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INTRODUCTION: Surgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis rates subsequent to incomplete or complete resection. Chemoradiotherapy has the potential to induce coronary artery occlusion, thereby potentially impacting patients' long-term survival rates. The existing literature currently lacks comprehensive research on the lesion characteristics of coronary artery injury resulting from chemoradiotherapy. CASE PRESENTATION: The male patient, aged 55, was admitted to the hospital due to recurrent chest tightness and pain persisting for one week. Notably, the patient had previously undergone curative resection surgery for thymic carcinoma seven years ago. After the surgical procedure, the patient underwent a course of adjuvant chemotherapy comprising docetaxel and platinum. 11 months later, imaging examination diagnosed tumor recurrence, and concurrent chemoradiotherapy was administered at a total dose of 62 Gy/31F for planning gross target volume (PGTV) and 54 Gy/31F for planning target volume (PTV) with 2 cycles of paclitaxel and cisplatin. Re-admission of the patient occurred after a 7-year interval subsequent to the completion of concurrent chemoradiotherapy, leading to a subsequent diagnosis of acute non-ST segment elevation myocardial infarction. Following administration of antiplatelet, anticoagulant, and anti-myocardial ischemia therapy, coronary angiography revealed the presence of a bifurcation lesion at the distal end of the left main trunk. Intravascular ultrasound (IVUS) examination demonstrated significant negative remodeling of both the main trunk and its branches at the bifurcation site, characterized by minimal atherosclerotic plaque components. CONCLUSIONS: Chemoradiotherapy may induce damage to endothelial cells, resulting in an inflammatory response. Negative remodeling of blood vessels is likely to occur, primarily characterized by vasoconstriction but with less atherosclerotic plaque burden. Routine stent implantation in negatively remodeled areas may lead to vascular rupture, necessitating intravascular imaging examination.
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Timoma , Neoplasias do Timo , Humanos , Masculino , Neoplasias do Timo/terapia , Neoplasias do Timo/diagnóstico por imagem , Pessoa de Meia-Idade , Resultado do Tratamento , Fatores de Tempo , Timoma/terapia , Timoma/diagnóstico por imagem , Angiografia Coronária , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/terapia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/lesões , Vasos Coronários/efeitos dos fármacos , Quimiorradioterapia/efeitos adversosRESUMO
Exosome is an important way for tumor cells to communicate with other cells and plays an important role in tumor progression. Previous studies revealed that miR-195-5p acts as a tumor suppressor in lung cancer. However, the role and molecular mechanism of exosomal transferred miR-195-5p in lung adenocarcinoma (LAC) remains unknown. Here, we found that miR-195-5p expression in circulating exosomes of LAC patients was lower than that of healthy controls. Meanwhile, the expression of exosomal miR-195-5p from normal bronchial epithelial cell line BEAS-2B cells was significantly higher than that of lung cancer cell lines. The exosome labeling assay confirmed that BEAS-2B cells-derived exosomes could be captured by lung cancer cells. Furthermore, exosomal miR-195-5p derived from BEAS-2B cells remarkably inhibited the proliferation, migration, invasion of lung cancer cells, and tumor growth in vivo. In addition, exosomal miR-195-5p from BEAS-2B cells also suppressed the tube-forming ability of vascular endothelial cells. Moreover, we verified that miR-195-5p decreased apelin (APLN) expression to inactivate the Wnt signaling pathway, thereby inhibiting tumor invasiveness and angiogenesis. In conclusion, our research shows that exosomal miR-195-5p from normal bronchial epithelial cells hinders the progression of LAC, suggesting that regulation of exosomal miR-195-5p provides a novel strategy for LAC treatment.
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Adenocarcinoma de Pulmão , Exossomos , Neoplasias Pulmonares , MicroRNAs , Humanos , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Células Endoteliais/patologia , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Background: Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods: This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30 mg as single dose, or 50 mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4 : 1 ratio. Results: 59 healthy volunteers received tenapanor 10 mg (n = 12 Chinese), 30 mg (n = 12 Chinese), or 50 mg (n = 12 (Chinese), n = 11 (Caucasian)) or placebo (n = 12, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50 mg) of Chinese subjects, the mean Cmax, AUC0-t, and AUC0-∞ of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The Cmax accumulation ratio was 1.55 to 6.92 after 50 mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50 mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion: Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.
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Síndrome do Intestino Irritável , Sulfonamidas , Humanos , Isoquinolinas/efeitos adversos , Isoquinolinas/farmacocinética , Área Sob a Curva , Método Duplo-Cego , Voluntários Saudáveis , China , Relação Dose-Resposta a DrogaRESUMO
The structure of spinal motion segments and spinal vasculature is complicated. Visualizing the three-dimensional (3D) structure of the spine may provide guidance for spine surgery. However, conventional imaging techniques fail to simultaneously obtain 3D images of soft and hard tissues, and achieving such coimaging states of the spine and its vascular networks remains a challenge. Synchrotron radiation micro-CT (SRµCT) provides a relatively effective and novel method of acquiring detailed 3D information. In this study, specimens of the thoracic spine were obtained from six mice. SRµCT was employed to acquire 3D images of the structure, and histologic staining was performed for comparisons with the SRµCT images. The whole spinal motion segments and the spinal vascular network were simultaneously explored at high resolution. The mean thickness of the cartilaginous end plates (CEPs) and the volume of the intervertebral discs (IVDs) were calculated. The surface of the CEPs and the facet joint cartilage (FJC) were presented as heat maps, which allowed for direct visualization of the thickness distribution. Regional division revealed heterogeneity among the ventral, central, and dorsal parts of the CEPs and between the superior and inferior parts of the facet processes. Moreover, the connections and spatial morphology of the spinal vascular network were visualized. Our study indicates that SRµCT imaging is an ideal method for high-resolution visualization and 3D morphometric analysis of the whole spinal motion segments and spinal vascular network.
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Disco Intervertebral , Articulação Zigapofisária , Animais , Imageamento Tridimensional/métodos , Camundongos , Síncrotrons , Microtomografia por Raio-X/métodosRESUMO
PURPOSE: To evaluate the potential ethnic differences of ferric pyrophosphate citrate (FPC, Triferic) in healthy subjects and patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) and identify covariates that may influence pharmacokinetics (PK) of FPC. METHODS: Data were collected from 2 Asian and 4 non-Asian clinical studies involving healthy subjects and CKD-5HD patients. Three population PK models were developed: M1 for intravenous (IV) administration of FPC in healthy subjects; M2 for dialysate administration of FPC in CKD-5HD patients; M3 for pre-dialyzer administration of FPC in CKD-5HD patients. All the models were fitted to concentration versus time data of FPC using the nonlinear mixed effect approach with the NONMEM® program. All statistical analyses were performed using SAS version 9.4. RESULTS: In total, 26 Asians and 65 non-Asians were included in the final model analysis database. Forty healthy subjects were administered FPC via intravenous (IV) route and 51 patients with CKD-5HD via dialysate (N = 50) and pre-dialyzer blood circuit administration (N = 51). The PK parameters of FPC IV were similar. The population PK model showed good parameter precision and reliability as shown by model evaluation, and no relevant influence of ethnicity on PK parameters was observed. In healthy subjects, the maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) decreased with increase in lean body mass (LBM) and the average serum total iron at 6 h before the baseline period (Feav), whereas, in both patient populations, Cmax and AUC decreased with increase in LBM and decrease in Febaseline. Other factors such as gender, age, Feav, and ethnicity had no influence on PK exposures in patients. The influence of LBM on PK exposures in patients was smaller than that in healthy subjects (ratio of AUC0-24 for the 5th [68 kg] and 95th [45 kg] patient's LBM was almost 1). The influence of Feav and LBM on PK exposures was < 50%. CONCLUSION: The population pharmacokinetics model successfully described the PK parameters of FPC in healthy subjects and CKD-5HD patients and were comparable between Asian and non-Asian populations.
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Hematínicos , Falência Renal Crônica , Citratos , Soluções para Diálise/uso terapêutico , Difosfatos , Etnicidade , Hematínicos/uso terapêutico , Humanos , Ferro , Falência Renal Crônica/tratamento farmacológico , Reprodutibilidade dos TestesRESUMO
Melanoma is characterized by high mortality and poor prognosis due to metastasis. AFF4 (AF4/FMR2 family member 4), as a scaffold protein, is a component of the super elongation complex (SEC), and is involved in the progression of tumors, e.g., leukemia, head and neck squamous cell carcinoma (HNSCC). However, few studies on AFF4 have focused on melanoma. Here, AFF4 expression levels and clinicopathological features were evaluated in melanoma tissue samples. Then, we performed cell proliferation, migration and invasion assays in A375 and A2058 cells lines in vitro to evaluate the role of AFF4 in melanoma. The effects of AFF4 knockdown in vivo were characterized via a xenograft mouse model. Finally, the correlation between c-Jun and AFF4 protein levels in melanoma was analyzed by rescue assay and immunohistochemistry (IHC). We found that AFF4 expression was upregulated in melanoma tumor tissues and that AFF4 protein expression was also closely related to the prognosis of patients with cutaneous melanoma. Moreover, AFF4 could promote the invasion and migration of melanoma cells by mediating epithelial to mesenchymal transition (EMT). AFF4 might regulate c-Jun activity to promote the invasion and migration of melanoma cells. Importantly, c-Jun was regulated by the AFF4 promoted melanoma tumorigenesis in vivo. Taken together, AFF4 may be a novel oncogene that promotes melanoma progression through regulation of c-Jun activity.
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Melanoma/patologia , Proteínas Proto-Oncogênicas c-jun/genética , Neoplasias Cutâneas/patologia , Fatores de Elongação da Transcrição/fisiologia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Proto-Oncogênicas c-jun/metabolismo , Neoplasias Cutâneas/genéticaRESUMO
PURPOSE: To compare the efficacy of single anterior and single posterior approach of debridement, interbody fusion, and fixation for the treatment of mono-segment lumbar spine tuberculosis (TB) patients. METHODS: Eighty-seven patients with mono-segment lumbar TB who underwent debridement, interbody fusion, and fixation through either single anterior (Group A) or single posterior approach (Group B) from January 2007 to January 2017 were enrolled in this study. The duration of the operation, blood loss, complication rate, visual analog scale (VAS), Oswestry disability index (ODI), Frankel scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), kyphosis angle, correction rate, correction loss, and time taken for bone graft fusion were compared between the groups. RESULTS: The average period of follow-up was 34.3 ± 9.5 months (24-56 months). No significant differences were observed between patients in Group A and patients in Group B in terms of gender, age, body mass index (BMI), duration of illness and preoperative evaluative indices (P > 0.05). The mean operation time and blood loss was significantly higher in Group A (P = 0.000), along with a slightly higher rate of complications compared with Group B (P = 0.848). The VAS, ODI and Frankel scale scores showed significant improvement in both groups (P = 0.000), along with the ESR, CRP and kyphosis indices (P = 0.000), which were similar in both groups at the final follow-up. CONCLUSION: Both single anterior and single posterior approaches of debridement, interbody fusion and fixation are effective for mono-segment lumbar TB patients, although the single posterior approach is of a shorter duration and results in less blood loss.
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Cifose , Fusão Vertebral , Tuberculose da Coluna Vertebral , Humanos , Desbridamento/métodos , Fusão Vertebral/métodos , Vértebras Torácicas/cirurgia , Proteína C-Reativa , Resultado do Tratamento , Estudos Retrospectivos , Tuberculose da Coluna Vertebral/cirurgia , Vértebras Lombares/cirurgiaRESUMO
Coinfections with the tick-borne pathogens Theileria luwenshuni and Anaplasma phagocytophilum can cause significant economic losses in sheep and goat farming. The difficulty in detecting these two pathogens by microscopic examination warrants the development of a rapid detection test to discriminate them. In this study, a duplex polymerase chain reaction (PCR) assay was developed to simultaneously detect T. luwenshuni and A. phagocytophilum. Alignment of the sequences from related pathogens allowed us to design a primer pair targeting the 18S ribosomal RNA gene in T. luwenshuni and generate a target product of 962 bp, whereas a previously reported species-specific primer (SSAP2f/SSAP2r) for A. phagocytophilum was used in the same reaction to generate a product of 641 bp. Genomic DNA from T. luwenshuni and A. phagocytophilum was 10-fold serially diluted for testing PCR sensitivity. Under the optimal PCR conditions we established, the lower limit of detection of the assay was 29.13 fg/µL for T. luwenshuni and 1.53 fg/µL for A. phagocytophilum, and PCR primers used in this study were confirmed to be 100% species-specific using other hemoparasites previously identified by other methods. No significant difference was found between conventional and duplex PCR protocols used to detect the two species. Our study provides an effective, sensitive, specific, and accurate tool for the diagnosis and epidemiological surveillance of mixed infections of the two pathogens in sheep and goats.
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Anaplasma phagocytophilum , Doenças das Cabras , Doenças dos Ovinos , Theileria , Anaplasma/genética , Anaplasma phagocytophilum/genética , Animais , Doenças das Cabras/diagnóstico , Cabras , Reação em Cadeia da Polimerase/veterinária , Sensibilidade e Especificidade , Ovinos , Doenças dos Ovinos/diagnóstico , Theileria/genéticaRESUMO
BACKGROUND: Family caregivers of elderly patients with spinal tumours experience considerable pain and burden during the care process. This study aims to investigate the factors associated with caregiver burden in family caregivers of elderly patients with spinal tumours. METHODS: A total of 220 elderly patients with spinal tumours (age ≥ 65 years) hospitalized at the spine centre of our hospital from January 2015 to December 2017 and their family caregivers were recruited for this cross-sectional study. All participants completed a sociodemographic questionnaire. Caregiver burden, social support and self-efficacy were assessed by the Chinese version of the Zarit Burden Interview (ZBI), the Social Support Rating Scale (SSRS) and the General Self-Efficacy Scale (GSE), respectively. The factors related to caregiver burden were analysed by multivariate analysis. P < 0.05 was considered statistically significant. RESULTS: The 216 elderly patients with spinal tumours were 71.59 ± 8.49 years old, and their caregivers were 70.46 ± 9.13 years old. A total of 170 patients were cared for by their spouses, who accounted for 78.7% of all caregivers. The ZBI score for the family caregivers was 35.5 ± 7.5, and most caregivers (84.5%) reported a moderate or heavy burden. The factors related to caregiver burden included patient paralysis, the primary cancer site, chemotherapy and/or radiation, cognitive dysfunction, functional status, monthly income, pain score, caregivers' SSRS score, and GSE score. CONCLUSIONS: Most family caregivers of elderly patients with spinal tumours have a considerable caregiver burden. Interventions based on social support and self-efficacy can help reduce caregiver burden.
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Cuidadores/psicologia , Efeitos Psicossociais da Doença , Neoplasias da Coluna Vertebral , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , China , Estudos Transversais , Feminino , Humanos , Masculino , Análise Multivariada , Apoio Social , Inquéritos e QuestionáriosRESUMO
PURPOSE: To compare the efficacy of conventional interlaminar fenestration discectomy (IFD) with transforaminal endoscopic lumbar discectomy (TELD) for treating lumbar disc herniation (LDH). METHODS: The clinical data of 1100 patients who had been diagnosed with LDH between January 2012 and December 2017 were retrospectively analysed. IFD was performed on 605 patients in Group A, whereas TELD was performed on 505 patients in Group B. The Oswestry Disability Index, Visual Analogue Scale for pain and modified MacNab criteria were used to evaluate the outcomes. The surgery duration, intraoperative blood loss, postoperative off-bed activity and postoperative length of hospital stay were recorded. RESULTS: The follow-up period ranged from 24 to 60 months, with an average of 43 months. The excellent and good outcome rates were 93.5% in Group A and 92.6% in Group B. There was no significant difference in efficacy between the groups (P > 0.05). However, Group B had significantly less intraoperative blood loss and shorter bed rest duration and postoperative length of hospital stay than Group A (P < 0.05). There were two cases of postoperative recurrence in Group A and three in Group B. CONCLUSIONS: Although conventional IFD and TELD had similar levels of efficacy in treating LDH, TELD had several advantages. There was less intraoperative bleeding, shorter length of hospital stay and shorter bed rest duration. It can be considered a safe and effective surgical option for treating LDH.
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Discotomia Percutânea , Deslocamento do Disco Intervertebral , Discotomia/efeitos adversos , Endoscopia , Seguimentos , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Capsular contracture, mainly caused by Staphylococcus epidermidis (S. epidermidis) biofilm formation, is a complex problem for breast cancer patients who undergo surgical prosthetic breast reconstruction. Estradiol has been reported to be involved in the formation of bacterial biofilms. Thus, the underlying mechanism of estradiol in capsular contracture needs to be investigated. METHODS: Biofilm-related gene expressions were measured by qRT-PCR after sterilizing the silicone with bacterial suspension and E2 treatment in vitro. Rat models were established with bilateral ovariectomy operations and estradiol subcutaneous injections. The effects of estradiol on capsular contracture were detected by monitoring serum estradiol levels, bacterial infection rate in organs, biofilm formation and capsular contracture in vivo; inflammatory factors in vivo were examined as well. Biofilm on the silicone implants was observed under a scanning electron microscope. RESULTS: Both positive regulatory genes and negative regulatory genes were increased by the high concentration of estradiol, suggesting that estradiol can promote the formation of biofilm by not only positive but also negative regulations. High estradiol levels increased bacterial infection rate in organs, biofilm formation and capsular contracture. Further, high estradiol caused a large number of inflammatory cells to infiltrate and caused serious inflammatory reactions that aggravate the immune imbalances of the host. CONCLUSION: High estradiol levels contribute to increasing capsular contracture caused by S. epidermidis biofilm formation. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Implantes de Mama , Mamoplastia , Animais , Implantes de Mama/efeitos adversos , Estradiol , Feminino , Humanos , Mamoplastia/efeitos adversos , Ratos , Silicones , Staphylococcus epidermidisRESUMO
BACKGROUND: Cancer associated fibroblasts (CAFs) are known to be crucial constituents of cancer microenvironment (CME) and play an important role in initiation, progression and metastasis of various types of cancer, such as oral cancer, pancreatic cancer, and gastric cancer. CAFs are usually derived from normal fibroblasts (NFs), but the mechanism of the transition in gastric cancer has not yet been fully elucidated. METHODS: qRT-PCR and western blot were employed to investigate differences of miR-141 and STAT4 expression respectively. The CAF-like features and wnt/ß-catenin pathway related proteins in NF or BMSC were assessed by qRT-PCR or western blot after treated with the conditioned medium from different indicated groups of gastric cancer cells. The invasion and migration ability of AGS cells after transfection were analyzed by Transwell assay and wound healing assay. Dual-luciferase report assay was employed to determine the direct binding of miR-141 to STAT4 3' UTR. RESULTS: For the first time, the present study found that STAT4 over-expression in gastric cancer cells induced NFs to obtain CAF-like features via activating wnt/ß-catenin pathway. Further gain-of-function and loss-of-function analysis revealed that miR-141 not only limited the migration and invasion of the gastric cancer cells, but also inhibited the transition of NFs and BMSC to CAFs. The luciferase assay indicated that miR-141 directly targeted the 3'-UTR predictive sequence of STAT4. CONCLUSION: Our data showed that miR-141 inhibited migration and invasion of gastric cancer cells and inhibited transition from NFs to CAFs via targeting STAT4/wnt/ß-catenin pathway.
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Fibroblastos Associados a Câncer/patologia , Fibroblastos/patologia , MicroRNAs/genética , Fator de Transcrição STAT4/metabolismo , Neoplasias Gástricas/patologia , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Humanos , Células-Tronco Mesenquimais/patologia , Invasividade Neoplásica/patologia , Microambiente Tumoral/fisiologiaRESUMO
BACKGROUND/AIM: MiR-125b plays an important role in breast cancer. The current study was to explore the expression and function of miR-125b in triple negative breast cancer cells. MATERIALS AND METHODS: The expression of miR-125b in human TNBC samples and cell lines were examined by qRT-PCR. MTT, scratch assays and transwell assays were utilized to observe the proliferation, migration and invasion ability. MiR-125b's target gene and downstream signaling pathways were investigated by Luciferase Reporter Assays, qRT-PCR, immunofluorescence assays and western bolt. RESULTS: MiR-125b was highly expressed in human TNBC tissues and cell lines. Inhibiting miR-125b expression suppressed the proliferation, cell migration and invasion. The three-prime untranslated region (3´-UTR) of adenomatous polyposis coli (APC) mRNA contains miR-125b binding sites, and inhibiting miR-125b expression suppressed the activity of the intracellular Wnt/ß-catenin pathways and EMT. CONCLUSION: Inhibiting miR-125b regulates the Wnt/ß-catenin pathway and EMT to suppress the proliferation and migration of MDA-MB-468 TNBC cells.
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Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , MicroRNAs/fisiologia , Metástase Neoplásica/genética , Neoplasias de Mama Triplo Negativas/patologia , Via de Sinalização Wnt/genética , beta Catenina/metabolismo , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Feminino , Genes APC , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Regulação para CimaRESUMO
Anaplasma phagocytophilum, the bacterial pathogen responsible for tick-borne fever and human granulocytic anaplasmosis, can seriously affect the health of humans and a wide range of other mammals. In this study, we developed a recombinase polymerase amplification (RPA) assay to detect A. phagocytophilum in clinical samples. Following alignment of the relevant DNA sequences, a pair of specific primers based on the 16S rRNA gene was designed to specifically detect A. phagocytophilum. The assay was performed at a constant temperature of 38⯰C for 30â¯min, with a final primer concentration of 0.4⯵M. The specificity of the primers was confirmed when DNA from A. phagocytophilum was used as the positive control, and DNA from other related pathogens were used as the negative controls, with ddH2O acting as the blank control. The results showed that the primers did not cross-react with DNA from the other related pathogens. The assay's detection limit was 1.77â¯×â¯10-5â¯ng/µl, a 10â¯×â¯higher sensitivity level than that determined for nested PCR. The RPA assay's performance was evaluated using 44 clinical samples, and the prevalence results for A. phagocytophilum were found to not differ significantly between the RPA assay and the nested PCR. Thus, we have developed a specific, sensitive, rapid and cost-effective RPA method, requiring only a water bath, for the detection of A. phagocytophilum. The assay should be especially useful in resource-limited areas where access to laboratory equipment is limited.
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Anaplasma phagocytophilum/isolamento & purificação , Ehrlichiose/veterinária , Reação em Cadeia da Polimerase/veterinária , Doenças dos Ovinos/microbiologia , Anaplasma phagocytophilum/genética , Animais , Análise Custo-Benefício , DNA Bacteriano/sangue , DNA Bacteriano/química , DNA Bacteriano/isolamento & purificação , DNA Polimerase Dirigida por DNA , Ehrlichiose/diagnóstico , Ehrlichiose/microbiologia , Sistemas Automatizados de Assistência Junto ao Leito/economia , Sistemas Automatizados de Assistência Junto ao Leito/normas , Reação em Cadeia da Polimerase/economia , Reação em Cadeia da Polimerase/normas , RNA Ribossômico 16S/genética , Recombinases , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ovinos , Doenças dos Ovinos/diagnóstico , Fatores de TempoRESUMO
BACKGROUND: In Xuan Wei, China, the lung cancer mortality rate is rising significantly more than that of the nation overall. However, it remains unclear 1) if improved diagnosis can just partially explain this observation and how other local risk factors may be correlated with the lung cancer mortality rate and 2) how the lung cancer mortality rates differ within Xuan Wei and how these spatiotemporal patterns are linked with local risk factors. To increase etiological knowledge, this study evaluated the spatial and temporal distributions of the health effects (the lung cancer mortality rates) from 2011 to 2015. METHODS: Four steps of spatial analysis were applied, as follows: 1) hotspot analysis to determine the geographical patterns of lung cancer mortality, 2) spatially-weighted sum to identify areas with higher health risks, 3) bivariate statistical analysis to assess the overall correlation between coal mines and lung cancer mortality, and 4) geographically-weighted regression to test for correlations among different towns within Xuan Wei. RESULTS: Women had higher lung cancer mortality rates than those in men, with an increasing trend in both sexes over time. The incidence rates in Laibin Town were the highest in Xuan Wei every year. Over the 5-year study period, the lung cancer mortality was increasingly concentrated in Laibin, Shuanglong, and Longchang, where the smoky coal mines are most concentrated. The population-level health risks from the coal mine in Xuan Wei were mapped and divided into five types of risk areas (Type I - Type IV). Correlation analysis revealed that there was no significant correlation between lung cancer mortality as a whole and coal mine distribution during the 5-year study period. However, the geographically-weighted regression revealed a stronger correlation in medium (Type III) and second-lowest (Type IV) health risks. CONCLUSIONS: Xuan Wei lung cancer mortality has increased continuously since the third national retrospective surveys on the causes of death by the Ministry of Health of the People's Republic of China (2004-2005), especially for local women and residents over 35 years of age. Geographically, lung cancer in Xuan Wei showed unique spatiotemporal clustering. The local lung cancer mortality was significantly correlated with the smoky coal mine geographically. Some specific towns (Laibin, Shuanglong, and Longchang) within Xuan Wei manifested high correlations between lung cancer mortality and coal mines. The effects of coal mines on lung cancer mortality rates also spread geographically outward from these areas. Public health concern regarding lung cancer in Xuan Wei should prioritize higher-risk towns surrounded by smoking coal mines. Intervention strategies for particular toxic coal types require further studies on their chemical characteristics and mechanisms of carcinogenesis. Additional studies are also warranted to systematically examine the local environmental health risks related to coal industries and combustion air pollution and eventually to conduct early screening of lung cancer for local people who are more exposed to smoky coal in high-risk areas.
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Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise Espaço-TemporalRESUMO
In this study, we attempted to find out the underlying mechanism of Benzoapyrene and metastasis of lung cancer cells. We also did experiments to testify the connection between BaP and its potential target, TNF-α. Cell median lethal dose (IC50 ) of both cells was measured by crystal violet method. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot were employed to detect the expression of TNF-α. Wound healing assay and transwell assay were utilized to testify the impacts of BaP and TNF-α on the metastasis of lung cancer cells. Cell death rate was elevated with the increase of BaP concentration. BaP increased the number of metastatic cells of lung cancer. The expressions of TNF-α pathway-associated protein (TNF-α, NF-kB [P65], Caspase3, and Caspase8) were enhanced by overexpressed BaP. TNF-α shRNA suppressed the positive effects of BaP on migration and invasion of lung cancer cells. Our study validated the positive effects of BaP on the metastasis of lung cancer cells. We also revealed the instrumental role of TNF-α in helping the development of lung cancer cells induced by BaP.
Assuntos
Benzopirenos/toxicidade , Movimento Celular/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Células A549 , Humanos , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismoRESUMO
Understanding the three-dimensional ultrastructure morphology of tendon-to-bone interface may allow the development of effective therapeutic interventions for enhanced interface healing. This study aims to assess the feasibility of propagation phase-contrast synchrotron radiation microtomography (PPC-SRµCT) for three-dimensional characterization of the microstructure in rabbit patella-patellar tendon interface (PPTI). Based on phase retrieval for PPC-SRµCT imaging, this technique is capable of visualizing the three-dimensional internal architecture of PPTI at a cellular high spatial resolution including bone and tendon, especially the chondrocytes lacuna at the fibrocartilage layer. The features on the PPC-SRµCT image of the PPTI are similar to those of a histological section using Safranin-O staining/fast green staining. The three-dimensional microstructure in the rabbit patella-patellar tendon interface and the spatial distributions of the chondrocytes lacuna and their quantification volumetric data are displayed. Furthermore, a color-coding map differentiating cell lacuna in terms of connecting beads is presented after the chondrocytes cell lacuna was extracted. This provides a more in-depth insight into the microstructure of the PPTI on a new scale, particularly the cell lacuna arrangement at the fibrocartilage layer. PPC-SRµCT techniques provide important complementary information to the conventional histological method for characterizing the microstructure of the PPTI, and may facilitate in investigations of the repair mechanism of the PPTI after injury and in evaluating the efficacy of a different therapy.
Assuntos
Imageamento Tridimensional/métodos , Patela/diagnóstico por imagem , Ligamento Patelar/diagnóstico por imagem , Microtomografia por Raio-X/métodos , Animais , Estudos de Viabilidade , Feminino , Coelhos , SíncrotronsRESUMO
Chemotherapy on gliomas is not satisfactorily efficient because the presence of blood-brain barriers (BBB) leads to inadequate exposure of tumor cells to administered drugs. In order to facilitate chemotherapeutics to penetrate BBB and increase the treatment efficacy of gliomas, electromagnetic pulse (EMP) was applied and the 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU) lomustine concentration in tumor tissue, tumor size, tumor apoptosis, and side effects were measured in glioma-bearing rat model. The results showed that EMP exposure could enhance the delivery of CCNU to tumor tissue, facilitate tumor apoptosis, and inhibit tumor growth without obvious side effects. The data indicated that EMP-induced BBB disruption could enhance delivery of CCNU to glioblastoma multiforme and increase treatment efficacy in glioma-bearing rats. Bioelectromagnetics. 39:60-67, 2018. © 2017 Wiley Periodicals, Inc.
Assuntos
Antineoplásicos/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos da radiação , Sistemas de Liberação de Medicamentos/métodos , Fenômenos Eletromagnéticos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Glioblastoma/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: To evaluate synchrotron radiation-based Fourier transform infrared microspectroscopy (SR-FTIR) as a tool for quantitative mapping of the content and distribution of the extracellular matrix in decellularized fibrocartilage bioscaffolds, and to provide a new platform for quantitatively characterizing bioscaffolds for tissue engineering. METHODS: Fibrocartilage was harvested and cut into book-shape bioscaffolds (N = 54), which were then decellularized. The structures and distribution of collagen fibrous and intrinsic ultrastructure in decellularized fibrocartilage bioscaffolds were evaluated by histological staining and scanning electron microscopy (SEM), respectively. The content of collagen and proteoglycan in the cellularized or decellularized bioscaffolds were also measured by SR-FTIR and biochemical assay. RESULTS: Book-shape fibrocartilage decellularized bioscaffolds were successfully obtained. Histological examination revealed that the structure of extracellular matrix endured during decellularization. Histology and DNA quantification analysis confirmed substantial removal of cells during decellularization. SEM demonstrated that intrinsic ultrastructure of the fibrocartilage bioscaffold was also well preserved. SR-FTIR quantitative analysis confirmed that decellularization had a significant effect on the content and distribution of collagen and proteoglycan in fibrocartilage bioscaffolds, these results are confirmed with the biochemical assay results. CONCLUSION: SR-FTIR imaging can capture the histological morphology of decellularized bioscaffolds. Moreover, it can be used for quantitative mapping of the content and distribution of collagen in the bioscaffolds.
Assuntos
Matriz Extracelular , Fibrocartilagem/citologia , Síncrotrons , Alicerces Teciduais , Animais , Matriz Extracelular/metabolismo , Feminino , Fibrocartilagem/metabolismo , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Engenharia Tecidual/métodosRESUMO
BACKGROUND: To compare the clinical efficacy of single posterior debridement, bone grafting and instrumentation with that of single-stage anterior debridement, bone grafting and posterior instrumentation for treatment of adult patients with thoracic and thoracolumbar spinal tuberculosis (TB). METHODS: We performed a retrospective analysis of 64 adult patients with thoracic and thoracolumbar spinal TB who underwent surgery between January 2011 and December 2014. Of the 64 patients, 34 patients were treated using a single posterior-only approach (posterior debridement, bone grafting and instrumentation; Group A). Thirty patients were treated with a combined anterior and posterior approach (single-stage anterior debridement, bone grafting and posterior instrumentation; Group B). Clinical manifestations, laboratory and imaging results were subjected to statistical analysis. RESULTS: The mean (±standard deviation) duration of follow-up was 16.8 ± 1.4 months (range, 10-34). Bony fusion was achieved in all the bone grafts with no loosening or breakage of internal fixation. In both of the groups, the visual analog scale (VAS) pain score, ESR and CRP at 6 weeks after operation and at the most recent follow-up were significantly lower than the preoperative level (p < 0.05). The operation time, intraoperative blood loss and length of hospital stay in group A were significantly less than those in group B (P < 0.05). As of most recent follow-up, no significant between-group difference was observed with respect to the American Spinal Injury Association classification status (p > 0.05). Furthermore, no significant between-group difference was observed with respect to preoperative kyphosis angle, and postoperative angle correction and angle correction rate (P > 0.05). One patient in group A relapsed 20 months after operation, and was successfully treated with debridement using the combined anterior and posterior approach. CONCLUSION: Single posterior debridement, bone grafting and instrumentation for treatment of thoracic and thoracolumbar spinal TB can achieve similar curative effect as that with single-stage anterior debridement, bone grafting and posterior instrumentation, and is associated with additional advantages of shorter operation time, less bleeding and shorter length of hospital stay.