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To investigate the diagnostic value of dermoscopy in defining the tumor margin of basal cell carcinoma (BCC) for the appropriate surgical margin. A total of 107 BCC patients were enrolled for this study. The tumor boundaries were observed by naked eye and dermoscope respectively, and 5 mm outward was used as surgical margin according to the dermoscopy-defined margin. Pathological examinations were performed at 2 mm intervals in the direction previously marked and the effect was assessed accordingly. There were still 16.8% of patients whose visual margin was insufficient to the dermoscopy-detected margin. With 2 mm excision margin from the dermoscopy-guided tumor margin, excision range in 12 patients (11.2%) proved to be inadequate, but only 18 surgical margins (4.2%) in the whole 428 excision margin specimens proved to be tumor-positive. While with 4 mm margin, residual lesion was observed in 2 (0.5%) of 107 BCC patients, and positive margin was found in 2 (0.3%) of 428 margin specimen. There has been no recurrence in our study so far. Dermoscopy is superior to visual inspection for defining BCC tumor margin. Under preoperative dermoscopy detection, a 4 mm excision margin of BCC can achieve a radical resection rate of 98.1%, and 92.3% for a 2 mm excision margin of pigmented BCC.
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Carcinoma Basocelular , Neoplasias Cutâneas , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/cirurgia , Dermoscopia , Humanos , Margens de Excisão , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgiaRESUMO
A series of novel biphenyl-furocoumarin derivatives were synthesized based on the nuclear structure of imperatorin and identified by IR, 1H NMR, 13C NMR and MS, and evaluated for their ability to relax vessel on isolated rat mesenteric artery, basilar artery and renal artery, respectively. The majority of compounds demonstrated potent vasodilatation, and compound 8e expressed the highest activity (EC50 = 0.56 µM) in MA. Compounds with fluorine at 2-position of 5-phenyl get better activity than others with chlorine or bromine, and the compounds containing a bulky structure had relatively low activity, such as 8c (EC50 = 22.39 µM) in MA. As a follow-up, 8e, 10e, and 8c were docked into L-calcium channel (PDB code: 3G43) to explain the difference in the activity of the compounds.
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Furocumarinas , Vasodilatadores , Animais , Compostos de Bifenilo , Estrutura Molecular , Ratos , Relação Estrutura-AtividadeRESUMO
Hippocampal SIRT1 dysfunction and gene variation have previously been found potentially involved in depressive and anxiety disorders. However, the exact role of SIRT1 in post-traumatic stress disorder (PTSD) is not well understood. Here, we employed multiple genetic and pharmacological approaches targeting SIRT1 to verify the effects of SIRT1 on SPS-induced PTSD-like behaviors and its potential cellular and molecular mechanisms. We first demonstrated that Sirt1 knockout mice showed milder PTSD-like behavior after single prolonged stress (SPS) induction than wild type mice. Moreover, the expression of SIRT1 in the ventral CA1 (vCA1) region of hippocampus showed no significant changes following SPS induction, but the activity of SIRT1 enzyme was significantly increased post-SPS. Osmotic administration of EX527 in vCA1, a SIRT1 inhibitor, was shown to normalize the SIRT1 activity in SPS mice. Mechanically, EX527 rescued the acetylation of helix-loop-helix transcription factor 2 (NHLH2) and transcriptionally inhibited the increase of MAO-A expression in the vCA1, which thus suppressed the decomposition of the neurotransmitter serotonin into 5-hydroxydoleacetic acid (5-HIAA). Morphologically, Golgi staining showed that EX527 treatment improved the abnormal neuronal structure plasticity in the vCA1 region after SPS, including reversing the atrophic dendrites and the decreased dendritic spines. Finally, SIRT1 inhibitor effectively alleviated fear conditioning responses and anxiety-like behaviors. Our study first demonstrated that the development of PTSD-like behaviors was causatively related to the abnormal increase of SIRT1 activity in the ventral hippocampal CA1 region. And we also provided evidence that SIRT1 inhibition might exert therapeutic effects on PTSD by maintaining serotonin homeostasis through transcriptional inhibition of MAO-A, and thereby remodeled synaptic plasticity in the vCA1 region.
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Carbazóis/uso terapêutico , Plasticidade Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Sirtuína 1/genética , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Região CA1 Hipocampal/efeitos dos fármacos , Deleção de Genes , Homeostase/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monoaminoxidase/metabolismo , Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismoRESUMO
BACKGROUND: Nail matrix histopathologic examination is still the criterion standard to diagnose longitudinal melanonychia (LM). OBJECTIVE: To introduce modified shave surgery combined with the nail window technique for managing LM and evaluate the postoperative outcome of the procedure. METHODS: We retrospectively reviewed the medical records of 67 patients with LM who underwent shave surgery combined with the longitudinal-strip nail window technique at our institution from March 2015 to June 2018. RESULTS: Pathologic diagnosis was accessible in all cases, and 60 cases were assessable for the postoperative outcomes. A total of 45 cases (75.0%) had no postoperative nail dystrophy, and recurrence of nail pigmentation was found in only 8 cases (13.3%). LIMITATIONS: This was a retrospective study. CONCLUSION: Modified shave surgery combined with the nail window technique is the preferable management for LM cases, with limited postoperative nail dystrophy and recurrence of pigmentation.
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Procedimentos Cirúrgicos Dermatológicos/métodos , Doenças da Unha/cirurgia , Unhas/patologia , Transtornos da Pigmentação/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Biópsia , Criança , Pré-Escolar , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Procedimentos Cirúrgicos Dermatológicos/instrumentação , Diagnóstico Diferencial , Feminino , Humanos , Lasers de Gás/uso terapêutico , Masculino , Melanoma/diagnóstico , Melanoma/patologia , Pessoa de Meia-Idade , Doenças da Unha/diagnóstico , Doenças da Unha/patologia , Unhas/cirurgia , Transtornos da Pigmentação/diagnóstico , Transtornos da Pigmentação/patologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Recidiva , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
RACK1 is a crucial scaffold and anchoring protein, which plays a vital role in multiple signaling pathways of tumorigenesis. The aim of the present study was to identify the correlation between expressions of RACK1 and malignant degrees in colorectal carcinoma (CRC) patients. All together 157 CRC patients were enrolled, and their clinical data were analyzed. Expressions of RACK1 in CRC and pericarcinous tissues in these patients were determined by RT-PCR, Western-blot, and immunohistochemistry, respectively. The correlation between RACK1 expressions and histological grades, as well as lymph node metastasis was evaluated. Results showed that the expressions of RACK1 were positively correlated with differentiation level and lymph node metastasis in CRC patients.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas de Ligação ao GTP/genética , Expressão Gênica , Proteínas de Neoplasias/genética , Receptores de Superfície Celular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/metabolismo , Feminino , Proteínas de Ligação ao GTP/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Quinase C Ativada , Receptores de Superfície Celular/metabolismoRESUMO
BACKGROUND: Onychocryptosis is a common pathological condition requiring clinical intervention. Selecting an appropriate and effective treatment based on individual patient circumstances is crucial. METHODS: We compared the efficacy and safety of the modified Noel's technique and matrix phenolization in 107 participants with onychocryptosis. Participants were divided into two groups: 75 nails (73 patients) were treated with the modified Noel's technique (modified Noel's group), while 42 nails (34 patients) were treated with matrix phenolization (Phenol group). Outcomes on clinical cure rates and postoperative complications from both groups were collected. Additionally, the efficacy of the modified Noel's technique was assessed in 31 nails with stage IV onychocryptosis. RESULTS: After 18 months, among the remaining 102 patients (110 nails), the modified Noel's group exhibited fewer complications (5.88% vs. 45.2%, P < 0.001) with similar cure rates (P = 0.62). Furthermore, there was a shorter healing time in the modified Noel's group (13.5 ± 1.4 vs. 27.6 ± 2.3 days, P < 0.001). Postoperative pain was notable in the modified Noel's group on the first postoperative day (P < 0.001), with a significant decrease in the pain score 2 weeks after surgery (P = 0.407). Postoperative nail plate narrowing was observed in the Phenol group (33%). Moreover, the modified Noel's technique achieved a 100% cure rate in stage IV patients. CONCLUSIONS: The modified Noel's technique, offering precise excision of the proliferative nail fold and strategic suturing, is suitable for stage IV patients and for those who find significant aesthetic impact unacceptable following narrowed plate postmatrix phenolization.
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Objective: To explore the pattern of empathy characteristics in male patients with schizophrenia (SCH) and to examine whether empathy deficit is associated with impulsivity and premeditated violence. Methods: One hundred and fourteen male SCH patients were enrolled in this study. The demographic data of all patients were collected and the subjects were divided into two groups, namely, the violent group, including 60 cases, and the non-violent group, comprising 54 cases, according to the Modified Overt Aggression Scale (MOAS). The Chinese version of the Interpersonal Reactivity Index-C (IRI-C) was used to evaluate empathy and the Impulsive/Predicted Aggression Scales (IPAS) was employed to assess the characteristics of aggression. Results: Among the 60 patients in the violent group, 44 patients had impulsive aggression (IA) and 16 patients had premeditated aggression (PM) according to the IPAS scale. In the violent group, the scores of the four subfactors of the IRI-C, i.e., perspective taking (PT), fantasy (FS), personal distress (PD), and empathy concern (EC), were significantly lower than in the non-violent group. Stepwise logistic regression showed that PM was independent influencing factor for violent behaviors in SCH patients. Correlation analysis revealed that EC of affective empathy was positively correlated with PM but not with IA. Conclusion: SCH patients with violent behavior had more extensive empathy deficits compared with non-violent SCH patients. EC, IA and PM are independent risk factors of violence in SCH patients. Empathy concern is an important index to predict PM in male patients with SCH.
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Objective: To investigate the diagnostic value of dermoscopy in defining the tumor margin of cutaneous squamous cell carcinoma (cSCC) for the appropriate surgical margin. Methods: A total of 90 cSCC patients were enrolled in the study. All patients were recruited into two groups: those who preserved intact macroscopic features of neoplasms without or after incisional biopsy and those with uncertain residual tumors after excisional biopsy. A dermoscopy-defined surgical margin of 8mm outward was used according to the tumor boundaries observed with the naked eye and dermoscopy. All excised tumor specimens were divided into serial sections according to the four "3, 6, 9, 12" directions at every 4-mm interval from the dermoscopy-detected tumor margin. Pathological examination was performed at 0 mm, 4 mm, and 8 mm margins to confirm tumor remnants. Results: Retrospective analysis of dermatoscopic results showed inconsistent clinical and dermatoscopic borders in 43 of 90 cases (47.8%). The ability of dermoscopy to detect tumor borders showed no statistical difference between the two groups (p > 0.05). In the unbiopsy or incisional biopsy group, 66.6% of the tumors were resected with a 4-mm margin and 98.3% with an 8-mm margin, with significant differences (p = 0.047). For patients with inconspicuous clinical evidence of residual tumor after excisional biopsy, the tumor clearance rate was 53.3% at 0 mm, 93.3% at 4 mm, and 100.0% at 8 mm. Statistically significant differences were noted between 0 mm and 4 mm (p = 0.017), as well as between 0 mm and 8 mm (p = 0.043) but did not differ between 4 mm and 8 mm (p > 0.05). Conclusions: Dermoscopy defined the tumor margin of cSCC better than visual inspection alone. Direct dermoscopic-guided surgery with at least 8-mm expansion was recommended for high-risk cSCC. Dermoscopy also assisted in identifying surgical margins at the healing biopsy site, making 8 mm still the recommended expansion range.
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Background: Onychopapilloma is generally recognized as a benign tumor of the nail bed and distal matrix. However, the origin of onychopapilloma has not been explained yet. Objective: To clarify the origin of onychopapilloma, we detected the expression patterns of hair-related keratins and epithelial keratins, which are expressed specifically in the nail unit. Materials and methods: The clinical and histopathologic features of 11 patients with onychopapilloma were analyzed, and the expression patterns of hair-related and epithelial keratins were detected. Results: Histologically, all subjects showed acanthosis, papillomatosis and matrix metaplasia within the nail bed. Immunohistochemically, the expression pattern of keratins in our standard nail unit was consistent with previous reports. "Nail matrix-related keratins" HK31, HK34, HK85, and HK86 were only expressed in the nail matrix, and "Nail bed-related keratins" HK75 and K6/K16 were only expressed in the nail bed. However, in onychopapilloma, whether adjacent to the matrix or in the distal nail bed, all cases were positive for nail bed-related keratins and HK31 but negative for other nail matrix-related keratins. Conclusion: Our study suggests that onychopapilloma may originate from the nail bed rather than the nail matrix. Furthermore, the expression of nail bed-related keratins and HK31 could be used as diagnostic markers of onychopapilloma.
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The nail apparatus is the largest and most complex skin appendage. Defects in this unit can result in significant functional insufficiency and cosmetic disfigurement. Common nail deformities include split nail, short nail, onycholysis, nail malalignment, hooked nail, and absent nail. Currently, surgical repair is the primary treatment for such deformities. Based on the etiological and anatomical classifications, one or more appropriate operations can be selected to repair nail unit deformities. These include autologous fat grafting, longitudinal cicatrectomy, Z-plasties, nail bed elongation, split-thickness sterile matrix grafting, volar V-Y advanced flap reconstruction, sterile matrix particle grafting, germinal matrix flaps, and germinal matrix grafting. This review discusses the fundamental classification of nail unit deformities, common reconstructive surgical techniques, and their features.
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Doenças da Unha , Procedimentos de Cirurgia Plástica , Humanos , Retalhos Cirúrgicos , Unhas/cirurgia , Doenças da Unha/cirurgia , Transplante de Pele/métodosRESUMO
ABSTRACT: Recently, the coronavirus disease 2019 (COVID-19) epidemic has greatly threatened global public health. The responsibility of healthcare-associated infection control professionals (ICPs) is to prevent and control the nosocomial infections. The mental health status of ICPs deserves more attention, however, the correlational research is still lacking. This study aims to investigate the incidence and risk factors of mental health status among ICPs in China during the outbreak of COVID-19.A national cross-sectional survey was performed. The online questionnaire was completed by 9228 ICPs from 3776 hospitals throughout China. Data collection tools were used, including demographics data questionnaire, the Chinese version of the 12-item general health questionnaire (GHQ-12) and the Chinese version of the psychological capital questionnaire (PCQ) for medical staff. Univariate and multivariable analyses were conducted.The total score of mental health of Chinese ICPs was 3.45â±â2.57. 5608 (60.77%) ICPs might have mental health problems. The psychological capital was in the upper-middle level with an average score of 3.72â±â0.38. An increased mental health problem risk was associated with the greater self-efficacy and working in the public hospital; a significantly lower risk was obtained by working in the second-class hospital rather than in the third-class hospitals. Besides, mental health problem risk of ICPs working in hospitals of the western economic region or northeast economic region was more significant than that in hospitals of the central economic region. However, a lower risk was caused by the unmarried than married, and working years in department ≤1âyear contributed to the lower risk than that >20âyears. Moreover, fewer working hours per week, higher values of hope, and optimism each were contributed to a lower risk.Chinese healthcare-associated ICPs were under different levels of mental health problems in fighting against COVID-19. More importantly, we should actively deal with the mental health problem of ICPs and help them get rid of psychological disorders.
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COVID-19 , Infecção Hospitalar , Profissionais Controladores de Infecções , Controle de Infecções , Exposição Ocupacional , Estresse Ocupacional , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/psicologia , China/epidemiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Estudos Transversais , Feminino , Humanos , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Profissionais Controladores de Infecções/psicologia , Profissionais Controladores de Infecções/estatística & dados numéricos , Masculino , Saúde Mental/estatística & dados numéricos , Exposição Ocupacional/prevenção & controle , Exposição Ocupacional/estatística & dados numéricos , Estresse Ocupacional/epidemiologia , Estresse Ocupacional/etiologia , Estresse Ocupacional/prevenção & controle , Medição de Risco , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
5-Hydroxymethylfurfural (5-HMF) is present in numerous carbohydrate-containing consumer products and is readily converted into two oligomers (II and III) by acid-catalyzed transformations. Previous studies have demonstrated various undesirable effects of 5-HMF at relatively high concentrations. In this study, we demonstrate that 5-HMF and its two oligomers exert neurotoxic effects in vivo and in vitro. All three substances blocked the proliferation of PC12 and HT22 cells at the S or G2-M phase in dose- and time-dependent manners. In addition, [Ca2+]i and reactive oxygen species levels were both significantly increased by treatment with these substances at 100 µM, individually, compared with the control group. Although no motor and cognitive deficits are observed, 5-HMF and III can induce anxiety- and depression-like behavior in adolescent mice at administered doses of 0.15 mg kg-1 and 1.5 mg kg-1in vivo, which are close to or less than the reported 24 h dietary intake of 5-HMF in humans. Together, our findings suggest the need for close monitoring of the content of these substances in food, as well as the need for studies on the effects of long-term exposure to them.
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Carboidratos/química , Furaldeído/análogos & derivados , Sistema Nervoso/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Animais , Comportamento Animal/efeitos dos fármacos , Cálcio/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Análise de Alimentos , Furaldeído/química , Furaldeído/toxicidade , Camundongos , Atividade Motora , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Delayed cognitive impairment (DCI) after subarachnoid hemorrhage (SAH) is one of the most common sequelae in patients. This study aimed to investigate the characteristics of the course and glutamatergic pathogenesis of DCI after SAH in mice. METHODS: A SAH mouse model of internal carotid puncture was used. Depressive and cognitive behaviors were detected by forced swimming and sucrose preference tests and Morris water maze test, respectively. Microdialysis and high-performance liquid chromatography (HPLC) were used to detect the interstitial glutamate. The expressions of histone deacetylases (HDACs), glutamate transporters, and glutamate receptors were examined. Primary astrocytes magnetically sorted from adult mice were cultured for glutamate uptake assay and protein and mRNA detection. Selective HDAC2 inhibitor and glutamate transporter-1 (GLT-1) inhibitor administered via were intraperitoneal injection to evaluate their effects on DCI in SAH mice. RESULTS: Depression and memory impairment lasted for more than 12 weeks and peaked at 8 weeks after SAH. Interstitial glutamate accumulation in the hippocampus and impaired glutamate uptake in astrocytes of the SAH mice were found during DCI, which could be explained by there being a significant decrease in GLT-1 expression but not in glutamate and aspartate transporter (GLAST) in hippocampal astrocytes. Meanwhile, the phosphorylation level of excitatory glutamate receptors (GluN2B and GluA1) in the hippocampus was significantly reduced, although there was no significant change in the expression of the receptors. Importantly, the expression of HDAC2 increased most significantly in astrocytes after SAH compared with that of other subtypes of HDACs. Inhibition of HDAC2 markedly rescued the decrease in GLT-1 expression after SAH through transcriptional regulation. Behavioral results showed that a selective HDAC2 inhibitor effectively improved DCI in SAH mice, but this effect could be weakened by GLT-1 inhibition. CONCLUSIONS: In summary, our study suggests that the dysfunction of GLT-1-mediated glutamate uptake in astrocytes may be a key pathological mechanism of DCI after SAH, and that a specific inhibitor of HDAC2 may exert a potential therapy.
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A fluorescent probe (Fluo-HMF) was developed via introduction of a furfural moiety into the fluorescein molecular skeleton, aiming at specially labeling cell membrane of mast cells. To illustrate its specificity, we designed and synthesized a series of fluorescent compounds based on fluorescein molecular skeleton. The fluorescent properties of Fluo-HMF were investigated, which were in accordance with theoretical calculations. Compared with other fluorescein derivatives, Fluo-HMF could specially label RBL-2H3 cells. The results suggested that Fluo-HMF could be used as a fluorescent probe for bioimaging on some related research of allergic mechanism.
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Fluoresceína/química , Corantes Fluorescentes/síntese química , Furaldeído/análogos & derivados , Microscopia de Fluorescência , Animais , Linhagem Celular , Corantes Fluorescentes/química , Furaldeído/química , Mastócitos/citologia , Mastócitos/patologia , Teoria Quântica , Ratos , Espectrometria de FluorescênciaRESUMO
AIM: To investigate the effects and mechanisms of miR-451a in the tamoxifen (TAM) resistance of breast cancer cells. MATERIALS AND METHODS: TAM sensitive cells (MCF-7) and resistant cells (LCC2) were employed in the study. The lentivirus vectors of Lv-miR-451a, Lv-miR-451a sponge, and Lv-miR-451a NC were employed to increase or decrease the expression of miR-451a, respectively. SiRNA to 14-3-3ζ was used to inhibit expression of 14-3-3ζ. MTT assay was utilized to detect breast cancer cell proliferation. AnnexinV-FITC binding assay was used to detect apoptosis. Expression of ERα, 14-3-3ζ and miR-451a were measured by qRT-PCR and Western blot analysis. Interactions between 14-3-3ζ and ERα were investigated by co-immunoprecipitation. LC3-II surface expression and intracellular autophagosomes were observed by Western blot and electron microscopy. KEY FINDINGS: Over-expression of miR-451a can enhance MCF-7 and LCC2 cell sensitivity to TAM. Opposite effects were elicited by knocking down miR-451a. TAM treatment can up-regulate 14-3-3ζ expression, and down-regulate ERα expression. 14-3-3ζ and ERα were shown to interact. Over-expression of miR-451a decreased 14-3-3ζ expression and increased ERα expression, suppressing cell proliferation, increasing apoptosis, and reducing activation of p-AKT and p-mTOR. R18 can significantly decrease cell proliferation and increase apoptosis. R18 and 14-3-3ζ siRNA can rescue the effects of down-regulation of ERα by knocking down miR-451a. Over-expression of miR-451a inhibits autophagy, knocking-down miR-451a stimulates autophagy. SIGNIFICANCE: MiR-451a functions as a suppressor of resistance to TAM through regulating autophagy, the expression of 14-3-3ζ and ERα. This suggests miR-451a to be a potential target for reversing resistance to TAM.
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Proteínas 14-3-3/biossíntese , Autofagia/fisiologia , Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/biossíntese , MicroRNAs/biossíntese , Tamoxifeno/uso terapêutico , Proteínas 14-3-3/antagonistas & inibidores , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Autofagia/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Relação Dose-Resposta a Droga , Receptor alfa de Estrogênio/antagonistas & inibidores , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Tamoxifeno/farmacologiaRESUMO
Multidrug-resistant Acinetobacter baumannii has become a worldwide problem, and methylation of 16S rRNA has recently emerged as a new mechanism of resistance to aminoglycosides, which is mediated by a newly recognized group of 16S rRNA methylases. 16S rRNA methylase confers a high-level resistance to all 4,6-substituted deoxystreptamine aminoglycosides that are currently used in clinical practice. Some of the A. baumannii isolates have been found to coproduce extended-spectrum beta-lactamases (ESBLs), contributing to their multidrug resistance. The aim of this study was to detect the determinants of the 16S rRNA methylase genes armA, rmtA, rmtB, rmtC, rmtD, rmtE, and npmA, the modifying enzyme genes aac(6')-Ib, ant(3â³)-Ia, aph(3')-I, and the extended-spectrum beta-lactamase genes bla(TEM), bla(SHV), and bla(CTX-M-3) among A. baumannii isolates in northeastern Sichuan, China. Minimum inhibitory concentrations (MICs) of 21 different antimicrobial agents against the A. baumannii isolates were determined. The clinical isolates showed a high level of resistance (MICâ§256 µg/ml) to aminoglycosides, which ranged from 50·1 to 83·8%. The resistances to meropenem and imipenem, two of the beta-lactam antibiotics and the most active antibiotics against A. baumannii, were 9·1 and 8·2%, respectively. Among 60 amikacin-resistant isolates, only the 16S rRNA methylase gene armA was found to be prevalent (66·7%), but the other 16S rRNA methylase genes rmtA, rmtB, rmtC, rmtD, rmtE, and npmA were not detected. The prevalences of the modifying enzyme genes aac (6')-Ib, ant (3â³)-Ia, and aph (3')-I were 51·7, 81·7, and 58·3%, respectively, which are different from a previous study in which the occurrences of these genes were 3, 64, and 72%, respectively. Among the 40 isolates that were armA-positive, the prevalences of bla(TEM), bla(SHV), and bla(CTX-M-3) genes were detected for the first time in China, and their occurrences were 45, 65, and 52·5%, respectively. In all, A. baumannii with all the 16S rRNA methylase, modifying enzyme, and ESBL genes is extremely prevalent in northeastern Sichuan, China, posing a serious clinical concern with a major therapeutic threat in the future.
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Acinetobacter baumannii/genética , Metiltransferases/genética , RNA Ribossômico 16S/genética , beta-Lactamases/genética , Aminoglicosídeos/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , China , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Imipenem/farmacologia , Meropeném , Testes de Sensibilidade Microbiana/métodos , Tienamicinas/farmacologiaRESUMO
This study aims to investigate the regulative effects of microRNA-451a (miR-451a) on cell proliferation and sensitivity to tamoxifen in breast cancer cells. In cell culture experiments, the lentiviral vectors of pHBLV-miR-451a and pHBLV-miR-451a sponge were constructed and used to transfect MCF-7 and LCC2 cells. The transfection efficiency was tested by fluorescent observation, and cell lines with stable over- or downregulated expression of miR-451a were established. The expression of miR-451a and the target gene macrophage migration inhibitory factor (MIF) were detected by real-time reverse transcriptase polymerase chain reaction and/or western blot. Moreover, MTT assay, colony formation, and Transwell invasion assays were also performed. Data showed that the recombinant lentiviral vectors were constructed correctly, and the virus titer was 1 × 10(8) CFU/mL. The stable transfected cells were obtained. Overexpression of miR-451a downregulated MIF expression in mRNA and protein levels and inhibited cell proliferation, colony formation, and invasion of breast cancer cells. Downregulation of miR-451a upregulated MIF expression and increased breast cancer cell growth, invasion, and tamoxifen sensitivity. In summary, the miR-451a/MIF pathway may play important roles in the biological properties of breast cancer cells and may be a potential therapeutic target for breast cancer.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , MicroRNAs/metabolismo , Tamoxifeno/uso terapêutico , Sequência de Bases , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Oxirredutases Intramoleculares/genética , Lentivirus/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , MicroRNAs/genética , Dados de Sequência Molecular , Invasividade Neoplásica , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA , Tamoxifeno/farmacologia , Transdução Genética , Transfecção , Montagem de Vírus/efeitos dos fármacosRESUMO
OBJECTIVE: The abuse of antimicrobials is a serious concern in China. Several measures have been taken to improve the rational use of antimicrobials, including the establishment of a national surveillance network for antimicrobial use. This study describes the dynamic changes in antimicrobial use in China between 2001 and 2010, with the scope of identifying targets to improve the prescription of antimicrobials. METHODS: Five point prevalence surveys were performed in hospitals across mainland China in 2001, 2003, 2005, 2008, and 2010. All inpatients who were admitted for at least 24 hours were included in the study. Details regarding antimicrobial use by these patients and the collection of samples for bacterial culture from inpatients administered therapeutic antimicrobials were recorded. RESULTS: The surveys encompassed tertiary hospitals from all 31 provinces of mainland China. Antimicrobial use prevalence decreased from 54.79% in 2001 to 46.63% in 2010. While this decline was observed in most hospital departments, antimicrobial use remained stable or increased in others. Antimicrobial use prevalence was relatively high in the Pediatrics departments and general intensive care units, whereas it was lower in the Obstetrics (Neonatal group) departments in each survey. The proportion of patients administered a single antimicrobial increased from 60.78% in 2001 to 70.16% in 2010, while the proportion of administration of two or more antimicrobials declined. The bacterial culture rate increased from 25.22% in 2003 to 34.71% in 2010. Antimicrobial use prevalence (47.96% vs 46.16%), bacterial culture rate (36.40% vs 34.19%), and the proportion of administration of a single antimicrobial (71.41% vs 67.33%) were higher in teaching hospitals than in nonteaching hospitals in 2010. CONCLUSION: Although measures for enhancing the rational use of antimicrobials have been effective, further improvements are required. The findings from this study can promote such improvements.