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BACKGROUND: The repair of facial skin and soft tissue defects remains a clinical challenge. The author introduced a novel "table tennis racquet" random skin flap for wound repair after facial skin cancer excision and discussed its survival mechanisms. METHODS: A lateral mandibular neck skin flap shaped like a table tennis racquet with no well-known blood vessels at the narrow pedicle was designed in 31 cases to repair tissue defects. Among them, there were 8 cases of skin carcinoma in the frontotemporal area and 23 cases of skin carcinoma in the cheek. The flap area was 8.0 × 7.0 cm at maximum and 3.0 × 2.5 cm at minimum, with a pedicle width of 1.0-2.0 cm and a pedicle length of 2.0-6.0 cm. RESULTS: All 31 "table tennis racquet" random skin flaps survived, although there were 3 cases with delayed healing of distal flap bruising. All of them had an ideal local shape after repair with a concealed donor area and inconspicuous scars. CONCLUSIONS: This flap has a "table tennis racquet" shape with a pedicle without well-known blood vessels and has a length-to-width ratio that exceeds that of conventional random flaps, making it unconventional. Because of its long and narrow pedicle, it not only has a large rotation and coverage area but also can be designed away from the defect area, avoiding the defect of no donor tissue being localized near the defect. Overall, this approach is an ideal option for repairing tissue defects after enlarged excision of facial skin carcinoma.
Assuntos
Neoplasias Faciais , Procedimentos de Cirurgia Plástica , Neoplasias Cutâneas , Retalhos Cirúrgicos , Humanos , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Faciais/cirurgia , Idoso , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Resultado do Tratamento , Transplante de Pele/métodos , Adulto , Cicatrização/fisiologia , Idoso de 80 Anos ou mais , Sobrevivência de EnxertoRESUMO
BACKGROUND: Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases and is the leading cause of pain and disability in the aged population. However, the underlying biological mechanism has not been fully understood. This study aims to reveal the causal effect of circulation metabolites on OA susceptibility. METHODS: A two-sample Mendelian Randomization (MR) analysis was performed to estimate the causality of GDMs on OA. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, whereas 8 different OA phenotypes, including any-site OA (All OA), knee and/or hip OA (knee/hip OA), knee OA, hip OA, spine OA, finger and/or thumb OA (hand OA), finger OA, thumb OA, were set the outcomes. Inverse-variance weighted (IVW) was used for calculating causal estimates. Methods including weight mode, weight median, MR-egger, and MR-PRESSO were used for the sensitive analysis. Furthermore, metabolic pathway analysis was performed via the web-based Metaconflict 4.0. All statistical analyses were performed in R software. RESULTS: In this MR analysis, a total of 235 causative associations between metabolites and different OA phenotypes were observed. After false discovery rate (FDR) correction and sensitive analysis, 9 robust causative associations between 7 metabolites (e.g., arginine, kynurenine, and isovalerylcarnitine) and 5 OA phenotypes were finally identified. Additionally, eleven significant metabolic pathways in 4 OA phenotypes were identified by metabolic pathway analysis. CONCLUSION: The finding of our study suggested that identified metabolites and metabolic pathways can be considered useful circulating metabolic biomarkers for OA screening and prevention in clinical practice, and can also serve as candidate molecules for future mechanism exploration and drug target selection.
Assuntos
Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteoartrite do Joelho/genética , Redes e Vias Metabólicas/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Lumbar spinal stenosis (LSS), which can lead to irreversible neurologic damage and functional disability, is characterized by hypertrophy and fibrosis in the ligamentum flavum (LF). However, the underlying mechanism is still unclear. In the current study, the effect of Smurf1, a kind of E3 ubiquitin ligase, in promoting the fibrosis and oxidative stress of LF was investigated, and its underlying mechanism was explored. The expression of oxidative stress and fibrosis-related markers was assessed in the tissue of lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). Next, the expression of the top 10 E3 ubiquitin ligases, obtained from Gene Expression Omnibus (GEO) dataset GSE113212, was assessed in LDH and LSS, and confirmed that Smurf1 expression was markedly upregulated in the LSS group. Furthermore, Smurf1 overexpression promotes the fibrosis and oxidative stress of LF cells. Subsequently, NRF2, an important transcription factor for oxidative stress and fibrosis, was predicted to be a target of Smurf1. Mechanistically, Smurf1 directly interacts with Nrf2 and accelerates Nrf2 ubiquitination and degradation. In conclusion, the current study suggests that Smurf1 facilitated the fibrosis and oxidative stress of LF and induced the development of LSS by promoting Nrf2 ubiquitination and degradation.
Assuntos
Ligamento Amarelo , Estenose Espinal , Humanos , Estenose Espinal/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ligamento Amarelo/metabolismo , Ligamento Amarelo/patologia , Fibrose , Ubiquitinação , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Vértebras Lombares/metabolismo , Hipertrofia/metabolismo , Hipertrofia/patologia , Estresse OxidativoRESUMO
This study aimed to identify the target genes of IGFBP3ï¼insulin growth factor binding proteinï¼protein and to investigate its target genes effects on the proliferation and differentiation of Hu sheep skeletal muscle cells. IGFBP3 was an RNA-binding protein that regulates mRNA stability. Previous studies have reported that IGFBP3 promotes the proliferation of Hu sheep skeletal muscle cells and inhibits differentiation, but the downstream genes that bind to it have not been reported yet. We predicted the target genes of IGFBP3 through RNAct and sequencing data, and verified by qPCR and RIPï¼RNA Immunoprecipitationï¼experiments, and demonstrated GNAI2ï¼G protein subunit alpha i2ï¼as one of the target gene of IGFBP3. After interference with siRNA, we carried out qPCR, CCK8, EdU, and immunofluorescence experiments, and found that GNAI2 can promote the proliferation and inhibit differentiation of Hu sheep skeletal muscle cells. This study revealed the effects of GNAI2 and provided one of the regulatory mechanisms of IGFBP3 protein underlying sheep muscle development.
Assuntos
Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Fibras Musculares Esqueléticas , Animais , Ovinos/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fibras Musculares Esqueléticas/metabolismo , RNA Interferente Pequeno , Diferenciação Celular , Proliferação de Células/genética , Músculo Esquelético/metabolismoRESUMO
Hippocampal sclerosis (HS) is the most common surgical pathology associated with temporal lobe epilepsy (TLE). However, the cause of TLE with or without HS remains unknown. Our current study aimed to illustrate the essential molecular mechanism that is potentially involved in the pathogenesis of TLE-HS and to shed light on the transcriptional changes associated with hippocampal sclerosis. Compared to no-HS group, 341 mRNA transcripts and 131 circRNA transcripts were differentially expressed in ILAE type 1 group. The raw sequencing data have been deposited into sequence-read archive (SRA) database under accession number PRJNA699348.Gene Ontology analysis demonstrated that the dysregulated genes were associated with the biological processes of vesicle-mediated transport. Enrichment analysis demonstrated that dysregulated genes were involved mainly in the MAPK signal pathway. Subsequently, A total of 441 known or predicted interactions were formed among DEGs, and the most important module was detected in the PPI network using the MCODE plug-in. There were mainly four functional modules enriched: ER to Golgi transport vesicle membrane, Basal transcription factors, GABA-gated chloride ion channel activity, CENP-A containing nucleosome assembly. A circRNA-mRNA co-expression network was constructed including 5 circRNAs(hsa_circ_0025349, hsa_circ_0002405, hsa_circ_0004805, hsa_circ_0032254, and hsa_circ_0032875) and three mRNAs (FYN, SELENBP1, and GRIPAP1) based on the normalized mRNA signal intensities. This is the first to report the circRNAs and mRNAs expression profile of surgically resected hippocampal tissues from TLE patients of ILAE-1 and no-HS, and these results may provide new insight into the transcriptional changes associated with this pathology.
Assuntos
Epilepsia do Lobo Temporal , MicroRNAs , Proteína Centromérica A/genética , Proteína Centromérica A/metabolismo , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/patologia , Gliose/patologia , Hipocampo/metabolismo , Humanos , MicroRNAs/genética , Nucleossomos , RNA Circular/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esclerose/genética , Esclerose/patologia , Fatores de Transcrição/genética , Ácido gama-AminobutíricoRESUMO
Pear fruits have been reported to contain abundant bioactive compounds and exhibit antidiabetic activity. In this study, Pingguoli pear (Pyrus pyrifolia cv.'Pingguoli') fermentation broth was sequentially extracted by five solvents with increasing polarity (petroleum ether, chloroform, ethyl acetate, n-butanol, and water) to evaluate its antioxidant and hypothermic activities, and then the main compounds of the fraction with the highest activity were assessed, which might be responsible for such activities. The results showed that the ethyl acetate fraction (EAF) exhibited the highest antioxidant activity according to DPPH (IC50 = 0.238 mg/mL), ABTS (IC50 = 0.293 mg/mL), and FRAP (IC50 = 0.193 mg/mL) assays. The in vitro hypoglycemic activity assay showed that EAF exhibited the strongest inhibitory effect, with IC50 values of 0.34 and 0.95 mg/mL for α-amylase and α-glucosidase, respectively. The glucose consumption in HepG2 cells treated with EAF was significantly increased to 252%, compare with control group. Liquid chromatography-mass spectrometry analysis implied that the main compounds, 3'-C-glucosylisoliquiritigenin, robustside D, caffeic acid, and chlorogenic acid may be potential candidates for the antioxidant and hypoglycemic activities of the EAF. This study suggested that EAF of Pingguoli pear fermentation broth could be utilized for development of potential functional food and antidiabetic agents.
Assuntos
Antioxidantes , Pyrus , 1-Butanol , Acetatos , Antioxidantes/química , Antioxidantes/farmacologia , Clorofórmio , Ácido Clorogênico , Fermentação , Glucose , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Solventes , Água , alfa-Amilases , alfa-GlucosidasesRESUMO
Intervertebral disc degeneration (IDD) is the main cause of low back pain and the mechanism of which is far from fully revealed. Although inflammation directed nucleus pulposus (NP) extracellular matrix metabolism dysregulation is known to be the main cause of the degeneration process, few is known about the protective factors. Using high-throughput label-free proteomics, we found that inflammation-related autocrine factor Chitinase-3-like protein 1 (CHI3L1, or YKL-40) is highly expressed in the NP cells during degeneration. Immunohistochemical analysis show that the expression of CHI3L1 is NP tissue specific, and increase significantly during degeneration. Overexpression of CHI3L1 significantly decrease the catabolism, and increase the anabolism of extracellular matrix. Knockdown of CHI3L1 using siRNAs show the opposite results, which imply that the protective role of CHI3L1 in IDD. Using high-throughput RNA sequencing and functional analyses, we find that AKT3 expression and its phosphorylation is mainly regulated by CHI3L1. And lastly, the mechanism of which is also validated using human and mouse degenerated NP tissues. In summary, our findings show that the inflammation-related autocrine factor CHI3L1 is NP specific, and it protects IDD by promoting the AKT3 signaling, which may serve as a potential therapeutic target in intervertebral disc degeneration.
Assuntos
Proteína 1 Semelhante à Quitinase-3/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Western Blotting , Células Cultivadas , Proteína 1 Semelhante à Quitinase-3/genética , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Degeneração do Disco Intervertebral/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/genética , Fosforilação/fisiologia , Proteômica , Proteínas Proto-Oncogênicas c-akt/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
Epilepsy represents a hazardous neurological disorder, underpinned by a pathophysiological process that is yet to be fully understood. Here, we aimed to elucidate the effect of methyl-CpG-binding domain protein 3 (MBD3) on hippocampal neuronal damage in epileptic mice by targeting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. The expression of MBD3 was determined by Western blot in a hippocampal neuronal culture (HNC) epileptic model established using the low Mg2+ECF culture method. The interaction between MBD3 and DNA methyltransferase 1 (DNMT1) was determined via co-immunoprecipitation and mass spectrometry analysis. Bisulfite modification and sequencing was performed to evaluate the degree of methylation of triggering receptor expressed on myeloid cells 2 (TREM2). The viability and apoptosis of hippocampal neurons were detected by CCK-8 and TUNEL assays, respectively. Finally, the effect of MBD3 was verified in vivo. MBD3 was highly expressed in the HNC model of epilepsy, with its interaction with DNMT1 found to promote the hypermethylation of TREM2 at site cg25748868. Additionally, decreased TREM2 and inhibited PI3K/Akt pathway was observed in the HNC epileptic model. Simultaneous inhibition of MBD3 and DNMT1 decreased the methylation level at cg25748868, up-regulated TREM2 expression, and activated the PI3K/Akt pathway, thereby arresting neuronal damage. Inhibition of MBD3 reduced the level of epileptic seizures, down-regulated cg25748868 methylation, activated TREM2-mediated signaling pathways, and alleviated hippocampal neuronal damage in the acute seizure mouse models. The present study unveiled that MBD3 and DNMT1 synergistically enhanced hypermethylation of cg25748868 in TREM2, and promoted the onset of epilepsy via inhibition of the PI3K/Akt pathway.
Assuntos
DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Proteínas de Ligação a DNA/metabolismo , Epilepsia/fisiopatologia , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Convulsões/fisiopatologia , Fatores de Transcrição/metabolismo , Animais , Apoptose/fisiologia , Sobrevivência Celular/fisiologia , Epilepsia/etiologia , Epilepsia/patologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Glicoproteínas de Membrana/química , Metilação , Camundongos Endogâmicos ICR , Neurônios/metabolismo , Neurônios/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Imunológicos/química , Convulsões/etiologia , Convulsões/patologia , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: Many types of lasers have been used to treat café-au-lait macules (CALMs) since the introduction of the selective photothermolysis theory. However, the efficacy and safety of picosecond lasers, compared with those of nanosecond lasers, have not been researched. To compare the efficacy and safety of 755 nm picosecond laser (PS-755 nm), Q-switched (QS) Alexandrite 755 nm nanosecond laser (QS-755 nm), and QS Nd:YAG 532 nm nanosecond laser (QS-532 nm) for treating CALMs. STUDY DESIGN/MATERIALS AND METHODS: Forty-one patients received several treatments at 3-month intervals. Lesions were divided into two or three approximately equal parts, which were randomly treated with PS-755 nm, QS-755 nm, and QS-532 nm. The safety and efficacy of three lasers were determined based on blinded visual assessments and self-reports of patients three months after the comparative trial. RESULTS: Visual assessment 3 months after the comparative trial revealed that there was no statistically significant difference among the sites treated by QS-755 nm (2.84 ± 1.11), QS-532 nm (2.63 ± 1.06), and PS-755 nm (2.74 ± 1.05) lasers. Five (26.32%) of 19 patients showed lesion recurrence. Adverse effects included acneiform miliaris, hypopigmentation, and hyperpigmentation, which were resolved within 12 months. Five (26.32%) of 19 patients who showed lesion recurrence 1-5 months after laser treatment had lightened or cleared at least 50% of the lesion. 46.67% of patients were satisfied or very satisfied with the outcome of the overall treatment. CONCLUSIONS: PS-755 nm, QS-755 nm, and QS-532 nm laser treatments were equally effective in treating and improving CALMs. PS-755 nm caused fewer adverse effects. Individuals can react differently to different types of lasers. Patch tests should be conducted before the treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
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Hiperpigmentação , Lasers de Estado Sólido , Terapia com Luz de Baixa Intensidade , Manchas Café com Leite , Humanos , Lasers de Estado Sólido/uso terapêutico , Recidiva , Resultado do TratamentoRESUMO
LARP4A belongs to the ancient RNA-binding protein superfamily of La-related proteins (LARPs). In humans, it acts mainly by stabilizing mRNAs, enhancing translation and controlling polyA lengths of heterologous mRNAs. These activities are known to implicate its association with mRNA, protein partners and translating ribosomes, albeit molecular details are missing. Here, we characterize the direct interaction between LARP4A, oligoA RNA and the MLLE domain of the PolyA-binding protein (PABP). Our study shows that LARP4A-oligoA association entails novel RNA recognition features involving the N-terminal region of the protein that exists in a semi-disordered state and lacks any recognizable RNA-binding motif. Against expectations, we show that the La module, the conserved RNA-binding unit across LARPs, is not the principal determinant for oligoA interaction, only contributing to binding to a limited degree. Furthermore, the variant PABP-interacting motif 2 (PAM2w) featured in the N-terminal region of LARP4A was found to be important for both RNA and PABP recognition, revealing a new role for this protein-protein binding motif. Our analysis demonstrates the mutual exclusive nature of the PAM2w-mediated interactions, thereby unveiling a tantalizing interplay between LARP4A, polyA and PABP.
Assuntos
Autoantígenos/química , Poli A/química , Proteínas de Ligação a Poli(A)/química , RNA Mensageiro/química , Proteínas de Ligação a RNA/química , Ribonucleoproteínas/química , Motivos de Aminoácidos , Autoantígenos/genética , Autoantígenos/metabolismo , Sítios de Ligação , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Cinética , Modelos Moleculares , Poli A/genética , Poli A/metabolismo , Proteínas de Ligação a Poli(A)/genética , Proteínas de Ligação a Poli(A)/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Especificidade por Substrato , Termodinâmica , Antígeno SS-BRESUMO
A pyrimidine moiety exhibiting a wide range of pharmacological activities has been employed in the design of privileged structures in medicinal chemistry. To prepare libraries of novel heterocyclic compounds with potential biological activities, a series of novel 2-(pyridin-2-yl) pyrimidine derivatives were designed, synthesized and their biological activities were evaluated against immortalized rat hepatic stellate cells (HSC-T6). Fourteen compounds were found to present better anti-fibrotic activities than Pirfenidone and Bipy55'DC. Among them, compounds ethyl 6-(5-(p-tolylcarbamoyl)pyrimidin-2-yl)nicotinate (12m) and ethyl 6-(5-((3,4-difluorophenyl)carbamoyl)pyrimidin-2-yl)nicotinate (12q) show the best activities with IC50 values of 45.69 µM and 45.81 µM, respectively. Furthermore, the study of anti-fibrosis activity was evaluated by Picro-Sirius red staining, hydroxyproline assay and ELISA detection of Collagen type I alpha 1 (COL1A1) protein expression. Our study showed that compounds 12m and 12q effectively inhibited the expression of collagen, and the content of hydroxyproline in cell culture medium in vitro, indicating that compounds 12m and 12q might be developed the novel anti-fibrotic drugs.
Assuntos
Colágeno Tipo I/metabolismo , Fibrose/tratamento farmacológico , Células Estreladas do Fígado/efeitos dos fármacos , Prolil Hidroxilases/química , Pirimidinas/química , Animais , Linhagem Celular Tumoral , Proliferação de Células , Cadeia alfa 1 do Colágeno Tipo I , Ensaio de Imunoadsorção Enzimática , Concentração Inibidora 50 , RatosRESUMO
BACKGROUND: Congenital melanocytic nevi (CMN) that occur on the eyelid and periorbital region cause cosmetic disfiguring. Laser treatment has aroused interest as an alternative treatment method, and resurfacing lasers have shown promising results. OBJECTIVE: This study aimed to evaluate the efficacy and safety of carbon dioxide laser and erbium:yttrium aluminum garnet laser to treat CMN of the eyelid and periorbital region. METHODS AND MATERIALS: Twenty patients with CMN were included in this study and were treated with either the CO2 or erbium:yttrium aluminum garnet laser. Clinical efficacy outcomes were evaluated by visual assessment and L*a*b* color space evaluation at least 6 months after treatment. RESULTS: The average (SD) visual evaluation improvement, assessed on a 5-point scale, was 2.8 (1.27). The mean (SD) values of the relative L* improvement rate and blanching rate of the CMN lesion were 32.0% (47.9%) and 34.1% (36.2%), respectively. Spearman rank correlation coefficient between the objective and subjective evaluations was significant (P < 0.001). Three cases developed partial hypopigmentation. No patient developed hypertrophic scars. CONCLUSION: The outcomes after laser treatment were variable, although half of the patients achieved greater than 50% clearance. It provides an alternative to surgical excision for the removal of CMN in the difficult regions. Surgery excision is inevitable for some patients.
Assuntos
Pálpebras , Face , Terapia a Laser/instrumentação , Terapia a Laser/métodos , Nevo Pigmentado/congênito , Nevo Pigmentado/cirurgia , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/cirurgia , Criança , Feminino , Humanos , MasculinoRESUMO
BackgroundPropranolol is the first-choice treatment for severe infantile hemangioma (IH). However, 10- 30% of lesions relapse after propranolol treatment. The mechanisms underlying IH recurrence after propranolol treatment have not been completely elucidated.MethodsThis study combined an examination of hemodynamic changes with research regarding hemangioma stem cells (hscs) with differentially expressed microRNAs (miRNAs) to identify the factors affecting IH recurrence after propranolol treatment. Hemodynamic changes were monitored in 21 recurrent cases using high-frequency color Doppler ultrasound, and hscs were treated with different concentrations of propranolol. The levels of differentially expressed miRNAs and the activity of related pathways were then compared between 18 recurrent and 20 non-recurrent IH cases.ResultsDuring treatment, lesion depth and vessel density decreased, and the lesion resistance index increased. Obvious lesions and vessel signals were observed in recurrent cases compared with non-recurrent cases. Propranolol effectively inhibited hscs proliferation. Twenty-two differentially expressed miRNAs were found in the recurrent group compared with the non-recurrent group.ConclusionRecurrence may be attributed to a combination of events. Serum biomarkers and drug treatments for IH recurrence must be studied further.
Assuntos
Hemangioma/diagnóstico , Hemangioma/fisiopatologia , Propranolol/uso terapêutico , Recidiva , Biomarcadores/sangue , Feminino , Hemodinâmica , Humanos , Lactente , Recém-Nascido , Masculino , MicroRNAs/metabolismo , Ultrassonografia Doppler , VasoconstriçãoRESUMO
PURPOSE: To identify the factors that may affect outcome in C-ADR and provide the pooled results of postoperative success rate of implanted segment range of motion (ROM), incidence of heterotopic ossification (HO), incidence of radiographic adjacent segment degeneration (r-ASD)/adjacent segment disease (ASD), and surgery rate for ASD. METHODS: We systematically searched in PubMed, Embase, Cochrane library and Web of knowledge from 2001 to May 2015. Two independent reviewers screened the primary records. Eleven questions regarding the effect of patient selection issues and radiographic parameters issues on outcome were posed previously. Studies addressing the framed questions were included for analysis. RESULTS: Twenty-two studies were included for the final analysis. Results showed that number of surgical level (single versus double-level) had no effect on primary clinical outcome and radiographic outcome, surgical level had no effect on clinical and radiographic outcome, and smoking habits had negative effect on clinical outcome. No evidence for the effect of patient's age and pathology category (radiculopathy or myelopathy) on outcome was found. The overall success rate of ROM was 79.4%. ROM of the implanted segment and cervical sagittal alignment had no effects on clinical outcome. The pooled incidences of grade 1-4 HO and grade 3-4 HO were 27.7 and 7.8%, respectively. The pooled incidence of r-ASD and surgery rate for ASD were 42.4 and 3.8%, respectively. CONCLUSIONS: The available evidence showed that most of the pre-selected factors had no effect on outcome after C-ADR, and the ROM success rate, incidence of HO and r-ASD/ASD, and surgery rate for ASD are acceptable. There is a lack of evidence from RCTs for some factors.
Assuntos
Vértebras Cervicais/cirurgia , Degeneração do Disco Intervertebral/cirurgia , Prótese Articular , Radiculopatia/cirurgia , Doenças da Medula Espinal/cirurgia , Substituição Total de Disco/métodos , Fatores Etários , Humanos , Incidência , Degeneração do Disco Intervertebral/complicações , Ossificação Heterotópica/epidemiologia , Medição da Dor , Complicações Pós-Operatórias/epidemiologia , Radiculopatia/etiologia , Amplitude de Movimento Articular , Fatores de Risco , Fumar/epidemiologia , Doenças da Medula Espinal/etiologia , Resultado do TratamentoRESUMO
A series of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives were synthesized in five steps from a common precursor, phthalic anhydride. Most of synthesized phthalazine derivatives showed inhibitory activity against Staphylococcus aureus. One of phthalazine derivatives 5l showed inhibitory activity against all tested bacterial and fungal strains.
Assuntos
Antibacterianos/farmacologia , Ftalazinas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Triazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ftalazinas/síntese química , Ftalazinas/química , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/químicaRESUMO
A series of novel 4-substituted-2-{[(1H-benzo[d]imidazol-2-yl)methyl] thio}-6-methylpyrimidine derivatives were designed, synthesized and evaluated for their cytotoxic activities against four human cancer cell lines and inhibitory activities against five type culture strains in vitro. Some of synthetic pyrimidine-benzimidazol combinations showed good inhibitory activities against Stenotrophomonas maltophilia, especially compounds 7b and 7c. Compounds 7a and 7d exhibited enhanced activities against MGC-803 in vitro, when compared to 5-Fu.
Assuntos
Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Benzimidazóis/química , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Combinatória , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirimidinas/químicaRESUMO
In this study, nano calcium deficient hydroxyapatite (n-DA)/multi-(amino acid) copolymer composite scaffolds were prepared by injection molding foaming method using calcium sulphate dihydrate as a foaming agent. The composite scaffolds showed well interconnected macropores with the pore size of ranging from 100 to 600 µm, porosity of 81 % and compressive strength of 12 MPa, and the compressive strength obviously affected by the porosity. The composite scaffolds could be slowly degraded in phosphate buffered solution (PBS), which lost its initial weight of 61 w % after immersion into PBS for 12 weeks, and the porosity significantly affected the degradability of the scaffolds. Moreover, it was found that the composite scaffolds could promote the MG-63 cells growth and proliferation, and enhance its alkaline phosphatase activity. The implantation of the scaffolds into the femoral bone of rabbits confirmed that the composite scaffolds were biocompatibitive, degradable, and osteoconductive in vivo.
Assuntos
Aminoácidos/química , Durapatita/química , Regeneração Tecidual Guiada/instrumentação , Nanocompostos/química , Osteoblastos/fisiologia , Osteogênese/fisiologia , Alicerces Teciduais , Regeneração Óssea/fisiologia , Substitutos Ósseos/síntese química , Cálcio/química , Linhagem Celular , Força Compressiva , Análise de Falha de Equipamento , Humanos , Teste de Materiais , Nanocompostos/ultraestrutura , Osteoblastos/citologia , Polímeros/síntese química , Porosidade , Desenho de PróteseRESUMO
Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting time = 5.8 ± 0.6 min; compressive strength = 25.6 ± 0.3 MPa) released vancomycin over ~25 days in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8 weeks. Osteomyelitis was cured in 87 % of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71 % for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection.
Assuntos
Cimentos Ósseos/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Portadores de Fármacos/administração & dosagem , Vidro/química , Osteomielite/terapia , Vancomicina/administração & dosagem , Vancomicina/química , Animais , Cimentos Ósseos/química , Boratos/química , Força Compressiva , Portadores de Fármacos/química , Feminino , Injeções Intralesionais , Teste de Materiais , Coelhos , TíbiaRESUMO
This study aims to analyze the whole genome sequencing of E. coli F17 in antagonistic and susceptible Hu sheep lambs. The objective is to investigate the critical mutation loci in sheep and understand the genetic mechanism of sheep resistance to E. coli F17 at the genome level. Antagonist and susceptible venous blood samples were collected from Hu sheep lambs for whole genome sequencing and whole genome association analysis. A total of 466 genes with significant SNPs (p < 1.0 × 10-3) were found. GO and KEGG enrichment analysis and protein interaction network analysis were performed on these genes, and preliminary investigations showed that SNPs on CTNNB1, CDH8, APOD, HCLS1, Tet2, MTSS1 and YAP1 genes may be associated with the antagonism and susceptibility of Hu sheep lambs to E. coli F17. There are still some shortcomings that have not been explored via in vivo and in vitro functional experiments of the candidate genes, which will be our next research work. This study provides genetic loci and candidate genes for resistance of Hu sheep lambs to E. coli F17 infection, and provides a genetic basis for breeding disease-resistant sheep.