RESUMO
Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the western blot data shown for the MMP9 experiment in Fig. 4 on p. 1493 were strikingly similar to the western blots shown for the totalAkt experiments in Fig. 6 on p. 1494. After having reexamined their original data files, the authors realized that Fig. 6 had been inadvertently assembled incorrectly. The revised version of Fig. 6, containing the correct data for the totalAkt experiments, is shown below. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 31: 14891497, 2014; DOI: 10.3892/or.2013.2961].
RESUMO
Cryptococcus neoformans (C. neoformans) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera (B. rhynchopetera), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans, with a minimum inhibitory concentration (MIC) of 0.81 µM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans.
Assuntos
Antifúngicos , Peptídeos Antimicrobianos , Besouros , Cryptococcus neoformans , Testes de Sensibilidade Microbiana , Cryptococcus neoformans/efeitos dos fármacos , Animais , Antifúngicos/farmacologia , Antifúngicos/química , Besouros/microbiologia , Besouros/efeitos dos fármacos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Humanos , Biofilmes/efeitos dos fármacos , Sequência de AminoácidosRESUMO
Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.
Assuntos
Pontos de Acupuntura , Pressão Sanguínea , Hipertensão , Estimulação Elétrica Nervosa Transcutânea , Humanos , Hipertensão/terapia , Hipertensão/fisiopatologiaRESUMO
OBJECTIVE: The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab. METHODS: This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0 years, mean weight 58.7 ± 18.2 kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10 mg/kg, with an initial infusion every 2 weeks for the first 3 doses, followed by an infusion every 4 weeks. RESULTS: Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved (p < .05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased (p < .05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment (p > .05). CONCLUSION: Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation.
Assuntos
Anticorpos Monoclonais Humanizados , Lúpus Eritematoso Sistêmico , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Estudos Retrospectivos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Resultado do Tratamento , Trombocitopenia/tratamento farmacológico , Imunossupressores/efeitos adversos , Índice de Gravidade de DoençaRESUMO
SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.
Assuntos
Brônquios , COVID-19 , Degranulação Celular , Mastócitos , SARS-CoV-2 , Traqueia , Animais , Mastócitos/virologia , Mastócitos/imunologia , COVID-19/imunologia , COVID-19/virologia , COVID-19/patologia , Camundongos , Traqueia/virologia , Traqueia/patologia , Brônquios/virologia , Brônquios/patologia , Humanos , Inflamação/virologia , Células Epiteliais/virologia , Modelos Animais de DoençasRESUMO
Objective: Hashimoto's thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Methods: Forty patients with Hashimoto's thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results: After 6 months of a low-carbohydrate diet, patients with Hashimoto's thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63-614.62) vs 89.45 (15.9-215.67); TgAb: 17.05 (1.47-81.64) vs 4.1 (0.51-19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto's thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion: Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto's thyroiditis.
RESUMO
This study aimed to explore the magnetic resonance imaging (MRI) features of dual-phenotype hepatocellular carcinoma (DPHCC) and their diagnostic value.The data of 208 patients with primary liver cancer were retrospectively analysed between January 2016 and June 2021. Based on the pathological diagnostic criteria, 27 patients were classified into the DPHCC group, 113 patients into the noncholangiocyte-phenotype hepatocellular carcinoma (NCPHCC) group, and 68 patients with intrahepatic cholangiocarcinoma (ICC) were classified into the ICC group. Two abdominal radiologists reviewed the preoperative MRI features by a double-blind method. The MRI features and key laboratory and clinical indicators were compared between the groups. The potentially valuable MRI features and key laboratory and clinical characteristics for predicting DPHCC were identified by univariate and multivariate analyses, and the odds ratios (ORs) were recorded. In multivariate analysis, tumour without capsule (P = 0.046, OR = 9.777), dynamic persistent enhancement (P = 0.006, OR = 46.941), and targetoid appearance on diffusion-weighted imaging (DWI) (P = 0.021, OR = 30.566) were independently significant factors in the detection of DPHCC compared to NCPHCC. Serum alpha-fetoprotein (AFP) > 20 µg/L (P = 0.036, OR = 67.097) and prevalence of hepatitis B virus (HBV) infection (P = 0.020, OR = 153.633) were independent significant factors in predicting DPHCC compared to ICC. The differences in other tumour marker levels and imaging features between the groups were not significant. In MR enhanced and diffusion imaging, tumour without capsule, persistent enhancement and DWI targetoid findings, combined with AFP > 20 µg/L and HBV infection-positive laboratory results, can help to diagnose DPHCC and differentiate it from NCPHCC and ICC. These results suggest that clinical, laboratory and MRI features should be integrated to construct an AI diagnostic model for DPHCC.
Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Meios de Contraste , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Fenótipo , Estudos Retrospectivos , Método Duplo-CegoRESUMO
Primary vaginal cancer is rare, accounting for only 2% of all gynecological malignant tumors. Primary vaginal cell carcinoma is mainly squamous cell carcinoma, accounting for about 90%, and adenocarcinoma only accounts for 8-10%. Primary signet ring cell carcinoma of vagina is rare and has not been reported in the literature. This paper reports a case of signet ring cell carcinoma in vagina.
RESUMO
Objective: To establish a logistic regression model based on CT and MRI imaging features and Epstein-Barr (EB) virus nucleic acid to develop a diagnostic score model to differentiate extranodal NK/T nasal type (ENKTCL) from diffuse large B cell lymphoma (DLBCL). Methods: This study population was obtained from two independent hospitals. A total of 89 patients with ENKTCL (n = 36) or DLBCL (n = 53) from January 2013 to May 2021 were analyzed retrospectively as the training cohort, and 61 patients (ENKTCL=27; DLBCL=34) from Jun 2021 to Dec 2022 were enrolled as the validation cohort. All patients underwent CT/MR enhanced examination and EB virus nucleic acid test within 2 weeks before surgery. Clinical features, imaging features and EB virus nucleic acid results were analyzed. Univariate analyses and multivariate logistic regression analyses were performed to identify independent predictors of ENKTCL and establish a predictive model. Independent predictors were weighted with scores based on regression coefficients. A receiver operating characteristic (ROC) curve was created to determine the diagnostic ability of the predictive model and score model. Results: We searched for significant clinical characteristics, imaging characteristics and EB virus nucleic acid and constructed the scoring system via multivariate logistic regression and converted regression coefficients to weighted scores. The independent predictors for ENKTCL diagnosis in multivariate logistic regression analysis, including site of disease (nose), edge of lesion (blurred), T2WI (high signal), gyrus like changes, EB virus nucleic acid (positive), and the weighted score of regression coefficient was 2, 3, 4, 3, 4 points. The ROC curves, AUCs and calibration tests were carried out to evaluate the scoring models in both the training cohort and the validation cohort. The AUC of the scoring model in the training cohort were 0.925 (95% CI, 0.906-0.990) and the cutoff point was 5 points. In the validation cohort, the AUC was 0.959 (95% CI, 0.915-1.000) and the cutoff value was 6 points. Four score ranges were as follows: 0-6 points for very low probability of ENKTCL, 7-9 points for low probability; 10-11 points for middle probability; 12-16 points for very high probability. Conclusion: The diagnostic score model of ENKTCL based on Logistic regression model which combined with imaging features and EB virus nucleic acid. The scoring system was convenient, practical and could significantly improve the diagnostic accuracy of ENKTCL and the differential diagnosis of ENKTCL from DLBCL.
RESUMO
Objective: The purpose was to compare the accuracy of extraprostatic extension (EPE) grade on MRI predicting EPE with Partin tables, Memorial Sloan Kettering Cancer Center nomogram (MSKCCn), and combined models and to analyze the clinical incremental value of EPE grade. Materials and Methods: 105 prostate cancer patients confirmed by pathology after radical prostatectomy in our hospital from 2017 to 2021 were selected. The clinical stage, PSA, Gleason score, number of positive biopsy cores, and percentage of positive biopsy cores were recorded. Evaluate EPE grade according to EPE grade criteria, and calculate the probability of predicting EPE with Partin tables and MSKCCn. EPE grade is combined with Partin tables and MSKCCn to construct EPE grade+Partin tables and EPE grade+MSKCCn models. Calculate the area under the curve (AUC), sensitivity, and specificity of EPE grade, Partin tables, MSKCCn, EPE grade+Partin tables, and EPE grade+MSKCCn and compare their diagnostic efficacy. The clinical decision curve was used to analyze the clinical net income of each prediction scheme. Results: The AUC of EPE grade was 0.79, Partin tables was 0.50, MSKCCn was 0.78, the EPE grade+Partin table model was 0.79, and the EPE grade+MSKCCn model was 0.83. After EPE grade was combined with Partin tables and MSKCCn, the diagnostic efficiency of clinical model was significantly improved (P < 0.05). There was no significant difference in the diagnostic efficacy of the combined model compared with the single EPE grade (P > 0.05). The calibration curve of the combined model shows that it has a good calibration degree for EPE. In the analysis of the decision curve, the net income of the EPE grade is higher than that of Partin tables and MSKCCn and is equal to the EPE grade+Partin tables and is slightly lower than that of EPE grade+MSKCCn. The clinical net income of the combined model is obviously higher than that of individual clinical models. Conclusion: The accuracy of EPE classification in predicting prostate cancer EPE is high, and combined with the clinical model, it can significantly improve the diagnostic efficiency of the clinical model and increase the clinical benefit.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Próstata , Humanos , Masculino , Estadiamento de Neoplasias , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgiaRESUMO
We aimed to further explore the CT features of gastric schwannoma (GS), propose and validate a convenient diagnostic scoring system to distinguish GS from gastric gastrointestinal stromal tumors (GISTs) preoperatively. 170 patients with submucosal tumors pathologically confirmed (GS n=35; gastric GISTs n=135) from Hospital 1 were analyzed retrospectively as the training cohort, and 72 patients (GS=11; gastric GISTs=61) from Hospital 2 were enrolled as the validation cohort. We searched for significant CT imaging characteristics and constructed the scoring system via binary logistic regression and converted regression coefficients to weighted scores. The ROC curves, AUCs and calibration tests were carried out to evaluate the scoring models in both the training cohort and the validation cohort. For convenient assessment, the system was further divided into four score ranges and their diagnostic probability of GS was calculated respectively. Four CT imaging characteristics were ultimately enrolled in this scoring system, including transverse position (2 points), location (5 points), perilesional lymph nodes (6 points) and pattern of enhancement (2 points). The AUC of the scoring model in the training cohort were 0.873 (95% CI, 0.816-0.929) and the cutoff point was 6 points. In the validation cohort, the AUC was 0.898 (95% CI, 0.804-0.957) and the cutoff value was 5 points. Four score ranges were as follows: 0-3 points for very low probability of GS, 4-7 points for low probability; 8-9 points for middle probability; 10-15 points for very high probability. A convenient scoring model to preoperatively discriminate GS from gastric GISTs was finally proposed.
RESUMO
Objective: To investigate clinical characteristics, radiological features and biomarkers of pancreatic metastases of small cell lung carcinoma (PM-SCLC), and establish a convenient nomogram diagnostic predictive model to differentiate PM-SCLC from pancreatic ductal adenocarcinomas (PDAC) preoperatively. Methods: A total of 299 patients with meeting the criteria (PM-SCLC n=93; PDAC n=206) from January 2016 to March 2022 were retrospectively analyzed, including 249 patients from hospital 1 (training/internal validation cohort) and 50 patients from hospital 2 (external validation cohort). We searched for meaningful clinical characteristics, radiological features and biomarkers and determined the predictors through multivariable logistic regression analysis. Three models: clinical model, CT imaging model, and combined model, were developed for the diagnosis and prediction of PM-SCLC. Nomogram was constructed based on independent predictors. The receiver operating curve was undertaken to estimate the discrimination. Results: Six independent predictors for PM-SCLC diagnosis in multivariate logistic regression analysis, including clinical symptoms, CA199, tumor size, parenchymal atrophy, vascular involvement and enhancement type. The nomogram diagnostic predictive model based on these six independent predictors showed the best performance, achieved the AUCs of the training cohort (n = 174), internal validation cohort (n = 75) and external validation cohort (n = 50) were 0.950 (95%CI, 0.917-0.976), 0.928 (95%CI, 0.873-0.971) and 0.976 (95%CI, 0.944-1.00) respectively. The model achieved 94.50% sensitivity, 83.20% specificity, 86.80% accuracy in the training cohort and 100.00% sensitivity, 80.40% specificity, 86.70% accuracy in the internal validation cohort and 100.00% sensitivity, 88.90% specificity, 87.50% accuracy in the external validation cohort. Conclusion: We proposed a noninvasive and convenient nomogram diagnostic predictive model based on clinical characteristics, radiological features and biomarkers to preoperatively differentiate PM-SCLC from PDAC.
RESUMO
Atherosclerosis is a chronic inflammatory disease with high prevalence and mortality. The rupture of atherosclerotic plaque is the main reason for the clinical events caused by atherosclerosis. Making clear the transcriptomic and proteomic profiles between the stabe and unstable atherosclerotic plaques is crucial to prevent the clinical manifestations. In the present study, 5 stable and 5 unstable human carotid atherosclerotic plaques were obtained by carotid endarterectomy. The samples were used for the whole transcriptome sequencing (RNA-Seq) by the Next-Generation Sequencing using the Illumina HiSeq, and for proteome analysis by HPLC-MS/MS. The lncRNA-targeted genes and circRNA-originated genes were identified by analyzing their location and sequence. Gene Ontology and KEGG enrichment was carried out to analyze the functions of differentially expressed RNAs and proteins. The protein-protein interactions (PPI) network was constructed by the online tool STRING. The consistency of transcriptome and proteome were analyzed, and the lncRNA/circRNA-miRNA-mRNA interactions were predicted. As a result, 202 mRNAs, 488 lncRNAs, 91 circRNAs, and 293 proteins were identified to be differentially expressed between stable and unstable atherosclerotic plaques. The 488 lncRNAs might target 381 protein-coding genes by cis-acting mechanisms. Sequence analysis indicated the 91 differentially expressed circRNAs were originated from 97 protein-coding genes. These differentially expressed RNAs and proteins were mainly enriched in the terms of the cellular response to stress or stimulus, the regulation of gene transcription, the immune response, the nervous system functions, the hematologic activities, and the endocrine system. These results were consistent with the previous reported data in the dataset GSE41571. Further analysis identified CD5L, S100A12, CKB (target gene of lncRNA MSTRG.11455.17), CEMIP (target gene of lncRNA MSTRG.12845), and SH3GLB1 (originated gene of hsacirc_000411) to be critical genes in regulating the stability of atherosclerotic plaques. Our results provided a comprehensive transcriptomic and proteomic knowledge on the stability of atherosclerotic plaques.
RESUMO
BACKGROUND: Double-balloon enteroscopy (DBE) enables the detection of ulcerations in the small bowel. However, determining an etiological diagnosis remains challenging. This study was conducted to investigate the clinical and endoscopic features of ulcerations with isolated involvement of the small bowel (UIISB) to improve diagnostic ability. METHODS: Patients (n = 565) who underwent DBE and presented with ulcerations in the small bowel at Nanfang Hospital from January 2005 to January 2018 were eligible. Medical records were retrospectively examined. Predictors to determine ulceration etiology were identified by logistic regression analysis. RESULTS: After excluding patients with extra-ulcerations in other sites (n = 306) and those without follow-up records (n = 50), 209 patients with UIISB were enrolled. Among them, 59.3% of the ulcers were in the ileum, 26.8% in the jejunum, and 13.4% in the jejunoileum. Initial symptoms included abdominal pain (54.1%) and obscure gastrointestinal bleeding (30.0%). The multiplicity of ulceration was categorized as a single (22.0%) or multiple (78.0%). Cases were diagnosed with Crohn's disease (50.7%), chronic nonspecific inflammation (21.5%), diverticulum (9.1%), lymphoma (6.2%), gastrointestinal stromal tumor (4.3%), intestinal tuberculosis (1.9%), adenocarcinoma (1.4%), infective enteritis (1.4%), hemangioma (1.0%), cryptogenic multifocal ulcerous stenosing enteritis (1.0%), anastomotic ulcer (0.5%), intestinal duplication (0.5%), or neuroendocrine tumor (0.5%). Etiology identification indicated the if patients were aged 40 years or more, or had overt bleeding, single ulceration, and ulcer at jejunum, it as more prone to be neoplastic (P < .05). CONCLUSION: When we manage patients with UIISB, Crohn's disease should be first under consideration. Age≥40, overt bleeding, single ulceration, and ulcer at jejunum were reasonable indications for etiology of neoplasm or non-neoplasm.
Assuntos
Enteroscopia de Duplo Balão/métodos , Intestino Delgado/diagnóstico por imagem , Úlcera/diagnóstico por imagem , Dor Abdominal/etiologia , Adulto , Doença de Crohn/diagnóstico , Feminino , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Úlcera/etiologiaRESUMO
As one of the most widely used traditional Chinese medicine (TCM) treatment apparatus, the electric acu-point stimulation (such as electroacupuncture, transcutaneous acupoint electric stimulation, etc.) device plays an important role in improving the efficacy of acupuncture therapy and expanding its indications. The imbalance of human functional state has become an important factor affecting the health condition and quality of life. Acupuncture therapy has the advantage of regulating functional status of patients to restore the balance. Aiming at some problems of current acupuncture stimulation instruments in the stimulated depth, fuzzy range, lack of closed-loop feedback, insufficient combination with the theory of Chinese acupuncture-moxibustion, etc., we, in the present paper, put forward a new way of thinking that the classical theory of "Deqi" of acupuncture should be combined with the modern bio-electronic technology, multimode signal acquisition technology, real-time feedback control techno-logy, etc., in order to develop a series of effective, safe and comfortable integrated closed-loop feedback acupoint electrical stimulation devices. Interactions of multi-disciplines, reasonable coalesce between the medical treatment and theory, medical treatment and modern bioengineering techniques, as well as the integration of Chinese traditional and modern medicine will help promote the development of apparatuses of acupuncture-moxibustion for diagnosis and treatment of diseases. Such interdisciplinary efforts will make more contributions to the construction of healthy China and the health of all mankind.
Assuntos
Terapia por Acupuntura , Moxibustão , Pontos de Acupuntura , China , Estimulação Elétrica , Retroalimentação , Humanos , Qualidade de VidaRESUMO
Combining dual drugs in one vehicle to cancer cells offers spatiotemporal localization of drug at the site of action, leading to synergistic therapeutic effects and reduced side effects. To improve pH/redox responsiveness to the tumor microenvironments for cancer therapy, a pH/redox-responsive micelle based on poly(ε-caprolactone)-SS-poly(methacrylic acid) (PCL-SS-PMAA) diblock copolymer was fabricated for dual drug delivery. The PCL-SS-PMAA was formulated into a core-shell micelle (PSPm) in an aqueous solution. The critical micelle concentration (CMC) values of PSPm were 7.94 × 10-3 mg mL-1 at pH 5.0 and 1.00 × 10-2 mg mL-1 at pH 7.4. The hydrodynamic diameters of PSPm were within 210-270 nm, depending on pH values. Changes in morphology and size of PSPm were clearly observed before and after exposure to a reducing agent. Paclitaxel (PTX) was encapsulated into the core and cisplatin (CDDP) was chelated on the shell of PSPm, with both PTX and CDDP being efficiently released from PSPm in the presence of a reducing agent in an acid condition. MTT and annexin V/propidium iodide dual staining results demonstrated that co-loading of CDDP and PTX into PSPm had a synergistic effect in killing lung cancer cells and exerted superior antitumor activity over the combination of single drug-loaded PSPm or the combination of free-CDDP and free-PTX at equivalent drug amounts. Hence, encapsulating the dual drugs into PSPm exhibits a synergistic effect for potential lung cancer therapy.
Assuntos
Neoplasias Pulmonares , Micelas , Cisplatino/farmacologia , Portadores de Fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Oxirredução , Paclitaxel/farmacologia , Ácidos Polimetacrílicos , Microambiente TumoralRESUMO
OBJECTIVE: To explore the effective therapy for treating chronic scapulohumeral periarthritis of cold-damp stagnation. METHODS: A total of 90 cases of patients with chronic scapulohumeral periarthritis of cold-damp stagnation were randomly divided into an acupuncture and moxibustion group, a herbal cake separated moxibustion group and a routine rehabilitation group, 30 cases in each group. The routine rehabilitation group was treated with diclofenac sodium sustained-release tablets (0.1 g each time, taken after breakfast) and rehabilitation exercise, once a day. On the basis of the treatment in the routine rehabilitation group, the herbal cake separated moxibustion group was treated with herbal cake separated moxibustion at the affected side of Jianyu (LI 15), Jianliao (TE 14) and Jianzhen (SI 9), once a day. On the basis of the treatment in the herbal cake separated moxibustion group, the acupuncture and moxibustion group was additionally given umbrella shaped acupuncture with round sharp needle at the affected side of Jianyu (LI 15), Jianliao (TE 14), Jianzhen (SI 9), Naohui (TE 13), Jianqian (Extra), Jugu (LI 16), etc. once every other day. Each group was treated for 10 d. Before and after treatment the pain visual analogue scale (VAS) score and activities of daily living (ADL) score, and degree of changes in shoulder joint activity were compared in each group, and the clinical effect was evaluated. RESULTS: After treatment, the pain VAS scores of three groups were decreased (P<0.05), and the ADL scores were increased (P<0.05); the pain VAS score in the acupuncture and moxibustion group was lower than the herbal cake separated moxibustion group and the routine rehabilitation group after treatment (P<0.05), and the herbal cake separated moxibustion group was lower than the routine rehabilitation group (P<0.05); the ADL score in the acupuncture and moxibustion group after treatment was higher than the herbal cake separated moxibustion group and the routine rehabilitation group (P<0.05), and the herbal cake separated moxibustion group was higher than the routine rehabilitation group (P<0.05). The degree of changes in shoulder joint activity in the acupuncture and moxibustion group was larger than the herbal cake separated moxibustion group and the routine rehabilitation group, and the herbal cake separated moxibustion group was larger than the routine rehabilitation group (P<0.05). The total effective rate of the acupuncture and moxibustion group was 93.3% (28/30), which was higher than 83.3% (25/30) of the herbal cake separated moxibustion group and 73.3% (22/30) of the routine rehabilitation group (P<0.05). CONCLUSION: On the basis of routine rehabilitation training, herbal cake separated moxibustion combined with umbrella shaped acupuncture with round sharp needle treating chronic scapulohumeral periarthritis of cold-damp stagnation can significantly reduce shoulder joint pain and improve shoulder joint function.
Assuntos
Terapia por Acupuntura , Moxibustão , Periartrite , Atividades Cotidianas , Pontos de Acupuntura , Humanos , Periartrite/terapia , Resultado do TratamentoRESUMO
Angiogenesis in atherosclerotic plaque promotes plaque growth, causes plaque hemorrhage, and violates plaque stability. LINC00657 is a long noncoding RNA highly conserved and abundantly expressed in vascular endothelial cells. The present study was designed to investigate the effects and mechanisms of LINC00675 on low concentrations of oxidized low-density lipoprotein (oxLDL)-induced angiogenesis. Cell proliferation, transwell, wound healing, and tube formation assays were conducted to detect the effects of low concentrations of oxLDL on angiogenesis; the results discovered that oxLDL promoted cell proliferation, migration, and tube formation. oxLDL also upregulated LINC00657 expression. Inhibition of LINC00657 by siRNA significantly suppressed oxLDL-induced endothelial cell proliferation, migration, and tube formation. Bioinformatic assay indicated six binding sites in the LINC00657 sequence to miR-590-3p. The upregulation of LINC00657 was related to the downregulation of miR-590-3p in oxLDL-treated endothelial cells; while downregulation of LINC00657 resulted in upregulation of miR-590-3p. The antiangiogenesis effects of si-LINC00657 were partly abrogated by miR-590-3p inhibitor. Further dual-luciferase assay found miR-590-3p inhibited the expression of hypoxia-inducible factor 1α (HIF-1α) by binding to the position of 689-696 in HIF-1α 3'-untranslated region directly. MiR-590-3p also inhibited the oxLDL-induced upregulation of HIF-1α, vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). These results suggested that in oxLDL-treated endothelial cells, LINC00657 acted as a miR-590-3p sponge to attenuate the suppression of miR-590-3p on HIF-1α, and to promote angiogenesis through VEGF, MMP-2, and MMP-9. The present study provided new insight into the roles of LINC00657 and miR-590-3p in preventing oxLDL-induced angiogenesis and may provide a novel strategy for atherosclerosis treatment.
Assuntos
Indutores da Angiogênese/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lipoproteínas LDL/farmacologia , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MicroRNAs/genética , Oxirredução/efeitos dos fármacos , RNA Longo não Codificante/genéticaRESUMO
DJ-1 protein, as a multifunctional intracellular protein, has an important role in transcriptional regulation and anti-oxidant stress. A recent study by our group showed that DJ-1 can regulate the expression of certain antioxidant enzymes and attenuate hypoxia/reoxygenation (H/R)induced oxidative stress in the cardiomyocyte cell line H9c2; however, the detailed molecular mechanisms have remained to be elucidated. Nuclear factor erythroid 2like 2 (Nrf2) is an essential transcription factor that regulates the expression of several antioxidant genes via binding to the antioxidant response element (ARE). The present study investigated whether activation of the Nrf2 pathway is responsible for the induction of antioxidative enzymes by DJ1 and contributes to the protective functions of DJ1 against H/Rinduced oxidative stress in H9c2 cells. The results demonstrated that DJ1overexpressing H9c2 cells exhibited antioxidant enzymes, including manganese superoxide dismutase, catalase and glutathione peroxidase, to a greater extent and were more resistant to H/Rinduced oxidative stress compared with native cells, whereas DJ1 knockdown suppressed the induction of these enzymes and further augmented the oxidative stress injury. Determination of the importance of Nrf2 in DJ1mediated antioxidant enzymes induction and cytoprotection against oxidative stress induced by H/R showed that overexpression of DJ1 promoted the dissociation of Nrf2 from its cytoplasmic inhibitor Keap1, resulting in enhanced levels of nuclear translocation, AREbinding and transcriptional activity of Nrf2. Of note, Nrf2 knockdown abolished the DJ1mediated induction of antioxidant enzymes and cytoprotection against oxidative stress induced by H/R. In conclusion, these findings indicated that activation of the Nrf2 pathway is a critical mechanism by which DJ-1 upregulates anti-oxidative enzymes and attenuates H/R-induced oxidative stress in H9c2 cells.
Assuntos
Proteínas Associadas aos Microtúbulos/fisiologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Traumatismo por Reperfusão/metabolismo , Animais , Catalase/genética , Catalase/metabolismo , Hipóxia Celular , Linhagem Celular , Indução Enzimática , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteína Desglicase DJ-1 , Ratos , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
We have recently shown that DJ-1 is implicated in the delayed cardioprotective effect of hypoxic preconditioning (HPC) against hypoxia/reoxygenation (H/R) injury as an endogenous protective protein. This study aims to further investigate the underlying mechanism by which DJ-1 mediates the delayed cardioprotection of HPC against H/R-induced oxidative stress. Using a well-characterized cellular model of HPC from rat heart-derived H9c2 cells, we found that HPC promoted nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein-1 (Keap1) dissociation and resulted in increased nuclear translocation, antioxidant response element-binding, and transcriptional activity of Nrf2 24 hours after HPC, with subsequent upregulation of manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1), which provided delayed protection against H/R-induced oxidative stress in normal H9c2 cells. However, the aforementioned effects of HPC were abolished in DJ-1-knockdown H9c2 cells, which were restored by restoration of DJ-1 expression. Importantly, we showed that inhibition of the Nrf2 pathway in H9c2 cells mimicked the effects of DJ-1 knockdown and abolished HPC-derived induction of antioxidative enzymes (MnSOD and HO-1) and the delayed cardioprotection. In addition, inhibition of Nrf2 also reversed the effects of restored DJ-1 expression on induction of antioxidative enzymes and delayed cardioprotection by HPC in DJ-1-knockdown H9c2 cells. Taken together, this work revealed that activation of Nrf2 pathway and subsequent upregulation of antioxidative enzymes could be a critical mechanism by which DJ-1 mediates the delayed cardioprotection of HPC against H/R-induced oxidative stress in H9c2 cells.