RESUMO
OBJECTIVE: To evaluate the outcomes of minimally invasive cardiac surgery (MICS) compared with the sternotomy approach for Jehovah's Witness (JW) patients who cannot receive blood transfusions DESIGN: This was a retrospective observational study. SETTING: The study was conducted at a specialized cardiovascular intervention and surgery institute. PARTICIPANTS: The study cohort comprised JW patients undergoing cardiac surgery between September 2016 and July 2022. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Patients (n = 63) were divided into MICS (n = 19) and sternotomy (n = 44) groups, and clinical outcomes were analyzed. There was no difference in types of operation except coronary bypass grafting (n = 1 [5.3%] in the MICS group v n = 20 [45.5%] in the sternotomy group; p = 0.005). There were no between-group differences in early mortality and morbidities. Overall survival did not differ significantly during the follow-up period (mean, 43.9 ± 24.4 months). The amount of chest tube drainage was significantly lower in the MICS group on the first postoperative day (mean, 224.0 ± 122.7 mL v 334.0 ± 187.0 mL in the sternotomy group; p = 0.022). The mean hemoglobin level was significantly higher in the MICS group on the day of operation (11.7 ± 1.3 mg/dL v 10.6 ± 2.0 mg/dL in the sternotomy group; p = 0.042) and the first postoperative day (12.3 ± 1.8 mg/dL v 11.2 ± 1.9 mg/dL; p = 0.032). CONCLUSIONS: MICS for JW patients showed favorable early outcomes and mid-term survival compared to conventional sternotomy. MICS may be a viable option for JW patients who decline blood transfusions.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Testemunhas de Jeová , Procedimentos Cirúrgicos Minimamente Invasivos , Esternotomia , Humanos , Esternotomia/métodos , Masculino , Estudos Retrospectivos , Feminino , Procedimentos Cirúrgicos Cardíacos/métodos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Idoso , Transfusão de Sangue/estatística & dados numéricosRESUMO
Building on the preceding structural analysis and a structure-activity relationship (SAR) of 8-aryl-2-hexynyl nucleoside hA2AAR antagonist 2a, we strategically inverted C2/C8 substituents and eliminated the ribose moiety. These modifications aimed to mitigate potential steric interactions between ribose and adenosine receptors. The SAR findings indicated that such inversions significantly modulated hA3AR binding affinities depending on the type of ribose, whereas removal of ribose altered the functional efficacy via hA2AAR. Among the synthesized derivatives, 2-aryl-8-hexynyl adenine 4a demonstrated the highest selectivity for hA2AAR (Ki,hA2A = 5.0 ± 0.5 nM, Ki,hA3/Ki,hA2A = 86) and effectively blocked cAMP production and restored IL-2 secretion in PBMCs. Favorable pharmacokinetic properties and a notable enhancement of anticancer effects in combination with an mAb immune checkpoint blockade were observed upon oral administration of 4a. These findings establish 4a as a viable immune-oncology therapeutic candidate.
Assuntos
Adenina , Antagonistas do Receptor A2 de Adenosina , Nucleosídeos , Receptor A2A de Adenosina , Ribose , Humanos , Relação Estrutura-Atividade , Animais , Adenina/farmacologia , Adenina/química , Adenina/análogos & derivados , Antagonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/química , Antagonistas do Receptor A2 de Adenosina/síntese química , Nucleosídeos/química , Nucleosídeos/farmacologia , Nucleosídeos/síntese química , Ribose/química , Ribose/metabolismo , Receptor A2A de Adenosina/metabolismo , Camundongos , Estrutura Molecular , Ratos , Feminino , Linhagem Celular TumoralRESUMO
BACKGROUND: Music has been used to reduce stress and improve task performance during medical therapy. AIM: To assess the effects of music on colonoscopy performance outcomes. METHODS: We retrospectively reviewed patients who underwent colonoscopy performed by four endoscopists with popular music. Colonoscopy performance outcomes, such as insertion time, adenoma detection rate (ADR), and polyp detection rate (PDR), were compared between the music and non-music groups. To reduce selection bias, propensity score matching was used. RESULTS: After one-to-one propensity score matching, 169 colonoscopies were selected from each group. No significant differences in insertion time (4.97 vs 5.17 min, P = 0.795) and ADR (39.1% vs 46.2%, P = 0.226) were found between the two groups. Subgroup analysis showed that the insertion time (3.6 vs 3.8 min, P = 0.852) and ADR (51.1% vs 44.7%, P = 0.488) did not significantly differ between the two groups in experts. However, in trainees, PDR (46.9% vs 66.7%, P = 0.016) and ADR (25.9% vs 47.6%, P = 0.006) were significantly lower in the music than in the non-music group. CONCLUSION: The current study found that listening to music during colonoscopy did not affect procedure performance. Moreover, it suggested that music may distract trainees from appropriately detecting adenomas and polyps.
RESUMO
OBJECTIVE: This study aimed to evaluate the preference for antivascular endothelial growth factor (anti-VEGF) versus laser ablation therapy as primary and additional treatment in aggressive retinopathy of prematurity (ROP) and type 1 ROP. METHODS: This multicentre retrospective study was conducted at nine medical centres across South Korea. A total of 94 preterm infants with ROP who underwent primary treatment between January 2020 and December 2021 were enrolled. All eyes were classified as having type 1 ROP or aggressive ROP. Data on the zone, primary treatment chosen, injection dose, presence of reactivation and additional treatment were collected and analysed. RESULTS: Seventy infants (131 eyes) with type 1 ROP and 24 infants (45 eyes) with aggressive ROP were included. Anti-VEGF injection was selected as the primary treatment in 74.05% of the infants with type 1 ROP and 88.89% with aggressive ROP. Anti-VEGF injection was selected as the ROP was located in zone I or posterior zone II, and laser ablation was selected when it was located in zone II. The anti-VEGF injection doses varied and tended to be higher in the aggressive ROP group. Infants with aggressive ROP were 2.08 times more likely to require additional treatment than those with type 1 ROP. When ROP reactivation occurred, laser therapy was preferred as an additional treatment. CONCLUSION: In Korea, the preference for anti-VEGF therapy or laser therapy differed according to ROP subtype, zone and primary or secondary treatment. These findings suggest that ROP treatment are considered according to ROP subtype, location and reactivation.
Assuntos
Retinopatia da Prematuridade , Lactente , Recém-Nascido , Humanos , Retinopatia da Prematuridade/terapia , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Recém-Nascido Prematuro , Estudos Retrospectivos , Injeções Intravítreas , Fatores de Crescimento Endotelial/uso terapêuticoRESUMO
BACKGROUND: Cementing a new liner into a secure, well-positioned metallic shell can be a less-invasive strategy in revision total hip arthroplasty (THA). This study aimed to report the mean 14-year outcomes of cementing highly cross-linked polyethylene (XLPE) liners into well-fixed acetabular shells in revision THAs. METHODS: This study reviewed a single-surgeon series of cementing XLPE liners into well-fixed acetabular components. Of the 52 hips (51 patients) evaluated, 48 hips (47 patients) that satisfied a minimum follow-up of 10 years were included. The Harris Hip score was used for clinical evaluation. Final hip radiographs were used to determine the extent of acetabular osteolysis and stability of the components. The mean age at index operation was 53 years (range, 32 to 72). The mean follow-up duration was 14 years (range, 10 to 18). RESULTS: The mean Harris Hip score improved from 58 points (range, 23-81) preoperatively to 91 points (range, 45-100) at the final evaluation (P < .001). A total of 3 acetabular rerevisions were performed, all for aseptic loosening of the outer shell. One postoperative dislocation occurred, but it was successfully treated with a closed reduction. Final radiographs showed a significant reduction in acetabular osteolysis (P < .001). Implant survivorship free from any rerevision was 93.3% (95% confidence interval, 85.9-100%) at 14 years. CONCLUSION: Cementing an XLPE liner into a well-fixed acetabular shell in revision THA demonstrated excellent clinical and radiographic outcomes at a mean of 14 years postoperatively. This technique could be a safe and durable option in the absence of XLPE liners compatible with preimplanted shells.
Assuntos
Artroplastia de Quadril , Prótese de Quadril , Osteólise , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Artroplastia de Quadril/métodos , Polietileno , Osteólise/etiologia , Osteólise/cirurgia , Falha de Prótese , Acetábulo/cirurgia , Reoperação , Desenho de Prótese , SeguimentosRESUMO
BACKGROUND: Tapered modular stems are increasingly used in revision total hip arthroplasty (THA) with deficient femoral bone stock. This study aimed to report the long-term outcomes of revision THA using a tapered and fluted modular stem. METHODS: Between December 1998 and February 2006, 113 revision THAs (110 patients) were performed with a tapered and fluted modular stem at a single institution. Hip radiographs were used to identify stem subsidence, stability, and femoral radiolucency. Final outcomes were assessed in 72 hips (70 patients), with a minimum follow-up of 10 years. RESULTS: The mean follow-up duration was 16 years (range, 10-23). At the final evaluation, the Harris Hip Score improved from a mean of 41 points (range, 10-72) preoperatively to 83 points (range, 56-100) (P < .001). Six femoral re-revisions were performed for the following reasons: 1 aseptic loosening, 2 stem fractures, and 3 infections. One stem fracture occurred at the modular junction after 14 years, and the other at a more distal location after 15 years. Stem subsidence was >5 mm in 6 hips (9.1%), but secondary stability was achieved in all stems. Osseointegration was observed in 63 (95.5%) hips. Stem survivorship was 91.1% with an end point of any re-revision and 94.6% for aseptic re-revision. CONCLUSION: A tapered and fluted modular stem demonstrated excellent implant survivorship with reliable bony fixation at a mean follow-up of 16 years. This type of stem can be a durable option for revision THA in patients who have femoral defects.
Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Desenho de Prótese , Seguimentos , Reoperação , Fêmur/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Falha de PróteseRESUMO
Acinar cell cystadenoma, also known as an acinar cystic transformation of the pancreas, is an exceedingly rare but benign pancreatic lesion. A 51-year-old woman was transferred to Inje University Busan Paik Hospital because of an 8 cm-sized calcified, multiseptated, and multilocular cystic mass in the pancreatic tail observed during abdominal CT performed at another hospital. The patient did not complain of abdominal pain or other symptoms, and her laboratory findings were normal. MRI showed that the cyst was not connected to the main pancreatic duct. A pancreatic serous cystadenoma was suspected, and a laparoscopic distal pancreatectomy was performed. The resected mass was composed of variable sized multilocular cysts with incomplete septa and focally lined by epithelium with acinar differentiation. The patient was diagnosed with acinar cell cystadenoma and is currently being followed up regularly. No complications or recurrences have been observed.
Assuntos
Cistadenoma Seroso , Cistadenoma , Neoplasias Pancreáticas , Células Acinares , Cistadenoma/diagnóstico , Cistadenoma/cirurgia , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgiaRESUMO
Prostate cancer (PCa) is a common disease among men especially in the old age. The deregulated activation of oncogenic and pro-survival transcription factors has been linked with tumor progression in PCa patients. The consequence of diosgenin treatment on NF-κB/STAT3 activation in PCa cells as well as transgenic mouse model was determined. We also validated the hypothesis of targeting these transcription factors using in silico proteomics simulation model. Diosgenin abrogated NF-κB/STAT3 activation and this action was caused as a result of suppression of protein kinases and reporter gene activity that led to a substantial reduction in the expression of various tumorigenic gene products. In vivo, diosgenin (2% w/w) when mixed in diet and fed to mice abrogated tumor progression in transgenic mice. Diosgenin was also detected in serum and was well absorbed orally. Overall, our data highlights the promising efficacy of diosgenin in PCa therapy.
Assuntos
Diosgenina/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Administração Oral , Animais , Linhagem Celular Tumoral , Simulação por Computador , Diosgenina/uso terapêutico , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Camundongos , Camundongos Transgênicos , NF-kappa B/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteômica , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (10,000, 20,000, and > 25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. 10,000 IEQ/kg (N = 2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and 20,000 IEQ/kg group (N = 5) achieved unstable control, with a high insulin requirement. However, 25,000 IEQ/kg (N = 4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated CD3+ T cell infiltration. In conclusion, the optimal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was > 25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.
Assuntos
Diabetes Mellitus Experimental/imunologia , Insulina/imunologia , Ilhotas Pancreáticas/imunologia , Macaca fascicularis/imunologia , Animais , Complexo CD3/imunologia , Teste de Tolerância a Glucose/métodos , Imuno-Histoquímica/métodos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/imunologia , Transplante das Ilhotas Pancreáticas/métodos , Transplante Heterólogo/métodosRESUMO
BACKGROUND: Posteroanterior and lateral cephalogram have been widely used for evaluating the necessity of orthognathic surgery. The purpose of this study was to develop a deep learning network to automatically predict the need for orthodontic surgery using cephalogram. METHODS: The cephalograms of 840 patients (Class ll: 244, Class lll: 447, Facial asymmetry: 149) complaining about dentofacial dysmorphosis and/or a malocclusion were included. Patients who did not require orthognathic surgery were classified as Group I (622 patients-Class ll: 221, Class lll: 312, Facial asymmetry: 89). Group II (218 patients-Class ll: 23, Class lll: 135, Facial asymmetry: 60) was set for cases requiring surgery. A dataset was extracted using random sampling and was composed of training, validation, and test sets. The ratio of the sets was 4:1:5. PyTorch was used as the framework for the experiment. RESULTS: Subsequently, 394 out of a total of 413 test data were properly classified. The accuracy, sensitivity, and specificity were 0.954, 0.844, and 0.993, respectively. CONCLUSION: It was found that a convolutional neural network can determine the need for orthognathic surgery with relative accuracy when using cephalogram.
Assuntos
Aprendizado Profundo , Má Oclusão Classe III de Angle , Má Oclusão , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Cefalometria , Humanos , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , República da CoreiaRESUMO
BACKGROUND: Although in most patients with inflammatory bowel diseases, conservative therapy is successful, a significant proportion of patients still require surgery once in their lifetime. Development of a safe perioperative treatment to dampen colitis activity without disturbance of anastomotic healing is an urgent and unmet medical need. Annexin A1 (ANXA1) has been shown to be effective in reducing colitis activity. Herein, a nanoparticle-based perioperative treatment approach was used for analysis of the effects of ANXA1 on the resolution of inflammation after surgery for colitis. METHODS: Anxa1-knockout mice were used to delineate the effects of ANXA1 on anastomotic healing. A murine model of preoperative dextran sodium sulfate colitis was performed. Collagen-IV-targeted polymeric nanoparticles, loaded with the ANXA1 biomimetic peptide Ac2-26 (Ac2-26-NPs), were synthesized and administered perioperatively during colitis induction. The effects of the Ac2-26-NPs on postoperative recovery and anastomotic healing were evaluated using the disease activity index, histological healing scores, and weight monitoring. Ultimately, whole-genome RNA sequencing of the anastomotic tissue was performed to unravel underlying molecular mechanisms. RESULTS: Anxa1-knockout exacerbated the inflammatory response in the healing anastomosis. Treatment with Ac2-26-NPs improved preoperative colitis activity (Pâ <â 0.045), postoperative healing scores (Pâ <â 0.018), and weight recovery (Pâ <â 0.015). Whole-genome RNA sequencing revealed that the suppression of proinflammatory cytokine and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling was associated with the treatment effects and a phenotypic switch toward anti-inflammatory M2 macrophages. CONCLUSIONS: Proresolving therapy with Ac2-26-NPs promises to be a potent perioperative therapy because it improves colitis activity and even intestinal anastomotic healing by the suppression of proinflammatory signaling.
Assuntos
Anexina A1 , Colite , NF-kappa B , Nanopartículas , Anastomose Cirúrgica , Animais , Anexina A1/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de SinaisRESUMO
Fibroma of tendon sheath (FTS) is an uncommon mass that arises from the tendon sheath of extremities. The tumor typically affects adults between ages 20 and 50 years with a predominance in males. To date, growth hormone (GH) treatment is safe for children with Turner syndrome without risk factors and is accepted worldwide. This article reports the case of a nine-year-old female patient with Turner syndrome and FTS during GH treatment. She had been treated with daily subcutaneous GH to improve growth failure with a mean dose of 0.28 mg/kg/week and the level of insulin-like growth factor-1 was within the normal range. During the follow-up period, she complained about a mass in her hand, subsequently diagnosed as FTS. This report illustrates the clinical impact of Turner syndrome and GH treatments on the occurrence of this tumor through literature reviews. Further studies are needed to highlight the association between FTS and GH treatment, especially in Turner syndrome.
Assuntos
Fibroma/induzido quimicamente , Hormônio do Crescimento/efeitos adversos , Mãos/patologia , Tendões/patologia , Síndrome de Turner/tratamento farmacológico , Criança , Feminino , Hormônio do Crescimento/administração & dosagem , HumanosRESUMO
OBJECTIVES: The cause of cervical lymphadenopathy varies from inflammation to malignancy. Accurate and prompt diagnosis is crucial as delayed detection of malignant lymph node can lead to a worse prognosis. To improve the diagnostic accuracy of metastatic lymph node, electrical spectroscopy was employed to study human normal and metastatic lymph nodes using a hypodermic needle with fine interdigitated electrodes on its tip (EoN). SUBJECTS AND METHODS: The electrical impedance of samples collected from 8 patients were analyzed in the sweeping frequency range from 1 Hz to 1 MHz. To align the impedance level data of the patients, normalized impedance was employed. RESULTS: The optimal frequency exhibiting the best discrimination results between the normal and cancerous tissues was introduced based on a discrimination index. A high sensitivity (86.2%) and specificity (88.9%) were obtained, which implied that the EoN holds the potential to improve the in vivo diagnostic accuracy of metastatic lymph node during biopsy and surgery. CONCLUSION: EoN has a promising potential to be utilized in real-time in actual clinical trials without a need for any pre/post-treatment during FNA or surgery. We believe that the EoN could reduce unnecessary operations with its associated morbidity.
Assuntos
Biópsia por Agulha/instrumentação , Espectroscopia Dielétrica , Eletrodos , Linfonodos/patologia , Metástase Linfática/diagnóstico , Biópsia por Agulha/métodos , Humanos , Metástase Linfática/patologia , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Epithelial-mesenchymal transition (EMT) is a process of transdifferentiation where epithelial cells attain mesenchymal phenotype to gain invasive properties and thus, can contribute to metastasis of tumor cells. OBJECTIVES: The antimetastatic and antitumor efficacy of brusatol (BT) was investigated in a hepatocellular carcinoma (HCC) model. METHODS: We evaluated the action of BT on EMT process using various biological assays in HCC cell lines and its effect on tumorigenesis in an orthotopic mouse model. RESULTS: We found that BT treatment restored the expression of Occludin, E-cadherin (epithelial markers) while suppressing the levels of different mesenchymal markers in HCC cells and tumor tissues. Moreover, we observed a decline in the expression of transcription factors (Snail, Twist). Since the expression of these two factors can be regulated by STAT3 signaling, we deciphered the influence of BT on modulation of this pathway. BT suppressed the phosphorylation of STAT3Y705 and STAT3 depletion using siRNA resulted in the restoration of epithelial markers. Importantly, BT (1mg/kg) reduced the tumor burden in orthotopic mouse model with a concurrent decline in lung metastasis. CONCLUSIONS: Overall, our results demonstrate that BT interferes with STAT3 induced metastasis by altering the expression of EMT-related proteins in HCC model.
RESUMO
PURPOSE: To investigate the tomographic structural changes in the retinal layers after internal limiting membrane (ILM) peeling for idiopathic epiretinal membrane (ERM). METHODS: Sixty-nine eyes treated with vitrectomy and ILM peeling for idiopathic ERM were analyzed. Parafoveal retinal thickness was measured at baseline and 6 months after surgery. RESULTS: Total retinal thickness decreased significantly in the nasal and temporal subfields after surgery (p < 0.001), whereas the inner nuclear layer and outer nuclear layer showed nasal thickening (all, p < 0.001). The postoperative temporal/nasal subfield thickness ratio of each layer was significantly lower than that of fellow eyes. Eyes with larger ILM peeling showed a significantly lower temporal/nasal subfield thickness ratio (p = 0.033) than those with smaller sizes. CONCLUSIONS: The retinal thickness of each layer showed anatomical changes from ILM peeling and ERM removal. Nasal parafoveal thickening and temporal thinning occurred in the inner retinal architecture, which might be affected by ILM peeling size.
Assuntos
Membrana Epirretiniana/cirurgia , Retina/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Vitrectomia/métodos , Idoso , Membrana Basal/patologia , Membrana Epirretiniana/diagnóstico , Feminino , Humanos , Masculino , Período Pós-Operatório , Estudos RetrospectivosRESUMO
Hepatocellular carcinoma (HCC) is a major malignancy that stands second in terms of global cancer-related mortality. STAT3 has been described as a latent transcription factor that promotes tumorigenesis. This study was designed to examine the effect of vitexin on STAT3 signaling and important hallmarks of cancer. HCC cells were employed to decipher the impact of vitexin on activation of STAT3 signaling using Western blotting, EMSA, immunocytochemistry, and reporter assay. The combinational apoptotic effects of vitexin with approved anti-cancer drugs was examined by live-dead assay, and its anti-invasive potential was studied using matrigel assay. The results obtained in cell-based assays were verified using in silico analysis. Vitexin effectively inhibited sustained activation of JAK1, JAK2, Src, and STAT3 in HCC cells. Vitexin downregulated DNA binding ability, reduced the nuclear pool of STAT3, and diminished epidermal growth factor (EGF)-driven STAT3 gene expression. Interestingly, treatment with tyrosine phosphatase inhibitor altered the vitexin-induced STAT3 phosphorylation, and the attenuation of STAT3 by vitexin was found to be driven through the upregulation of PTPεC. The combinational studies indicated that vitexin can exhibit substantial apoptotic effects with doxorubicin and sorafenib. It also suppressed the CXCL12-induced cell invasion. The results of cell-based assays are supported by in silico analysis as the vitexin displayed favorable interaction with kinase domain of JAK2 protein. Overall, this study demonstrated that vitexin can act as a potential blocker of the STAT3 signaling cascade and mitigate the survival as well as invasion of HCC cells.
Assuntos
Apigenina/farmacologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Invasividade NeoplásicaRESUMO
Cancer persists as one of the leading causes of deaths worldwide, contributing to approximately 9.6 million deaths per annum in recent years. Despite the numerous advancements in cancer treatment, there is still abundant scope to mitigate recurrence, adverse side effects and toxicities caused by existing pharmaceutical drugs. To achieve this, many phytochemicals from plants and natural products have been tested against cancer cell lines in vivo and in vitro. Likewise, casticin, a flavonoid extracted from the Vitex species, has been isolated from the leaves and seeds of V. trifolia and V. agnus-castus. Casticin possesses a wide range of therapeutic properties, including analgesic, anti-inflammatory, antiangiogenic, antiasthmatic and antineoplastic activities. Several studies have been conducted on the anticancer effects of casticin against cancers, including breast, bladder, oral, lung, leukemia and hepatocellular carcinomas. The compound inhibits invasion, migration and proliferation and induces apoptosis (casticin-induced, ROS-mediated and mitochondrial-dependent) and cell cycle arrest (G0/G1, G2/M, etc.) through different signaling pathways, namely the PI3K/Akt, NF-κB, STAT3 and FOXO3a/FoxM1 pathways. This review summarizes the chemo-preventive ability of casticin as an antineoplastic agent against several malignancies.
Assuntos
Proliferação de Células/efeitos dos fármacos , Flavonoides/uso terapêutico , Neoplasias/tratamento farmacológico , Apoptose/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Fatores de Transcrição Forkhead/genética , Humanos , Mitocôndrias/efeitos dos fármacos , Neoplasias/classificação , Neoplasias/patologia , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
Vascular endothelial cells are essential to vascular function and maintenance. Dysfunction of these cells can lead to the development of cardiovascular disease or contribute to tumorigenesis. As such, the therapeutic modulation and monitoring of vascular endothelial cells are of significant clinical interest, and several endothelial-specific ligands have been developed for drug delivery and the monitoring of endothelial function. However, the application of these ligands has been limited by their high cost and tendency to induce immune responses, highlighting a need for alternate methods of targeting vascular endothelial cells. In the present study, we explore the therapeutic potential of DNA aptamers. Using cell-SELEX technology, we identified two aptamers with specific binding affinity for vascular endothelial cells and propose that these molecules show potential for use as new ligands for drug and biomarker research concerning vascular endothelial cells.
Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Células Endoteliais/metabolismo , Ácidos Nucleicos Imobilizados/metabolismo , Animais , Biomarcadores/metabolismo , Carcinogênese/metabolismo , Doenças Cardiovasculares/metabolismo , Feminino , Ligantes , RatosRESUMO
The most obvious method to observe transplanted islets in the liver is direct biopsy, but the distribution and location of the best biopsy site in the recipient's liver are poorly understood. Islets transplanted into the whole liver of five diabetic cynomolgus monkeys that underwent insulin-independent survival for an extended period of time after allo-islet transplantation were analyzed for characteristics and distribution tendency. The liver was divided into segments (S1-S8), and immunohistochemistry analysis was performed to estimate the diameter, beta cell area, and islet location. Islets were more distributed in S2 depending on tissue size; however, the number of islets per tissue size was high in S1 and S8. Statistical analysis revealed that the characteristics of islets in S1 and S8 were relatively similar to other segments despite various transplanted islet dosages and survival times. In conclusion, S1, which exhibited high islet density and reflected the overall characteristics of transplanted islets, can be considered to be a reasonable candidate for a liver biopsy site in this monkey model. The findings obtained from the five monkey livers with similar anatomical features to human liver can be used as a reference for monitoring transplanted islets after clinical islet transplantation.
Assuntos
Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas , Fígado/citologia , Aloenxertos , Animais , Biópsia , Diabetes Mellitus Experimental/patologia , Feminino , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Insulina/metabolismo , Macaca fascicularis , MasculinoRESUMO
STAT3 is an oncogenic transcription factor that regulates the expression of genes which are involved in malignant transformation. Aberrant activation of STAT3 has been observed in a wide range of human malignancies and its role in negative prognosis is well-documented. In this report, we performed high-throughput virtual screening in search of STAT3 signaling inhibitors using a cheminformatics platform and identified 2-Amino-6-[2-(Cyclopropylmethoxy)-6-Hydroxyphenyl]-4-Piperidin-4-yl Nicotinonitrile (ACHP) as the inhibitor of the STAT3 signaling pathway. The predicted hit was evaluated in non-small cell lung cancer (NSCLC) cell lines for its STAT3 inhibitory activity. In vitro experiments suggested that ACHP decreased the cell viability and inhibited the phosphorylation of STAT3 on Tyr705 of NSCLC cells. In addition, ACHP imparted inhibitory activity on the constitutive activation of upstream protein tyrosine kinases, including JAK1, JAK2, and Src. ACHP decreased the nuclear translocation of STAT3 and downregulated its DNA binding ability. Apoptosis was evidenced by cleavage of caspase-3 and PARP with the subsequent decline in antiapoptotic proteins, including Bcl-2, Bcl-xl, and survivin. Overall, we report that ACHP can act as a potent STAT3 signaling inhibitor in NSCLC cell lines.