Quinases/fisiologia , Fator A de Crescimento do Endotélio Vascular , HumanosRESUMO
The interactions between fibroblasts and the extracellular matrix in wound contraction are mainly mediated via integrin signaling. Integrin-linked kinase (ILK) is a key mediator in integrin signal transduction. We investigated the role of ILK in cutaneous wound contraction. We found that ILK was involved in cutaneous wound healing in rats, and ILK and PI3K/AKT inhibitors inhibited wound contraction and re-epithelialization, consequently delaying wound healing in vivo. Further, using in vitro studies, we demonstrated that ILK and PI3K/AKT inhibitors suppressed the contraction of fibroblast-populated collagen lattices, inhibited fibroblast migration, and interrupted the effect of TGF-ß1 on promoting alpha smooth muscle actin (α-SMA) expression in fibroblasts. When ILK expression was directly blocked by ILK small interfering RNA transfection, the migration and α-SMA expression of normal dermal fibroblasts were significantly suppressed as well. The data suggest that the ILK-PI3K/AKT signaling pathway mediates cutaneous wound contraction by regulating fibroblast migration and differentiation to myofibroblasts.
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Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pele/lesões , Pele/metabolismo , Cicatrização/fisiologia , Actinas/metabolismo , Animais , Compostos Azo/farmacologia , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Cromonas/farmacologia , Colágeno/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Morfolinas/farmacologia , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Pirazóis/farmacologia , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Pele/patologia , Fator de Crescimento Transformador beta1/metabolismo , Cicatrização/efeitos dos fármacos , Cicatrização/genéticaRESUMO
OBJECTIVE: To investigate the role of integrin-linked kinase (ILK) signaling pathway in the skin lesions and wound healing in diabetic rats. METHODS: Thirty-six SD rats were divided into diabetic wound group (D) and non-diabetic wound group (N) according to the random number table, with 18 rats in each group. 10 g/L streptozocin (60 mg/kg) was intraperitoneally injected in rats in group D, while the rats in group N were given same quantity of sodium citrate buffer. Two weeks after successful reproduction of diabetic model of rats in group D, two full-thickness skin of an area of 2 cm × 2 cm was resected on both sides of back of rats in the two groups. Wounds of three rats of each group were photographed and examined on post injury day (PID) 1, 3, 7, 10, 14, and 21, and the wound healing rates were calculated. The non-injured skin and wound tissue (central part) on back of three rats of the rest 15 rats in the two groups were harvested on PID 3, 7, 10, 14, and 21, respectively. Morphology of the non-injured skin tissue was observed with HE staining, and the thickness of full-thickness skin and epidermis were measured. The mRNA expression levels of ILK, protein kinase B (Akt), and glycogen synthase kinase-3ß (GSK-3ß) in non-injured skin tissue were determined with real-time fluorescent quantitative RT-PCR. The protein expression levels of ILK, Akt, phosphorylated Akt, GSK-3ß, and phosphorylated GSK-3ß in non-injured skin tissue, and ILK, phosphorylated Akt in wound tissue were assessed with Western blotting. Data were processed with two independent-sample t test, one-way analysis of variance, SNK test and analysis of variance of factorial design. RESULTS: (1) After injury, the wound scabs of rats in group N were dry, and red granulation tissue with no excretion were seen when the scabs fell off, and the wound healed fast. After injury, excretion under the wound scabs of rats in group D was seen, and the scabs easily fell off with exposure of pink granulation tissue with much excretion, and the wounds healed slowly. Except for PID 3, the wound healing rate of rats in group D was significantly lower than that in group N on other PIDs (with t values from 3.858 to 13.738, P<0.05 or P<0.01). (2) On PID 3, the hair follicles and blood vessels in the non-injured skin tissue of rats in group N were rich, and the epidermis was composed of stratified cells in form of basal cells and keratinocyte, and the hair follicles and blood vessels in the non-injured skin tissue of rats in group D were scarce, and the epidermis was nearly composed of one-layer of cells. The thickness of full-thickness skin and epidermis of non-injured skin tissue of rats in group N was similar from PID 3 to 21, and the thickness of full-thickness skin and epidermis of non-injured skin tissue of rats in group D on PID 3 was respectively (1 074 ± 66) and (15.1 ± 3.8) µm, and they gradually thinned out to (785 ± 122) and (9.7 ± 2.1) µm on PID 21, respectively. The thickness of full-thickness skin and epidermis of non-injured skin tissue of rats in group N were significantly thicker than those in group D on each PID (with t values from 4.620 to 23.549, P values below 0.001). (3) From PID 3 to 21, the mRNA expression levels of ILK and Akt in non-injured skin tissue of rats in group D were significantly lower than those in group N (with t values respectively 4.779 and 3.440, P values below 0.05), the mRNA expression levels of GSK-3ß in non-injured skin tissue of rats were similar in two groups (t=0.363, P>0.05). (4) From PID 3 to 21, the protein expression levels of ILK, Akt and phosphorylated Akt in non-injured skin tissue of rats in group D were significantly lower than those in group N (with t values from 2.630 to 6.209, P<0.05 or P<0.01); the protein expression levels of GSK-3ß in non-injured skin tissue of rats in two groups were similar (t=0.652, P>0.05); the protein expression level of phosphorylated GSK-3ß in non-injured skin tissue of rats in group D was significantly higher than that in group N (t=4.131, P<0.001). The protein expression levels of ILK in wound tissue of rats in two groups were similar on each PID (with t values from 0.381 to 2.440, P values above 0.05). Except for PID 3, the protein expression levels of phosphorylated Akt in wound tissue of rats in group N were significantly higher than that in group D on other PIDs (with t values from 4.091 to 20.555, P<0.05 or P<0.01). From PID 3 to 21, the protein expression levels of ILK in wound tissue and non-injured skin tissue of rats in group N were similar (F=2.522, P>0.05), and the protein expression level of phosphorylated Akt in wound tissue was significantly higher than that in non-injured skin tissue (F=117.329, P<0.001); the protein expression levels of ILK in wound tissue and non-injured skin tissue of rats in group D were similar (F=1.337, P>0.05), and the protein expression level of phosphorylated Akt in wound tissue was significantly higher than that in non-injured skin tissue (F=184.120, P<0.001). CONCLUSIONS: The skin lesion of diabetic rats may be related to the declined expression levels of ILK, Akt and phosphorylated Akt in the ILK signaling pathway. The refractory healing of wound in diabetic rats may be related to the declined expression level of phosphorylated Akt.
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Diabetes Mellitus Experimental/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Pele/lesões , Cicatrização , Animais , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Objective: To investigate the effects of retinoic acid (RA) on the proliferation and apoptosis of mesenchyme and epithelium at the key stages of palatal development, and to determine the embryonic alterations associated with cleft palate. Methods: 100 pregnant C57 females (E12) were equally divided into two groups. The experimental group was administered RA once (70 mg/kg) while the control group was administered corn oil only, and the heads of the embryos at E13.5-17.5 were collected and processed to paraffin. Sections were stained with hematoxylin and eosin for the morphological assessment of anterior,posterior, left and right palate, and BrdU and TUNEL assays for the detection of proliferation and survival of palatal mesenchyme and epithelium. Results: Simple treatment of RA at 70 mg/kg caused an incidence of 100ï¼ cleft palate. During E13.5-15.5,cell proliferation was significantly promoted on the anterior palatal mesenchyme in the RA group, while no difference for the posterior palatal mesenchyme. Besides, the cell proliferation on anterior and posterior epithelium was comparable between the control and RA group. Less apoptotic cells were observed on epithelium during El3.5-14.5 in the RA group. Conclusions: RA induces excessive cell proliferation of palatal mesenchyme, causing abnormal vertical palatal growth and failure of palatal shelves contact and fusion, which finally lead to cleft palate. RA also increases epithelium apoptosis.
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Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fissura Palatina/induzido quimicamente , Ceratolíticos/farmacologia , Palato/embriologia , Tretinoína/farmacologia , Animais , Epitélio , Feminino , Mesoderma , Palato/efeitos dos fármacos , GravidezRESUMO
OBJECTIVE: To explore the special significances in advantages of using anti-inflammatory drugs, such as amelioration of growing conditions and the promotion of cell growth. METHODS: Utilizing anti-adhesive effects of synthetic E-selectins, we observed the changes of inflammatory cytokines (TNF-α, IL-1ß) contented in brain tissues and rat serums in rats hind cerebral ischemia-reperfusion models. Both growth and expression of endogenetic/exogenous neurological stem cells were detected after ameliorated local microenvironment. RESULTS: The contents of TNF-α and IL-1ß were decreased in brain tissues and rat serums after applying synthetic E-selectins. Expression of exogenous neurological stem cells was enhanced. Animal neurological functions improved. CONCLUSION: Anti-inflammatory therapy in early stage could enhance proliferation of stem cells so that it has vital significations in treating cerebrovascular diseases.
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Anti-Inflamatórios/farmacologia , Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Selectina E/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Nicho de Células-Tronco , Animais , Anti-Inflamatórios/síntese química , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Isquemia Encefálica/sangue , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Citoproteção , Modelos Animais de Doenças , Feminino , Interleucina-1beta/sangue , Masculino , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Fármacos Neuroprotetores/síntese química , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: To study the role of integrin-linked kinase (ILK) on the proliferation and differentiation of human fibroblast in hypertrophic scar and its effect on the scar formation. METHODS: The human scar fibroblasts were isolated and cultured in vitro. The cells were divided into 4 groups. (1) control group: only contains DMEM; (2) jetPRIME group: DMEM with 200 microl jetPRIME buffer and 4 microl jetPRIME; (3) ILK siRNA group: DMEM and ILK siRNA; (4) ILK cDNA group: DMEM and ILK cDNA. The cell proliferation was detected by XTT assay and the mRNA and protein expressions of ILK and alpha-SMA were detected by Real-time qPCR and Western blot. RESULTS: (1) XTT results showed that the cellular proliferation level after 48 h in four groups were 0.820 +/- 0.065, 0.873 +/- 0.041, 0.554 +/- 0.013 and 1.296 +/- 0.094, respectively. The cellular proliferation curve showed that the cellular proliferation level was very flat in ILK siRNA group while the cellular proliferation level gradually increased from 12 h. 48 h after transfection, the cellular proliferation level in ILK siRNA group was significant lower than those in other groups (P value were 0.021, 0.034, 0), while the cellular proliferation level in ILK cDNA group was the highest among all 4 groups (P value were 0.017, 0.009, 0). (2) The Real-time qPCR showed that the expressions of ILK mRNA and alpha-SMA mRNA were 0.693 +/- 0.412 and 0.422 +/- 0.037 in control group, were 0.621 +/- 0.183 and 0.388 +/- 0.005 in jetPRIME group, were 0.052 +/- 0.019 and 0.073 +/- 0.023 in ILK siRNA group, were 240.193 +/- 35.170 and 138.056 +/- 24.060 in ILK cDNA group. The expressions of ILK mRNA and alpha-SMA mRNA in ILK siRNA group were significantly lower than those in other three groups (P < 0.05). And the expressions of ILK mRNA and alpha-SMA mRNA in ILK cDNA group were significantly higher than those in other three groups (P < 0.05). (3) The Western blot also showed that the expression of ILK and alpha-SMA proteins were decreased in ILK siRNA group and increased in ILK cDNA group. CONCLUSION: ILK may promote the proliferation and differentiation of human scar fibroblast. It may play an important role in scar formation and contracture.
Assuntos
Cicatriz Hipertrófica/metabolismo , Fibroblastos/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/farmacologia , Actinas/metabolismo , Adolescente , Adulto , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Transfecção , Adulto JovemRESUMO
This article reports the treatment of a patient suffered from acute radiation burn covering 41% TBSA, with deep partial-thickness and full-thickness injury, produced by exposure to a large-scale industrial electron accelerator. An open wound began to appear and enlarged gradually 10 weeks after the exposure. Serious wound infection with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, pneumonia, respiratory failure, systemic inflammatory response syndrome, nephropathy and hypoproteinemia developed successively since 3 weeks after the wound formation. Skin grafts failed to survive, resulting in enlargement of the wound. After being treated with proper measures, including parenteral nutrition, respiratory support with a ventilator, appropriate antibiotics, steroid administration for nephropathy, deep debridement for wounds followed by skin grafting, the patient was cured and discharged after undergoing 15 operations in 500 days. The clinical condition of an extensive acute radiation burn is complicated. We should pay close attention to the changes in functions of organs, and strengthen the therapeutic strategies to support the function of organs to reduce the incidence of systemic complications. The control of the infection and the timely and effective repair of the wound are still the key points of the treatment of an extensive local radiation injury.
Assuntos
Queimaduras/terapia , Lesões por Radiação/terapia , Doença Aguda , Adulto , Queimaduras/complicações , Queimaduras/microbiologia , Humanos , Masculino , Lesões por Radiação/complicações , Infecção dos Ferimentos/terapiaRESUMO
A patient sustained acute third-degree radiation burns over 41% of his body surface. The burns were due to occupational injury caused by an electron accelerator. Most of his wounds appeared and spread gradually during the 10th week after the radiation burn. Subsequently, severe wound infection with methicillin-resistant Staphylococcus aureus, severe pneumonia, respiratory failure, systemic inflammatory response syndrome, nephropathy, and hypoproteinemia had developed 3 months after the radiation injury. Most of the skin grafts could neither survive nor spread on the fresh wound after removing the necrotic tissue. This phenomenon resulted in many more wounds after operations, increasing the risk of wound infection. Parenteral nutrition, respiratory support with a ventilator, antibiotics for methicillin-resistant Staphylococcus aureus, steroid therapeutics for nephropathy, deeper debridement for wounds, and skin grafting were applied for treatment of this patient. The patient recovered gradually and was discharged from the hospital in good condition after 18 months. The authors suggest that deeper excision of necrotic tissue and skin grafting as well as appropriate antibiotics are principal measures to counteract systemic inflammatory response syndrome. Sufficient albumen by vein and steroid should be administered for treatment against nephropathy and for control of infection. Functions of organs should be carefully monitored to fine-tune the therapeutic programs and to minimize complications of organs.