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Pityriasis rubra pilaris (PRP) is a rare heterogeneous group of papulosquamous inflammatory disorders with unknown etiology. PRP is often resistant to many conventional therapies which has made more challenging on treatment. More recently, several studies have shown encouraging clinical results of secukinumab in the treatment of PRP in adult, but no studies have explored its effects in children. We herein report a 7-year-old boy with severe type V PRP responded rapidly to secukinumab monotherapy (150 mg once weekly) when conventional therapies have failed. The patient showed rapid and dramatic improvement of erythema, palmoplantar hyperkeratosis, scaling, and itching within only 5 weeks, with no adverse effects. Secukinumab could be considered as a treatment option for refractory PRP in children, as recently reported in adult.
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Ceratose , Pitiríase Rubra Pilar , Adulto , Anticorpos Monoclonais Humanizados , Criança , Humanos , Masculino , Pitiríase Rubra Pilar/diagnóstico , Pitiríase Rubra Pilar/tratamento farmacológico , PruridoRESUMO
The emergence of antibiotic resistant bacteria represents a significant and common clinical problem worldwide as infections are becoming increasingly common. It is urgent to broaden the sources of biomaterials that can prevent both bacterial infection and antibiotic resistance. In this work, oxidized sodium alginate/aminated hyaluronic acid (OSA/AHA) hydrogel with various proportions was developed based on Schiff base reaction. Herein, polydopamine (PDA)-Bmkn2 nanoparticle and sanguinarine were incorporated into hydrogels to enhance antibacterial properties. The prepared PDA-Bmkn2 nanoparticles, with uniform particle size and good dispersion, could serve as a delivery system for Bmkn2. The prepared hydrogels showed appropriate swelling ratio, extremely good mechanical strengths and improved biodegradability. Meanwhile, the Bmkn2 and sanguinarine were released from the hydrogels in a sustainable manner. Furthermore, OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel (less than 10 µg/mL BmKn2 and 0.2 µg/mL sanguinarine) had excellent biocompatibility. Antibacterial experiments confirmed that OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel had effective antimicrobial activity on Escherichia coli and Staphylococcus aureus. Therefore, the prepared injectable hydrogels with good biocompatibility and excellent synergistic antibacterial activity promise great potential for preventing localized bacterial infections.
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OBJECTIVE: To clone, prepare probe for and explore the expression levels of KIAA1173 gene in skin squamous cell carcinoma (SSCC) and investigate its expression, clinical and pathological significance. METHODS: KIAA1173 gene fragment (354 bp) was cloned and its cDNA probe prepared. The expression of KIAA1173 gene in 133 SSCC tissue samples (including 52 specimens of I, 37 specimens of II, 31 specimens of III and 13 specimens of IV) and 47 normal controls were examined by in situ hybridization (ISH). And all specimens were embedded in paraffin. RESULTS: ISH showed brown positive granules in the cytoplasm of parenchymal cells. The positive rate of KIAA1173 mRNA was 38.3% (51/133) in SSCC and 93.6% (44/47) in normal controls. The rate was lower in cancer groups than that in normal tissues (chi(2) = 42.567, P < 0.01). The strongly positive rates were significantly lower in SSCC groups (6.0%, 8/133) than that in normal control (48.9%, 23/47, chi(2) = 44.876, P < 0.01). The negative rates of KIAA1173 mRNA were 53.8% (28/52) in SSCC I, 62.2% (23/37) in SSCC II, 67.7% (21/31) in SSCC III and 76.9% (10/13) in SSCC IV (chi(2) = 4.005, P > 0.05). The negative rates of KIAA1173 mRNA in the dys-good differentiation group (70.5%, 31/44) was higher than that in the good differentiation group (57.3%, 51/89), but there was not significant difference between the two groups (chi(2) = 2.154, P > 0.05). CONCLUSION: KIAA1173 gene is highly expressed in normal skin, but it becomes down-regulated in SSCC. It may play an important role in the development of SSCC.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proteínas de Membrana/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/genéticaRESUMO
We invented a new method to make microarrays using nuclei extracted from paraffin-embedded tissues or cultured cells. A blank recipient paraffin block with 10 x 10 cores was constructed and sectioned to make the mold for the cell arrays. The sections of paraffin were mounted on poly-L-lysine-coated slides. Prepared nuclei or cells were injected into the cores of the paraffin mold. The slides were dried and dewaxed and nuclei or cell arrays were made. Using this method, we successfully made microarrays of nuclei extracted from diffuse large B-cell lymphoma paraffin-embedded tissues, nasopharyngeal cancer and lymphoma cell lines. This technique resulted in a paraffin-embedded cell preparation that yielded a cell density of approximately 500 to 1000 or 800 cells on average per 0.6-mm-diameter core. The microarrays were successfully used in fluorescence in situ hybridization, mRNA in situ hybridization, and cytohistochemical staining.
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Linfoma de Células B/genética , Linfoma Difuso de Grandes Células B/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Linhagem Celular Tumoral , Núcleo Celular/genética , Genes de Imunoglobulinas , Genes bcl-2 , Humanos , Imuno-Histoquímica , Hibridização In Situ , Hibridização in Situ Fluorescente , Linfoma de Células B/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas de Membrana/genética , NF-kappa B/metabolismo , Inclusão em Parafina , RNA Mensageiro/genética , RNA Neoplásico/genéticaRESUMO
BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a group of genetically heterogeneous diseases. Mutations in transglutaminase (TGase) 1 gene (TGM1, OMIM 190195) have been implicated in ARCI. However, little is known about TGM1 mutations in the Chinese population, and no functional studies have investigated the biological effect of mutant TGM1 on human epidermal keratinocytes (HaCaT) cells. OBJECTIVES: To identify the pathogenic mutations of TGM1 gene in two Chinese siblings with ARCI and gain insight into functional consequences of these mutations. METHODS: Fifteen exons and flanking splice sites of TGM1 gene were amplified by polymerase chain reaction and then underwent bidirectional Sanger sequencing. The HaCaT cells were transfected with lentiviral vectors, which overexpressed either wild-type or mutant TGM1 cDNAs with deleted homeodomain. Cell proliferation and cell cycle progression were detected. The expression of cyclin D1, cyclin B1, CDK4, TGM1, K10, involucrin, and filaggrin proteins were investigated by Western blot analysis. RESULTS: We found two compound heterozygous missense mutations (c.515C>T, R143C in exon 3 and c.759C>T, S212F in exon 4) in both siblings. HaCaT cells transfected with mutant TGM1 cDNAs displayed a lower growth rate and delayed S phase while overexpression of wild-type TGM1 cDNAs led to accelerated growth. HaCaT cells transfected with mutant TGM1 cDNAs displayed lower expression of differentiation markers such as involucrin and filaggrin. Our findings suggest that the compound heterozygous missense (c.515C>T, R143C) mutations in exon 3 and missense (c.759C>T, S212F) mutations in exon 4 result in the phenotype of ARCI. TGM1 mutations can suppress keratinocyte growth and cornified cell envelope formation.
Assuntos
Eritrodermia Ictiosiforme Congênita/genética , Transglutaminases/genética , Povo Asiático/genética , Linhagem Celular , Proliferação de Células/genética , Criança , China , Éxons/genética , Feminino , Proteínas Filagrinas , Genes Recessivos , Heterozigoto , Humanos , Eritrodermia Ictiosiforme Congênita/patologia , Proteínas de Filamentos Intermediários/metabolismo , Queratinócitos/fisiologia , Masculino , Mutação de Sentido Incorreto , Linhagem , Precursores de Proteínas/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/genética , TransfecçãoRESUMO
OBJECTIVE: To establish a 6-10B cell line with stable expression of KIAA1173 gene and study the biological behaviors of the cells. METHODS: The total RNA was extracted from normal skeletal muscular tissues for cloning of KIAA1173 gene by means of RT-PCR which was subsequently introduced into pcDNA3.1 (+) vector. The recombinant eukaryotic expression vector pcDNA 3.1(+)-KIAA1173 was constructed and identified by endonuclease digestion and sequencing before transfection into 6-10B cells via lipofectamine with the empty vector as the control. The positive cell clones were obtained by G418 selection. Stable expression of KIAA1173 gene in the transfected 6-10B cells was determined by RT-PCR, in situ hybridization and immunocytochemistry, and the biological behaviors of the transfected cells were observed by MTT assay, cell invasion assay and tumorigenesis assay in nude mice. RESULTS: High expression of KIAA1173 at both mRNA and protein levels was observed in the transfected 6-10B cells. The capability of proliferation, invasion and tumorgenicity of the KIAA1173-transfected cells in nude mice was lowered in comparison with those of the cells transfected with pcDNA3.1 (+) vector (P<0.05). CONCLUSIONS: KIAA1173 genes may function as a potential tumor suppressor of nasopharyngeal carcinoma both in vitro and in vivo. The 6-10B cell line expressing KIAA1173 has been obtained, which can be helpful for further study of KIAA1173 gene.
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Proteínas de Membrana/genética , Neoplasias Nasofaríngeas/genética , Transfecção , Animais , Linhagem Celular Tumoral , Clonagem Molecular , Células Eucarióticas/metabolismo , Genes Supressores de Tumor , Vetores Genéticos , Humanos , Proteínas de Membrana/biossíntese , Camundongos , Camundongos Nus , Neoplasias Nasofaríngeas/patologia , Transplante de Neoplasias , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genéticaRESUMO
OBJECTIVE: To observe the drug release of podophyllotoxin liposome and the drug retention in the skin. METHODS: Two liposome suspensions containing respectively podophyllotoxin dipalmitoylphosphatidylcholine (DPPC) and soya bean lecithin were prepared ultrasonically. Podophyllotoxin anhydride and the liposome suspensions were applied onto the skin of young pigs to observe the drug retention in the skin at different time points in the following 2 days, with exclusive liposome or anhydride serving as control. RESULTS: One hour after application of podophyllotoxin anhydride, a peak of the drug concentration in the skin occurred followed by immediate declination, a process not observed after the application of bean lecithin liposome due to gradual drug release that produced drug concentration constantly much higher than that of podophyllotoxin anhydride. A peak concentration was also observed 4 h after application of podophyllotoxin DPPC liposome, which then declined slowly to and stabilized at a higher level than that of bean lecithin liposome of anhydride within 48 h. CONCLUSION: DPPC liposome-embedded podophyllotoxin better targets the drug to the skin after application, and is a suitable preparation for topical skin application.
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1,2-Dipalmitoilfosfatidilcolina , Antineoplásicos Fitogênicos/farmacologia , Podofilotoxina/farmacologia , Pele/efeitos dos fármacos , Administração Tópica , Animais , Fluorescência , Lipossomos , Pele/patologia , SuínosRESUMO
OBJECTIVE: To investigate the changes of serum concentration of podophyllotoxin after topical application of liposome podophyllotoxin suspension on rat skin. METHODS: SD rats were used in this study, which were divided into test group (n=48) to receive application of liposome podophyllotoxin (0.5 % ) suspension and control group (n=48) treated with 0.5 % podophyllotoxin alcohol solution. Blood samples were obtained from the heart at 1, 2, 4, 6, 8, 10, 12 and 24 h respectively after drug application, and the serum concentration of podophyllotoxin was determined by spectrofluorometry. RESULTS: The area under the curve of plasma drug concentration of the control group was 2.3-fold greater than that of the test group. Eight hours after drug application, the serum concentration of podophyllotoxin reached the peak in the test group, while in the control group, only two hours was needed to reach the peak. The peak serum level of podophyllotoxin in the test group were significantly lower than that of the control group (166.395 +/- 14.634 ng/ml vs 378.603 +/- 26.105 ng/ml, P<0.001). CONCLUSION: The systemic absorption of podophyllotoxin in rats after its topical application in liposome suspension is significantly lower than that after application of 0.5 % podophyllotoxin alcohol solution, therefore the systemic toxicity may be reduced.
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Podofilotoxina/sangue , Podofilotoxina/farmacocinética , Pele/metabolismo , Administração Cutânea , Algoritmos , Animais , Área Sob a Curva , Feminino , Lipossomos , Masculino , Podofilotoxina/administração & dosagem , Podofilotoxina/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Absorção Cutânea , Espectrometria de FluorescênciaRESUMO
OBJECTIVE: To prepare podophyllotoxin-dipalmitoylphosphatidylcholine (PPT-DPPC) proliposomes (PPT-DPPC-PL) for improvement of the stability of PPT-DPPC liposome. METHODS: Freeze-drying method was used to prepare PPT-DPPC-PL, and the particle morphology, size range, encapsulation efficiency and stability of PPT-DPPC liposome were investigated. RESULTS: After hydration of PPT-DPPC-PL, PPT-DPPC liposome appeared multivesicular under electron microscope and the particles were distributed homogeneously with an average particle size of 1.45+/-0.38 microm. The encapsulation efficiency of PPT was 72.3%, and after storage at 4 to 40 degrees Celsius; for 1 to 6 months, the proliposome remained stable. CONCLUSION: The prepared PPT-DPPC-PL particles by freeze-drying method are evenly distributed. The preparation method is relatively simple with higher embedding ratio and better stability.
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1,2-Dipalmitoilfosfatidilcolina/administração & dosagem , Podofilotoxina/administração & dosagem , Estabilidade de Medicamentos , Liofilização , Lipossomos , Tamanho da Partícula , TemperaturaRESUMO
Proteus syndrome (PS) is a rare and sporadic disorder characterized by overgrowth of multiple tissues and a propensity to develop particular neoplasms. The clinical manifestations of PS include macrodactyly, vertebral abnormalities, asymmetric limb overgrowth and length discrepancy, hyperostosis, abnormal and asymmetric fat distribution, asymmetric muscle development, connective tissue nevi, and vascular malformations. We report a 16-year old female patient who manifested a number of these complications and review the Chinese literature about the diagnosis, natural history, and management of PS.
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Retinoids have been used for years as monotherapy and/or in combination for treatment and suppression of cutaneous malignancies in patients with basal cell nevus syndrome, xeroderma pigmentosum, or cutaneous T-cell lymphoma (CTCL) basal cell carcinoma (BCC). We report 4 cases with BCC confirmed by histopathology who were treated by short-term systemic acitretin combined with retinoic acid 0.1% cream. The 4 cases with BCC showed good response to the treatment without severe adverse effects during treatment and follow-up. The finding suggests that acitretin may be an appropriate treatment option for elderly patients who require less invasive treatment for BCC.
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BACKGROUND & OBJECTIVE: Although the molecular etiology of nasopharyngeal carcinoma (NPC) is still unknown, studies showed that there are NPC-associated tumor suppressor genes residing in chromosome 3p21-22. KIAA1173 gene, locates at 3p22.1, was characterized as a new carcinoma-related gene, while its correlation to tumorigenesis of NPC hasn't been reported yet. This study was to detect the expression of KIAA1173 gene in NPC tissues and cell lines, and investigate its involvement in NPC. METHODS: KIAA1173 gene fragment (354 bp) was cloned, and the cDNA probe was prepared. The expression of KIAA1173 gene in 73 nasopharyngeal tissue samples (including 41 specimens of NPC, 18 atypical hyperplasia epithelia, and 14 normal nasopharyngeal mucosa epithelia) and 6 NPC cell lines (including CNE1, CNE2, HNE1, HNE2, 6-10B, and 5-8F) were examined using tissue microarray technique by in situ hybridization (ISH). RESULTS: The positive rates of KIAA1173 mRNA were 21.9% (9/41) in NPC, 83.3% (15/18) in atypical hyperplasia epithelia, 92.8% (13/14) in normal nasopharyngeal mucosa epithelia, and 0 in all NPC cell lines. Its strongly positive rate was significantly lower in NPC than in atypical hyperplasia epithelia and normal mucosa epithelia (0 vs. 38.9% and 64.3%, P < 0.001). In 38 specimens of NPC with infiltrated lymphocytes, the positive rate of KIAA1173 mRNA was significantly lower in cancer cells than in tumor infiltrating lymphocytes (23.7% vs. 44.7%, P < 0.05); the expression of KIAA1173 in cancer cells was negatively related to that in tumor infiltrating lymphocytes (kappa = -0.337, P < 0.05). CONCLUSIONS: KIAA1173 gene is strongly expressed in normal nasopharyngeal mucosa epithelia, but down-regulated in NPC. It may be associated with the tumorigenesis of NPC. Tissue microarray;
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Células Epiteliais/metabolismo , Proteínas de Membrana/biossíntese , Neoplasias Nasofaríngeas/metabolismo , Nasofaringe/citologia , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização In Situ , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mucosa Nasal/citologia , Neoplasias Nasofaríngeas/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Análise Serial de TecidosRESUMO
OBJECTIVES: To explore a sensitive and specific method for detection of bcl-2/IgH gene rearrangement in diffuse large B cell lymphoma (DLBCL), and verify the credibility of the established method. METHODS: bcl-2/IgH hemi-nested PCR primers were designed using the professional primer design software. Fifty-two samples of pathologically diagnosed DLBCL and 10 fresh tonsil tissues were amplified using hemi-nested touch down-PCR to detect bcl-2/IgH gene rearrangement. The PCR products were cloned and sequenced. RESULTS: bcl-2/IgH gene rearrangement was detected in 6 of 52 DLBCL samples and 2 of 10 fresh tonsil tissues using one-way method. By using the hemi-nested PCR for the second round amplification, 5 of DLBCL were positive, but all of the fresh tonsil tissues were negative. The positive PCR products were sequenced and analyzed on the Internet, 3 of 8 cases obtained by one-way method were false positive, 5 positive cases amplified using hemi-nested PCR were all bcl-2/IgH gene rearrangement. PCR products of 3 false positive cases were homologous to BAC331191 and LLNLR-245D11 in human chromosome 19 and RP11-498P10 in chromosome 1. CONCLUSION: There are false positive results using common primers for detecting bcl-2/IgH gene rearrangement. The mechanism may be that highly homologous sequences to human genome exist in commonly used primers. The specificity of the diagnosis could be improved by hemi-nested PCR using the combination of primers we designed and the traditional ones.