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Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase (RTK) primarily expressed in hematopoietic stem cells and dendritic cells (DCs). While FLT3 plays a critical role in the proliferation, development and maintenance of DCs, thus influencing immune responses under both normal and pathological conditions, there also exists some evidence that FLT3+DC may be involved with immune responses in liver transplantation (LT). In this study, results from single-cell sequencing data analysis revealed a clear relationship between FLT3+DCs and Regulatory T cells (Tregs) in liver tissue of LT recipients. In peripheral blood samples of LT patients, levels of FLT3+DCs were decreased post-LT-surgery, while Tregs were increased. In a LT mouse model, levels of FLT3+DCs in the liver and bone marrow exhibited an initial time-dependent decrease followed by an increase after LT surgery. Results as obtained with co-culture experiments using mature BMDCs and CD4+ T cells revealed fluctuations in Tregs in response to FLT3 inhibitors and the FLT3 ligand. These findings suggest that FLT3+DCs could emerge as a novel target for mitigating immune rejection in LT.
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Células Dendríticas , Rejeição de Enxerto , Transplante de Fígado , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores , Tirosina Quinase 3 Semelhante a fms , Linfócitos T Reguladores/imunologia , Animais , Células Dendríticas/imunologia , Tirosina Quinase 3 Semelhante a fms/metabolismo , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Masculino , Camundongos , Fígado/imunologia , Feminino , Técnicas de Cocultura , Pessoa de Meia-Idade , Células Cultivadas , Camundongos Endogâmicos BALB C , Proteínas de MembranaRESUMO
Regulation of tumor vessels has become one of the most common strategies for clinical anti-tumor therapy. In recent years, studies have found that the anti-tumor effect of limotherapy, which routinely inhibits tumor angiogenesis, is not ideal and may even deteriorate the tumor microenvironment, causing tumor resistance and distal metastasis and increasing the risk of tumor metastasis and recurrence. However, the proper use of anti-angiogenic drugs can promote the normalization of tumor vessels, improve the structure and function of tumor vessels, increase the number of functional vessels in the tumor, and reduce the number of ineffective vessels. It is beneficial to promote the penetration of anti-tumor drugs into the tumor, improve the microenvironment of tumor hypoxia and immunosuppression, and enhance the anti-tumor effect. Traditional Chinese medicine(TCM) has a long history of understanding the etiology and pathogenesis of tumors and has accumulated rich experience in tumor treatment, with significant clinical advantages and broad application prospects. In this study, from the perspective of bidirectional "soothing" or "blockage" regulation of tumor vessels, the commonly used molecular targets were sorted out, and the research status of anti-tumor regulation of tumor vessels by monomer-single herb-compound(herb pair) of TCM in recent years was summarized. The research on the anti-tumor effects of TCM compounds and active ingredients by regulating tumor vessels combined with other therapies was analyzed and sorted out, so as to provide ideas for the clinical application of TCM in regulating functions and anti-tumor effects of tumor vessels.
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Medicamentos de Ervas Chinesas , Neoplasias , Humanos , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Microambiente TumoralRESUMO
Skeletal muscle atrophy is a frequent complication after spinal cord injury (SCI) and can influence the recovery of motor function and metabolism in affected patients. Delaying skeletal muscle atrophy can promote functional recovery in SCI rats. In the present study, we investigated whether a combination of body weight support treadmill training (BWSTT) and glycine and N-acetylcysteine (GlyNAC) could exert neuroprotective effects, promote motor function recovery, and delay skeletal muscle atrophy in rats with SCI, and we assessed the therapeutic effects of the double intervention from both a structural and functional viewpoint. We found that, after SCI, rats given GlyNAC alone showed an improvement in Basso-Beattie-Bresnahan (BBB) scores, gait symmetry, and results in the open field test, indicative of improved motor function, while GlyNAC combined with BWSTT was more effective than either treatment alone at ameliorating voluntary motor function in injured rats. Meanwhile, the results of the skeletal muscle myofiber cross-sectional area (CSA), hindlimb grip strength, and acetylcholinesterase (AChE) immunostaining analysis demonstrated that GlyNAC improved the structure and function of the skeletal muscle in rats with SCI and delayed the atrophication of skeletal muscle.
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Acetilcisteína , Traumatismos da Medula Espinal , Humanos , Ratos , Animais , Acetilcisteína/metabolismo , Ratos Sprague-Dawley , Acetilcolinesterase/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Peso Corporal , Recuperação de Função Fisiológica/fisiologiaRESUMO
BACKGROUND: Zollinger-Ellison syndrome (ZES) results from hypersecretion of gastrin from pancreatic or duodenal neuroendocrine tumors, commonly referred to as gastrinomas. The high levels of gastrin lead to a typical presentation involving watery diarrhea and multiple ulcers in the duodenum. Here, we have presented the rare case of a patient with ZES and absence of hypergastrinemia as well as an atypical location of gastrinoma. CASE SUMMARY: A 72-year-old woman presented with the typical clinical manifestations of ZES, including upper abdominal pain, significant watery diarrhea, and acidic liquid vomitus. Surprisingly, however, she did not have an increased level of serum gastrin. In addition, there was no evidence of gastrinoma or any other ulcerogenic tumor. Esophagogastroduodenoscopy was conducted to examine the upper digestive tract. Revised diagnoses were considered, and an individualized treatment plan was developed. The patient responded to antacid medication while experiencing intermittent, recurring bouts of ZES. 18F-AlF-NOTA-octreotide positron emission tomography (18F-OC PET)/computed tomography (CT) helped locate the tumor. Postoperative pathology and immunohistochemistry results suggested that the tumor was a gastrinoma located at an unconventional site. CONCLUSION: This present case study demonstrates the possibility of ZES-like manifestation in patients with absence of hypergastrinemia. 18F-OC PET/CT is a relatively new imaging technique that can be applied for diagnosing even tiny gastrinomas that are atypical in terms of location.
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This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.
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Antineoplásicos , Produtos Biológicos , Animais , Camundongos , Cromatografia Líquida de Alta Pressão , Ciclo-Oxigenase 2 , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológicoRESUMO
The most frequent operation for anterior shoulder instability is the arthroscopic Bankart repair, which has a positive outcome and a low rate of complications. A variety of restoration procedures have been reported to reconstruct labral height and reproduce a dynamic concavity-compression reaction. The longitude-latitude loop is a knotless high-strength suture method that simultaneously tightens the joint capsule in the warp and weft direction and resists tearing. The suture method is safe and reproducible. This study aimed to present a longitude-latitude loop suture for joint capsule labral complex repair during Bankart arthroscopy surgery.
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Hepatic ischemia-reperfusion injury (IRI) is an adverse consequence of hepatectomy or liver transplantation. Recently, immune mechanisms involved in hepatic IRI have attracted increased attention of investigators working in this area. In specific, group 2 innate lymphoid cells (ILC2s), have been strongly implicated in mediating type 2 inflammation. However, their immune mechanisms as involved with hepatic IRI remain unclear. Here, we reported that the population of ILC2s is increased with the development of hepatic IRI as shown in a mouse model in initial stage. Moreover, M2 type CD45+CD11b+F4/80high macrophages increased and reached maximal levels at 24 h followed by a significant elevation in IL-4 levels. We injected exogenous IL-33 into the tail vein of mice as a mean to stimulate ILC2s production. This stimulation of ILC2s resulted in a protective effect upon hepatic IRI along with an increase in M2 type CD45+CD11b+F4/80high macrophages. In contrast, depletion of ILC2s as achieved with use of an anti-CD90.2 antibody substantially abolished this protective effect of exogenous IL-33 and M2 type CD45+CD11b+F4/80high macrophage polarization in hepatic IRI. Therefore, this exogenous IL-33 induced potentiation of ILC2s appears to regulate the polarization of CD45+CD11b+F4/80high macrophages to alleviate IRI. Such findings provide the foundation for the development of new targets and strategies in the treatment of hepatic IRI.
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Interleucina-33 , Hepatopatias , Fígado , Macrófagos , Traumatismo por Reperfusão , Animais , Imunidade Inata , Interleucina-33/farmacologia , Fígado/irrigação sanguínea , Fígado/imunologia , Hepatopatias/imunologia , Linfócitos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/imunologiaRESUMO
BACKGROUND: Mechanical loading has been widely considered to be essential for growth plate to maintain metabolism and development. Cyclic mechanical strain has been demonstrated to induce autophagy, whereas the relationship between cyclic tensile strain (CTS) and autophagy in growth plate chondrocytes (GPCs) is not clear. The objective of this study was to investigate whether CTS can regulate autophagy in GPCs in vitro and explore the potential mechanisms of this regulation. METHODS: The 2-week-old Sprague-Dawley rat GPCs were subjected to CTS of varying magnitude and duration at a frequency of 2.0 Hz. The mRNA levels of autophagy-related genes were measured by RT-qPCR. The autophagy in GPCs was verified by transmission electron microscopy (TME), immunofluorescence and Western blotting. The fluorescence-activated cell sorting (FACS) was employed to detect the percentage of apoptotic and necrotic cells. RESULTS: In GPCs, CTS significantly increased the mRNA and protein levels of autophagy-related genes, such as LC3, ULK1, ATG5 and BECN1 in a magnitude- and time-dependent manner. There was no significant difference in the proportion of apoptotic and necrotic cells between control group and CTS group. The autophagy inhibitors, 3-methyladenine (3MA) and chloroquine (CQ) reversed the CTS-induced autophagy via promoting the formation of autophagosomes. Cytochalasin D (cytoD), an inhibitor of G-actin polymerization into F-actin, could effectively block the CTS-induced autophagy in GPCs. CONCLUSION: Cyclic mechanical strain with high-tensile triggers autophagy in GPCs, which can be suppressed by 3MA and CQ, and cytoskeletal F-actin microfilaments organization plays a key role in chondrocytes' response to mechanical loading.
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Condrócitos , Lâmina de Crescimento , Animais , Autofagia , Condrócitos/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse MecânicoRESUMO
In this study, we introduce an arthroscopic technique for posterior-superior capsular fenestration and spinoglenoid cyst resection completely via a trans-rotator cuff approach. This approach can provide a full field of view and allow evaluation of the scope of the cyst under direct vision, which reduces the risk of recurrence and injury to the suprascapular neurovascular bundle.
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As one of the most common pathological changes in trauma and surgery practice, intestinal ischemia-reperfusion (I/R) injury is regarded as a major precipitating factor in the occurrence and development of fatal diseases. BRCA1-BRCA2-containing complex subunit 36 (BRCC36), a deubiquitinase, has been proved important in a variety of pathophysiological processes such as DNA repair, cell cycle regulation, tumorigenesis, and inflammatory response. However, the effect of BRCC36 on intestinal mucosal barrier injury after I/R has not been fully elucidated. Our research found that BRCC36 aggravated intestinal mucosal barrier injury caused by bone morphogenetic protein 2 after I/R by downregulating peroxisome proliferator-activated receptor-γ (PPARγ) signaling. These results suggested that BRCC36/PPARγ axis might serve as a potential therapeutic target for preventing intestinal mucosal barrier injury after I/R.
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PPAR gamaRESUMO
OBJECTIVE: To evaluate the outcomes of locked posterior shoulder dislocation with reverse Hill-Sachs lesions in patients treated with anatomical reconstructions. METHODS: Patients who were treated at our institution between January 2016 and June 2020 were retrospectively reviewed. The demographics of the patients including gender, age, occupation, and dominant arm were recorded. Eleven cases from 10 patients qualified in this study. Nine males and one female were included. The mean age of the patients was 44.8 years (range, 33-54 years). Mechanism of injury, duration between injuries and definitive diagnosis, misdiagnosis, size of humeral head impaction, treatment maneuver, and details of operation performed were reviewed. Plain radiographs and computed tomography (CT) scan were taken to determine the size of defects preoperatively and fracture healing during follow-up. During surgery, the deltopectoral approach was employed. Anatomical reconstruction procedure including reduction, disimpaction, bone grafting, and fixation were sequentially performed. Either cancellous autograft from iliac crest or allograft were used and the fractures were anatomically reduced and stabilized by screws or plates. Visual Analog Scale (VAS) and Constant-Murley score were recorded to determine the functional outcomes preoperatively, at 3 months and 6 months postoperatively, and at the last follow-up. The range of motion in forward flexion was recorded at 6 months follow-up postoperatively. RESULTS: Causes of injuries included epileptic seizure in four cases, fall in three cases, and road traffic accident in three cases. Misdiagnoses occurred in five out of 10 patients. The mean time between injury and definitive treatment among those misdiagnosed was 112 days. The mean size of the impacted reverse Hill-Sachs lesions was 33.95% (range, 19.1%-42.6%). All patients received surgical management with anatomical reconstruction approach, including open reduction, disimpaction, bone grafting, and internal fixation. The mean amount of bleeding during operation was 450 mL. The mean follow-up period was 22.6 months. Fracture healing was observed by 8 weeks in all cases postoperatively and evidence of bone grafting could not be further detected on CT scan at 6 month during follow-up. VAS was significantly lower at the last follow-up (0.68 ± 0.21) in comparison to preoperative scores (4.96 ± 0.97) (P < 0.05). Constant-Murley was improved significantly at the last follow-up (91.7 ± 8.3) in comparison to that preoperatively (40.6 ± 10.3) (P < 0.05). The mean range of motion in forward flexion was 38.25° ± 9.36° preoperatively and significantly improved to 162.48° ± 12.68° at 6-month follow-up (P < 0.05). CONCLUSION: The anatomical reconstruction procedure by open reduction and bone augmentation for the treatment of locked posterior shoulder dislocation with reverse Hill-Sachs lesion was promising in both fracture healing and functional outcomes.
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Lesões de Bankart/cirurgia , Transplante Ósseo/métodos , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Luxação do Ombro/cirurgia , Adulto , Aloenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Ossos Pélvicos/transplante , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
The use of Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) in adoptive immunotherapy in hematopoietic stem cell transplantation (HSCT) patients with post-transplantation lymphoproliferative disorder (PTLD) has demonstrated safety and effectiveness. EBV-CTLs might also be the effective treatment of refractory PTLD of solid organ transplantation (SOT) recipients. Two independent assessors searched Pubmed, Embase, Cochrane Library, and Web of Science from their inception to November 2020. Eleven studies with 76 patients (42, 55% male) were included. We extracted the data and completed the quality assessments. Most of the studies were from Europe and the USA. Liver and kidney transplantation accounted for most of the transplant types. Thirty-five (46.1%) patients were diagnosed with monomorphic PTLD, and B lymphocyte type was the most common. All the patients received primary treatment for PTLD while it was ineffective. CTLs included autologous EBV-CTLs (15/76, 22%) and HLA-matched third-party EBV-CTLs (61/76, 78%). The response rate for EBV-CTL treatment of refractory PTLD was 66%. Of 50 patients, 36 achieved complete remission and 14 achieved partial remission. EBV-DNA level decreased in 39 patients. Adverse reactions were rare and mild. We conclude that adoptive therapy with EBV-specific CTLs is safe, well-tolerated, and effective in PTLD.
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Infecções por Vírus Epstein-Barr , Transplante de Rim , Transtornos Linfoproliferativos , Feminino , Herpesvirus Humano 4 , Humanos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia , Masculino , Linfócitos T CitotóxicosRESUMO
Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening people's health and life. As the main effective component of Tripterygium wilfordii,triptolide( TP) has attracted increasing attention due to its multitarget and multi-pathway anti-tumor activity. Recent studies have revealed that breast cancer-sensitive TP enables the inactivation of breast cancer cells by inducing tumor cell apoptosis and autophagy,interfering in tumor cell metastasis,resisting drug resistance,arresting tumor cell cycle,and influencing tumor microenvironment. It has been recognized as a promising clinical antitumor agent by virtue of its widely accepted therapeutic efficacy. This paper reviewed the anti-breast cancer action and its molecular mechanisms of TP on the basis of the relevant literature in the past ten years,and proposed application strategies in view of the inadequacy of TP to provide a reference for further research on the application of TP in the treatment of breast cancer.
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Neoplasias da Mama , Diterpenos , Fenantrenos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Diterpenos/farmacologia , Compostos de Epóxi , Feminino , Humanos , Microambiente TumoralRESUMO
The evolutionary success of phytophagous insects depends on their ability to efficiently exploit plants as a source of energy for survival. Herbivorous insects largely depend on the efficiency, flexibility, and diversity of their digestive physiology and sophistication of their detoxification system to use chemically diverse host plants as food sources. The fall armyworm, Spodoptera frugiperda (J.E. Smith), is a polyphagous pest of many commercially important crops. To elucidate the ability of this insect pest to adapt to host plant mechanisms, we evaluated the impact of primary (corn) and alternate (rice) host plants after 11 generations on gut digestive enzymatic activity and expression profiles of related genes. Results indicated that the total protease and class-specific trypsin- and chymotrypsin-like protease activity of S. frugiperda significantly differed among host plant treatments. The class-specific protease profiles greatly differed in S. frugiperda midguts upon larval exposure to different treatments with inhibitors compared with treatments without inhibitors. Similarly, the single and cumulative effects of the enzyme-specific inhibitors TLCK, TPCK, and E-64 significantly increased larval mortality and reduced larval growth/mass across different plant treatments. Furthermore, the quantitative reverse transcription polymerase chain reaction results revealed increased transcription of two trypsin (SfTry-3, SfTry-7) and one chymotrypsin gene (Sfchym-9), which indicated that they have roles in host plant adaptation. Knockdown of these genes resulted in significantly reduced mRNA expression levels of the trypsin genes. This was related to the increased mortality observed in treatments compared with the dsRED control. This result indicates possible roles of S. frugiperda gut digestive enzymes and related genes in host plant adaptation.
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Adaptação Fisiológica/genética , Sistema Digestório/metabolismo , Endopeptidases , Herbivoria , Spodoptera , Animais , Quimotripsina/genética , Produtos Agrícolas , Digestão/efeitos dos fármacos , Sistema Digestório/efeitos dos fármacos , Endopeptidases/efeitos dos fármacos , Endopeptidases/genética , Endopeptidases/metabolismo , Genes de Insetos , Herbivoria/efeitos dos fármacos , Herbivoria/genética , Herbivoria/fisiologia , Larva/efeitos dos fármacos , Larva/genética , Larva/metabolismo , Oryza , Controle de Pragas , Inibidores de Proteases/farmacologia , Interferência de RNA , Spodoptera/efeitos dos fármacos , Spodoptera/genética , Spodoptera/metabolismo , Transcriptoma , Tripsina/genética , Zea maysRESUMO
Whether serine protease inhibitor Kazal type 1 (SPINK1) being associated with enzalutamide (Enz) resistance and metastasis of castration-resistant prostate cancer (CRPC) has not been clear. SPINK1 promoted Enz resistance by upregulating Androgen receptor splicing variant 7 (ARv7), and enhanced the invasion/migration of Enz-resistant cells via ERK/p38/ MMP9 signaling. Furthermore, miR-5089-5p suppressed SPINK1 mRNA through direct binding to its 3'UTR, and reversed its pro-proliferative and pro-metastatic effects. Mice bearing SPINK1-knockdown Enz-resistant PCa tumors showed significantly longer survival compared with those bearing wild-type tumors, while treatment with miR-5089-5p inhibitor abrogated the protective effects of SPINK1 knockdown. Taken together, SPINK1 can be used as a biomarker of resistance to Enz, and the miR-5089-5p/SPINK1/MAPK/MMP9 axis is a suitable therapeutic target against Enz-resistant and metastatic CRPC.Methods: The expression of SPINK1 in Enz-resistant prostate cancer (PCa) cell lines was detected through next-generation sequencing data and metastatic PCa patients. In vivo and in vitro experiments were performed to investigate the role of SPINK1 in Enz-resistance and metastasis.
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Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , MicroRNAs/farmacologia , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Processamento Alternativo , Animais , Benzamidas , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/genética , Metástase Neoplásica , Nitrilas , Feniltioidantoína/uso terapêutico , Receptores Androgênicos/genética , Análise de Sobrevida , Inibidor da Tripsina Pancreática de Kazal/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Image-guided surgery plays a crucial role in realizing complete tumor removal, reducing postoperative recurrence and increasing patient survival. However, imaging of tumor lesion in the typical metabolic organs, e.g., kidney and liver, still has great challenges due to the intrinsic nonspecific accumulation of imaging probes in those organs. Herein, we report an in situ self-assembled near-infrared (NIR) peptide probe with tumor-specific excretion-retarded (TER) effect in tumor lesions, enabling high-performance imaging of human renal cell carcinoma (RCC) and achieving complete tumor removal, ultimately reducing postoperative recurrence. The NIR peptide probe first specifically recognizes αvß3 integrin overexpressed in renal cancer cells, then is cleaved by MMP-2/9, which is up-regulated in the tumor microenvironment. The probe residue spontaneously self-assembles into nanofibers that exhibit an excretion-retarded effect in the kidney, which contributes to a high signal-to-noise (S/N) ratio in orthotopic RCC mice. Intriguingly, the TER effect also enables precisely identifying eye-invisible tiny lesions (<1 mm), which contributes to complete tumor removal and significantly reduces the postoperative recurrence compared with traditional surgery. Finally, the TER strategy is successfully employed in high-performance identification of human RCC in an ex vivo kidney perfusion model. Taken together, this NIR peptide probe based on the TER strategy is a promising method for detecting tumors in metabolic organs in diverse biomedical applications.
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Carcinoma de Células Renais/cirurgia , Corantes Fluorescentes/química , Neoplasias Renais/cirurgia , Peptídeos/química , Cirurgia Assistida por Computador , Animais , Carcinoma de Células Renais/diagnóstico por imagem , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Corantes Fluorescentes/síntese química , Humanos , Raios Infravermelhos , Neoplasias Renais/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Óptica , Tamanho da Partícula , Peptídeos/síntese química , Razão Sinal-Ruído , Propriedades de SuperfícieRESUMO
Nowadays,the advantages of traditional Chinese medicine(TCM) for treatment of tumors are increasingly prominent.Triptolide shows wide-spectrum and highly effective anti-tumor activity. Moreover,nano-carrier-based triptolide drug delivery system is more powerful in improving water solubility and pharmacokinetic behavior of the drug,but it is easy to cause toxic and side effects that should not be neglected on human body. Because of tumor vascular heterogeneity and PEGylation dilemma,nanoparticulate drug delivery systems need to overcome multiple physiological and pathological barriers from drug administration to functioning. It is difficult for traditional triptolide nanoparticulate drug delivery systems to achieve active accumulation of nano-drug in tumor tissues and specific drug release in tumor target site solely relying on enhanced permeability and retention effect of solid tumor,limiting their application and clinical transformation in treatment of tumors. Based on the traditional nano-preparation system,the new functionalized nano-drug delivery system further enhances the nano-drug enrichment,penetration and controlled release at the tumor sites,which is of great significance in improving bioavailability,anti-tumor efficacy and reducing the side effects of drugs. In this paper,we summarized and analyzed the researches on new triptolide functionalized nano-drug delivery system from four perspectives,including tumor active targeting,tumor microenvironment response,polymer-drug conjugates,and multidrug co-delivery for tumor treatment,expecting to provide ideas for in-depth research and clinical application of triptolide and some other active anti-tumor TCM ingredients.
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Diterpenos/química , Sistemas de Liberação de Medicamentos , Nanopartículas , Fenantrenos/química , Compostos de Epóxi/química , HumanosRESUMO
Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.
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Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Neoplasias/tratamento farmacológico , Fenantrenos/farmacologia , Tripterygium/química , Apoptose , Autofagia , Pontos de Checagem do Ciclo Celular , Compostos de Epóxi/farmacologia , HumanosRESUMO
BACKGROUND: The purpose of this study was to compare the surgical outcomes of a Colorado microdissection needle (CMN) with that of a standard-size electrocautery needle in one-stage hypospadias repair using a transverse preputial island flap (TPIF). METHODS: The records of patients who received hypospadias repair from September 2012 to October 2013 were retrospectively reviewed. Patients were divided into a group that received repair using a CMN and those in which a standard-size electrocautery needle was used. Data collected and compared included age, types of hypospadias, duration of surgery, intraoperative blood loss, and postoperative edema and complications. RESULTS: There were 51 patients in the CMN group and 44 in the standard needle group, and the groups were similar with respect to age and type of hypospadias. The median surgery time for the CMN group was significantly shorter than that of the standard group (15.7 minutes vs. 20.6 minutes, respectively, P<0.001). At postoperative day 7 and day 30, the CMN group had significantly less patients with edema than the standard needle group (31.4% vs. 65.9%, P<0.01; and 37.3% vs. 79.5%, P<0.001, respectively). The overall complication rate has no significant difference between two groups. CONCLUSIONS: The use of CMN for tissue dissection and separation in hypospadias repair can facilitate foreskin degloving, shape the flap in a more efficient way, and help maintain adequate blood supply for the new urethra and its skin coverage.