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1.
World J Clin Oncol ; 15(10): 1269-1279, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39473868

RESUMO

BACKGROUND: Cancer presents a significant public health challenge in China, necessitating broad collaboration across society. The Chinese government has articulated a goal to increase the overall five-year survival rate for cancer by 15% by 2030. Achieving this objective requires not only advances in medical technology, but also an improvement in the dissemination of knowledge pertaining to cancer prevention and treatment. AIM: To provide a comprehensive understanding of the status of cancer prevention and level of popularization in China in 2023. METHODS: From January 2023 to May 2023, online questionnaires were distributed to 3000 participants, including medical personnel, patients with cancer, their families, and the general public. There were 2711 valid responses, covering the entire nation. RESULTS: A total of 1020 medical personnel and 1691 patients with cancer, their family members, and the general public participated in the survey. Among medical personnel, 93.2% had popularized cancer health. Commonly addressed topics included cancer prevention (85.9%) and cancer screening (77.8%). Primary challenges included time constraints (73.9%), insufficient personnel and material support (66.7%), and uncertainty as to where to begin (49.3%). Among patients with cancer, their family members, and the general public, 93.4% reported reading or watching cancer science popularization materials and 56.9% expressed a desire for deeper understanding. The most sought-after topics in cancer science popularization included cancer screening (80.2%) and cancer prevention (75.8%). The greatest challenge encountered in accessing cancer health popularization was an abundance of misinformation (67.5%). CONCLUSION: Most clinical doctors, patients, family, and the general public wish to participate in cancer education. However, improvement in the quality of content in cancer prevention and treatment education is required.

2.
Comput Methods Programs Biomed ; 255: 108333, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39047576

RESUMO

BACKGROUND AND OBJECTIVE: Diabetic foot (DF) complications often lead to severe vascular issues. This study investigated the effectiveness of enhanced external counterpulsation (EECP) and its derived innovative compression strategies in addressing poor perfusion in DF. Although developing non-invasive and efficient treatment methods for DF is critical, the hemodynamic alterations during EECP remain underexplored despite promising outcomes in microcirculation. This research sought to address this gap by developing a patient-specific 0D-1D model based on clinical ultrasound data to identify potentially superior compression strategies that could substantially enhance blood flow in patients with DF complications. METHODS: Data were gathered from 10 patients with DF utilizing ultrasound for blood flow rate and computed tomography angiography (CTA) to identify lower limb conditions. Clinical measurements during standard EECP, with varying cuff pressures, facilitated the creation of a patient-specific 0D-1D model through a two-step parameter estimation process. The accuracy of this model was verified via comparison with the clinical measurements. Four compression strategies were proposed and rigorously evaluated using this model: EECP-Simp-I (removing hip cuffs), EECP-Simp-II (further removing the cuffs around the lower leg), EECP-Impr-I (removing all cuffs around the affected side), and EECP-Impr-II (building a loop circulation from the healthy side to the affected side). RESULTS: The predicted results under the rest and standard EECP states were generally closely aligned with clinical measurements. The patient-specific 0D-1D model demonstrated that EECP-Simp-I and EECP-Impr-I contributed similar enhancement to perfusion in the dorsal artery (DA) and were comparable to standard EECP, while EECP-Simp-II had the least effect and EECP-Impr-II displayed the most significant enhancement. Pressure at the aortic root (AO) remained consistent across strategies. CONCLUSIONS: EECP-Simp-I is recommended for patients with DF, emphasizing device simplification. However, EECP-Simp-II is discouraged as it significantly diminished blood perfusion in this study, except in cases of limb fragility. EECP-Impr-II showed superior enhancement of blood perfusion in DA to all other strategies but required a more complex EECP device. Despite increased AO pressure in all the proposed compression strategies, safety could be guaranteed as the pressue remained within a safe range.


Assuntos
Contrapulsação , Pé Diabético , Modelos Cardiovasculares , Humanos , Pé Diabético/terapia , Contrapulsação/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hemodinâmica , Angiografia por Tomografia Computadorizada
3.
Int Immunopharmacol ; 114: 109520, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36513022

RESUMO

BACKGROUND: Premature ovarian insufficiency is common in clinically infertile patients. The NOD-like receptor family pyrin domain-containing 3 (NLRP3)/Gasdermin D (GSDMD) signaling pathway plays a key role in premature ovarian insufficiency. Leonurine (Leo) is one of the important active ingredients extracted from Leonurus japonicus Houttuyn, which can inhibit NLRP3 activation. However, whether leonurine hydrochloride plays a protective role in premature ovarian insufficiency through actions on NLRP3/GSDMD signaling is not yet known. METHODS: After cyclophosphamide-induced premature ovarian insufficiency was established in female mice, Leo was injected intraperitoneally over four weeks to evaluate the ovarian function and anti-pyroptosis effects using the metrics of fertility, serum hormone level, ovary weight, follicle number, expression of NLRP3/GSDMD pathway-related proteins, and serum IL-18 and IL-1ß levels. RESULTS: Intraperitoneal administration of leonurine hydrochloride was found to significantly protect fertility and maintain both serum hormone levels and follicle number in mice with premature ovarian insufficiency. Mice treated with leonurine hydrochloride consistently resisted cyclophosphamide-induced ovarian damage by inhibiting the activation of NLRP3 inflammasome, Caspase-1 and GSDMD in both ovarian tissue and granulosa cells, which led to lower levels of IL-18 and IL-1ß in the serum (p < 0.05, p < 0.01, p < 0.001). CONCLUSION: Intraperitoneal administration of leonurine hydrochloride prevents cyclophosphamide-induced premature ovarian insufficiency in mice by inhibiting NLRP3/GSDMD-mediated pyroptosis.


Assuntos
Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos , Feminino , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Ciclofosfamida , Hormônios
4.
World J Gastroenterol ; 28(38): 5626-5635, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36304088

RESUMO

BACKGROUND: At present, there is insufficient medical evidence to determine whether adjuvant chemotherapy is necessary for T2N0M0 gastric cancer. AIM: To obtain a risk score to assess the need for adjuvant chemotherapy in patients with T2N0M0 gastric cancer. METHODS: We identified 325 patients with pathological T2N0M0 stage primary gastric cancer at the National Cancer Center between 2011 and 2018. Univariate and multivariate Cox regression analyses were performed to predict factors affecting prognosis. Vascular invasion, tumor site, and body mass index were assessed, and a scoring system was established. We compared the survival outcomes and benefits of adjuvant chemotherapy between the different subgroups. RESULTS: Five-year survival rates of the score 0, 1, 2, and 3 groups were 92%, 95%, 80%, and 50%, respectively (P < 0.001). In the score 2-3 group, five-year survival rates for patients in the adjuvant chemotherapy group and postoperative observation group were 95% and 61%, respectively (P = 0.021). CONCLUSION: For patients with T2N0M0 stage gastric cancer and two or more risk factors, adjuvant chemotherapy after D2 gastrectomy may have a survival benefit.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estadiamento de Neoplasias , Gastrectomia/efeitos adversos , Quimioterapia Adjuvante , Prognóstico , Estudos Retrospectivos
5.
Virology ; 577: 43-50, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36279602

RESUMO

Acquired immunodeficiency syndrome (AIDS) caused by Human immunodeficiency virus type 1 (HIV-1) has a high tendency among illicit drug abusers. Recently, it is reported that abuse of fentanyl, a potent synthetic µ receptor-stimulating opioid, is an independent risk factor for HIV-1 infection. However, the mechanism of action in augmenting HIV-1 infection still remains elusive. In this study, we found that fentanyl enhanced infection of HIV-1 in MT2 cells, primary macrophages and Jurkat C11 cells. Fentanyl up-regulated CXCR4 and CCR5 receptor expression, which facilitated the entry of virion into host cells. In addition, it down-regulated interferon-ß (IFN-ß) and interferon-stimulated genes (APOBEC3F, APOBEC3G and MxB) expression in MT2 cells. Our findings identify an essential role of fentanyl in the positive regulation of HIV-1 infection via the upregulation of co-receptors (CXCR4/CCR5) and downregulation of IFN-ß and ISGs, and it may have an important role in HIV-1 immunopathogenesis.

6.
World J Gastrointest Oncol ; 14(8): 1540-1551, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36160743

RESUMO

BACKGROUND: For Siewert type II/III adenocarcinoma of gastroesophageal junction (AGE), the efficacy of adjuvant chemoradiotherapy (CRT) after D2/R0 resection remains uncertain. AIM: To determine whether CRT was superior to chemotherapy (CT) alone after D2/R0 resection for locally advanced Siewert type II/III AGE. METHODS: We identified 316 locally advanced Siewert type II/III AGE patients who were treated with D2/R0 resection at National Cancer Center from 2011 to 2018. 57 patients received adjuvant CRT and 259 patients received adjuvant CT. We followed patients for overall survival (OS), relapse-free survival, and recurrence pattern. RESULTS: Five-year OS rates of the CRT group and the CT group for all patients were 66.7% and 41.9% (P = 0.010). Five-year OS rates of the CRT group and the CT group for Siewert type III AGE patients were 65.7% and 43.9% (P = 0.006). Among the 195 patients whose recurrence information could be obtained, 18 cases (34.6%) and 61 cases (42.7%) were diagnosed as recurrence in the CRT group and CT group, respectively. The local and regional recurrence rates in the CRT group were lower than that in the CT group (22.2% vs 24.6%, 27.8% vs 39.3%). Multivariable cox regression analysis showed that vascular invasion, nerve invasion, and adjuvant CRT were important prognostic factors for Siewert type III AGE. CONCLUSION: For locally advanced Siewert type III AGE, adjuvant CRT may prolong OS and reduce the regional recurrence rate.

7.
Can J Gastroenterol Hepatol ; 2022: 8178184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369117

RESUMO

A high Mandard score may indicate the tumor is insensitive to chemotherapy. We analyzed tumor regression and lymph node response under different Mandard scores to assess the impact of Mandard score on prognosis. Methods. Mandard scores and ypN stage of postoperative pathological reports were recorded. The results were reviewed by a professional pathologist. The radiologist compared the tumor regression before and after chemotherapy by computed tomography (CT). The survival of all patients was obtained by telephone follow-up. Multivariate Cox regression was used to assess the relationship between overall risk of death and Mandard score, imaging evaluation, and ypN stage. Results. In the Mandard score (4-5) group, the median survival time for PR and ypN0 patients was 68.5 and 76.7 months. While in the Mandard score (1-2) group, the median survival time for PD and ypN3a patients was 15.6 and 14.5 months. Imaging evaluation of tumor regression (PR 68.5 months, SD 27.8 months, and PD 10.2 months) and lymph node remission (ypN0 76.7 months, ypN1 61.6 months, ypN2 18.0 months, ypN3a 18.7 months, and ypN3b 18.3 months) showed improved survival. Mandard score, imaging evaluation, and ypN stage are important prognostic factors affecting prognosis. Conclusion. A high Mandard score does not mean neoadjuvant chemotherapy is ineffective in gastric cancer. Patients with imaging evaluation of tumor regression and ypN stage reduction may benefit from neoadjuvant chemotherapy.


Assuntos
Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Terapia Neoadjuvante/métodos , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 449-454, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35395978

RESUMO

OBJECTIVE: To investigate the evolution of blood separation results by gel extraction of multiple myeloma (MM) patients, and to evaluate the clinical value of abnormal blood separation results for the evaluation of disease and prognosis. METHODS: The clinical data of 5 patients diagnosed newly MM patients with abnormal blood separation of gel collection vessels in our hospital were retrospectively analyzed, and the changes of blood separation results and blood index levels were followed up with the improvement of treatment effect, and the correlation of different blood index levels was analyzed. RESULTS: In 5 patients with newly diagnosed MM, the blood separation result showed floating phenomenon after centrifugation, which divided into three layers and the order from top to bottom is separator gel, serum, and red blood cells(RBC). With partial remission of clinical symptoms, the blood separation results were still abnormal, which were divided into three layers from top to bottom: serum, RBC and separator gel. Finally, with complete remission of the disease, blood separation results returned to normal, from top to bottom: serum, separator gel, RBC. With the blood separation results from abnormal to normal, the blood routine indicators: Hb, Hct levels gradually increased, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) gradually decreased; biochemical indexes: TP, GLB, Ig and ß2-MG levels gradually decreased. Tumor load related indicators: serum IL-6, TNF-α, IL-17 levels gradually decreased, and IL-35 levels gradually increased; and the differences were statistically significant (P<0.05). Pearson correlation analysis showed that serum ß2-MG was positively correlated with IL-6, TNF-α and IL-17 levels (r=0.710, 0.756, 0.581, P<0.05), and negatively correlated with IL-35 level (r=-0565, P<0.05). CONCLUSION: Abnormal blood separation exists in MM patients, and there are significant differences in blood, tumor load and immune balance related indexes in patients with different blood separation results, which provides partial experimental basis for evaluation of disease, efficacy and prognosis with different blood separation results.


Assuntos
Interleucina-17 , Mieloma Múltiplo , Humanos , Interleucina-6 , Prognóstico , Estudos Retrospectivos , Fator de Necrose Tumoral alfa
9.
World J Gastrointest Surg ; 14(2): 161-173, 2022 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-35317541

RESUMO

BACKGROUND: Laparoscopic total gastrectomy (LTG) has drawn increasing attention over the years. Although LTG has shown surgical benefits compared to open TG (OTG) in early stage gastric cancer (GC), little is known about the surgical and oncological outcomes of LTG for advanced GC following neoadjuvant therapy (NAT). AIM: To compare the long- and short-term outcomes of advanced GC patients who underwent LTG vs OTG following NAT. METHODS: Advanced GC patients who underwent TG following NAT between April 2011 and May 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences were enrolled and stratified into two groups: LTG and OTG. Propensity score matching analysis was performed at a 1:1 ratio to overcome possible bias. RESULTS: In total, 185 patients were enrolled (LTG: 78; OTG: 109). Of these, 138 were paired after propensity score matching. After adjustment for propensity score matching, baseline parameters were similar between the two groups. Compared to OTG, LTG was associated with a significantly shorter length of hospital stay (P = 0.012). The rates of R0 resection, lymph node harvest, and postoperative morbidity did not significantly differ between the two groups. Overall survival (OS) outcomes were comparable between the two groups. Pathological T and N stages were found to be independent risk factors for OS. CONCLUSION: LTG can be a feasible method for advanced GC patients following NAT, as it appears to be associated with better short- and comparable long-term outcomes compared to OTG.

10.
World J Clin Cases ; 9(29): 8718-8728, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34734050

RESUMO

BACKGROUND: For advanced gastric cancer patients with pancreatic head invasion, some studies have suggested that extended multiorgan resections (EMR) improves survival. However, other reports have shown high rates of morbidity and mortality after EMR. EMR for T4b gastric cancer remains controversial. AIM: To evaluate the surgical approach for pT4b gastric cancer with pancreatic head invasion. METHODS: A total of 144 consecutive patients with gastric cancer with pancreatic head invasion were surgically treated between 2006 and 2016 at the China National Cancer Center. Gastric cancer was confirmed in 76 patients by postoperative pathology and retrospectively analyzed. The patients were divided into the gastrectomy plus en bloc pancreaticoduodenectomy group (GP group) and gastrectomy alone group (GA group) by comparing the clinicopathological features, surgical outcomes, and prognostic factors of these patients. RESULTS: There were 24 patients (16.8%) in the GP group who had significantly larger lesions (P < 0.001), a higher incidence of advanced N stage (P = 0.030), and less neoadjuvant chemotherapy (P < 0.001) than the GA group had. Postoperative morbidity (33.3% vs 15.3%, P = 0.128) and mortality (4.2% vs 4.8%, P = 1.000) were not significantly different in the GP and GA groups. The overall 3-year survival rate of the patients in the GP group was significantly longer than that in the GA group (47.6%, median 30.3 mo vs 20.4%, median 22.8 mo, P = 0.010). Multivariate analysis identified neoadjuvant chemotherapy [hazard ratio (HR) 0.290, 95% confidence interval (CI): 0.103-0.821, P = 0.020], linitis plastic (HR 2.614, 95% CI: 1.024-6.675, P = 0.033), surgical margin (HR 0.274, 95% CI: 0.102-0.738, P = 0.010), N stage (HR 3.489, 95% CI: 1.334-9.120, P = 0.011), and postoperative chemoradiotherapy (HR 0.369, 95% CI: 0.163-0.836, P = 0.017) as independent predictors of survival in patients with pT4b gastric cancer and pancreatic head invasion. CONCLUSION: Curative resection of the invaded pancreas should be performed to improve survival in selected patients. Invasion of the pancreatic head is not a contraindication for surgery.

11.
World J Gastrointest Oncol ; 13(3): 161-173, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33738044

RESUMO

BACKGROUND: The association between body mass index (BMI) and clinical outcomes remains unclear among patients with resectable gastric cancer. AIM: To investigate the relationship between BMI and long-term survival of gastric cancer patients. METHODS: This retrospective study included 2526 patients who underwent radical gastrectomy for gastric cancer between September 2013 and June 2018. The patients were divided into four groups: Group A (low BMI, < 18.5 kg/m2), group B (normal BMI, 18.5-24.9 kg/m2), group C (overweight, 25-29.9 kg/m2), and group D (obese, ≥ 30 kg/m2). Clinicopathological findings and survival outcomes were recorded and analyzed. RESULTS: Preoperative weight loss was more common in the low-BMI group, while diabetes was more common in the obese group. Upper-third gastric cancer accounted for a large proportion of cases in the higher BMI groups. Major perioperative complications tended to increase with BMI. The 5-year overall survival rates were 66.4% for group A, 75.0% for group B, 77.1% for group C, and 78.6% for group D. The 5-year overall survival rate was significantly lower in group A than in group C (P = 0.008) or group D (P = 0.031). Relative to a normal BMI value, a BMI of < 18.5 kg/m2 was associated with poor survival (hazard ratio: 1.558, 95% confidence interval: 1.125-2.158, P = 0.008). CONCLUSION: Low BMI, but not high BMI, independently predicted poor survival in patients with resectable gastric cancer.

12.
World J Clin Cases ; 8(21): 5099-5103, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33269246

RESUMO

The coronavirus disease 2019 pandemic has become a major global public health problem. Governments are taking the necessary steps to reduce the movement of people to contain the spread of the virus. However, these measures have caused considerable distress to patients with gastric cancer who are newly diagnosed or are undergoing treatment. In addition to the cancer, they must deal with longer waiting times for surgery and poor communication with doctors. Furthermore, gastric cancer patients generally have low immunity and a poor nutritional status, so they are a high-risk group for infection with the novel coronavirus. Therefore, it is necessary to formulate reasonable outpatient management strategies to reduce the adverse effects of the pandemic on their treatment. We summarize the management strategies for patients with gastric cancer during the pandemic.

13.
World J Clin Cases ; 8(21): 5353-5360, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33269270

RESUMO

BACKGROUND: Afferent loop syndrome (ALS) is a rare mechanical complication that occurs after reconstruction of the stomach or esophagus to the jejunum, such as Billroth II gastrojejunostomy, Roux-en-Y gastrojejunostomy, or Roux-en-Y esophagoje-junostomy. Traditionally, an operation is the first choice for benign causes. However, for patients in poor physical condition who experience ALS soon after R0 resection, the type of treatment remains controversial. Here, we present an efficient conservative method to treat ALS. CASE SUMMARY: Case 1 was a 69-year-old male patient who underwent total gastrectomy with Roux-en-Y jejunojejunostomy. On postoperative day (POD) 10 he developed symptoms of ALS that persisted and increased over 1 wk. Case 2 was a 59-year-old male patient who underwent distal gastrectomy with Billroth II gastrojejunostomy. On postoperative day POD 9 he developed symptoms of ALS that persisted for 2 wk. Both patients underwent fluoroscopic-guided nasointestinal tube placement with maintenance of continuous negative pressure suction. Approximately 20 d after the procedure, both patients had recovered well and were discharged from hospital after removal of the tube. At 3-mo follow-up, there were no signs of ALS in these two patients. CONCLUSION: This is the first report of treating postoperative ALS by fluoroscopic-guided nasointestinal tube placement. Our cases demonstrate that this procedure is an effective and safe method to treat ALS that relieves patients' symptoms and avoids complications caused by other invasive procedures.

14.
Front Immunol ; 11: 1253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719674

RESUMO

Opioid abuse alters the functions of immune cells in both in vitro and in vivo systems, including macrophages. Here, we investigated the effects of methadone, a widely used opioid receptor agonist for treatment of opiate addiction, on the expression of intracellular viral restriction factors and HIV replication in primary human macrophages. We showed that methadone enhanced the HIV infectivity in primary human macrophages. Mechanistically, methadone treatment of macrophages reduced the expression of interferons (IFN-ß and IFN-λ2) and the IFN-stimulated anti-HIV genes (APOBEC3F/G and MxB). In addition, methadone-treated macrophages showed lower levels of several anti-HIV microRNAs (miRNA-28, miR-125b, miR-150, and miR-155) compared to untreated cells. Exogenous IFN-ß treatment restored the methadone-induced reduction in the expression of the above genes. These effects of methadone on HIV and the antiviral factors were antagonized by pretreatment of cells with naltrexone. These findings provide additional evidence to support further studies on the role of opiates, including methadone, in the immunopathogenesis of HIV disease.


Assuntos
Infecções por HIV/imunologia , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/virologia , Metadona/farmacologia , Biomarcadores , Células Cultivadas , Quimiocina CCL4/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/metabolismo , HIV-1/imunologia , Humanos , Interferons/genética , Interferons/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , MicroRNAs/genética , RNA Viral , Replicação Viral/efeitos dos fármacos
15.
Front Immunol ; 11: 1072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636833

RESUMO

Hantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and have led to public health threat in China. The pathogenesis of HFRS is complex and involves capillary leakage due to the infection of vascular endothelial cells. Accumulating evidence has demonstrated that hantavirus can induce apoptosis in many cells, but the mechanism remains unclear. Our studies showed that Hantaan virus (HTNV) infection could induce TNF-related apoptosis-inducing ligand (TRAIL) expression in primary human umbilical vein endothelial cells (HUVECs) and sensitize host cells toward TRAIL-mediated apoptosis. Furthermore, TRAIL interference could inhibit apoptosis and enhance the production of HTNV as well as reduce IFN-ß production, while exogenous TRAIL treatment showed reverse outcome: enhanced apoptosis and IFN-ß production as well as a lower level of viral replication. We also observed that nucleocapsid protein (NP) and glycoprotein (GP) of HTNV could promote the transcriptions of TRAIL and its receptors. Thus, TRAIL was upregulated by HTNV infection and then exhibited significant antiviral activities in vitro, and it was further confirmed in the HTNV-infected suckling mice model that TRAIL treatment significantly reduced viral load, alleviated virus-induced tissue lesions, increased apoptotic cells, and decreased the mortality. In conclusion, these results demonstrate that TRAIL-dependent apoptosis and IFN-ß production could suppress HTNV replication and TRAIL treatment might be a novel therapeutic target for HTNV infection.


Assuntos
Apoptose/imunologia , Vírus Hantaan/imunologia , Vírus Hantaan/patogenicidade , Interações entre Hospedeiro e Microrganismos/imunologia , Ligante Indutor de Apoptose Relacionado a TNF/imunologia , Animais , Animais Lactentes , Modelos Animais de Doenças , Feminino , Febre Hemorrágica com Síndrome Renal/imunologia , Febre Hemorrágica com Síndrome Renal/terapia , Febre Hemorrágica com Síndrome Renal/virologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Interferon beta/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Gravidez , RNA Interferente Pequeno/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/uso terapêutico , Carga Viral/imunologia , Replicação Viral
16.
Fitoterapia ; 143: 104599, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32330576

RESUMO

One novel polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid metabolite, laricinin A (1), two new meroterpenoids, tricycloalternarenes X and Y (2 and 3), one new coumarin, 3,4,7-trihydroxy-6-methylcoumarin (4), together with the known ethyl acetylorsellinate (5), diorcinol K (6), and tricycloalternarenes C and D (7 and 8) were obtained from culture of the fungus Botrysphaeria laricina isolated from the moss Rhodobryum umgiganteum. The structures of the new compounds were elucidated based on extensive spectroscopic techniques including HRMS and 1D and 2D NMR measurements. The absolute configuration of compound 1 was determined by ECD calculation and it was the first example of a novel group of PKS-NRPS hybrids possessing an unprecedented methyldihydropyran-isobutylpyrrolidinone skeleton. Compounds 2, 7, and 8 showed significant quinone reductase inducing activity in Hepa 1c1c7 cells.


Assuntos
Ascomicetos/química , Produtos Biológicos/farmacologia , Terpenos/farmacologia , Animais , Produtos Biológicos/isolamento & purificação , Briófitas/microbiologia , Linhagem Celular Tumoral , China , Camundongos , Estrutura Molecular , Peptídeo Sintases/metabolismo , Policetídeo Sintases/metabolismo , Metabolismo Secundário , Terpenos/isolamento & purificação
17.
Fitoterapia ; 142: 104498, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32058053

RESUMO

Three new triterpenoids, mallomacrostins A-C (1-3), and 11 known ones (4-14) were obtained from the twigs and leaves of Mallotus macrostachyus. Mallomacrostin A possessed a new trinor-D:B-friedobaccharane skeleton. The structures of the new compounds were elucidated on the basis of extensive spectroscopic techniques including HR-ESIMS and NMR and the structure of 1 was confirmed by single crystal X-ray diffraction analysis. Spectroscopic data of the known compound 4 were provided for the first time. Compounds 2 and 10 exhibited significant anti-inflammatory activity by inhibiting LPS-induced release of nitric oxide with IC50 of 70.0 µM and 14.0 µM, respectively.


Assuntos
Mallotus (Planta)/química , Triterpenos/química , Triterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Camundongos , Modelos Moleculares , Estrutura Molecular , Folhas de Planta/química , Células RAW 264.7
18.
Ther Clin Risk Manag ; 14: 1975-1986, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349276

RESUMO

PURPOSE: The effect of glucocorticoid(s) on connective tissue disease (CTD)-related interstitial lung disease (ILD) is controversial. This multicenter study aimed to identify glucocorticoid-sensitive patients using a radiomics approach. METHODS: A total of 416 CTD-ILD patients who began glucocorticoid treatment at the discretion of the attending physician, with or without cyclophosphamide, were included in this study. High doses were defined as pulsed intravenous methylprednisolone, an initial dose of 1 mg/kg/day of prednisolone or 0.8 mg/kg/day of methylprednisolone. Low doses were defined as those less than high doses. Radiomics features were manually extracted from primary lung lesions delineated on computed tomography images, and selected by variance, univariate feature selection, and least absolute shrinkage and selection operator regression model. The prediction models were developed using data from 309 patients from two centers and externally validated in 107 patients from four other hospitals. RESULTS: Treatment response in the training and validation groups was 38.5% and 36.4%, respectively. Eleven radiomics features were selected from 1,029 features with predictive value. Random forest models built for radiomics features to predict treatment response yielded a sensitivity of 0.897. The calibration curve of a nomogram demonstrated good agreement between prediction and observation. Decision curve analysis indicated that glucocorticoid was beneficial if the predicted response rate was 50%-60% for an individual. High doses of glucocorticoids and cyclophosphamide yielded superior efficacy. CONCLUSION: Radiomics-based predictive models reliably identified glucocorticoid-sensitive CTD-ILD patients. Short-term, high-dose glucocorticoid with cyclophosphamide yielded promising results as a potential therapy.

19.
Cell Physiol Biochem ; 47(4): 1630-1642, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29949792

RESUMO

BACKGROUND/AIMS: Pterygium is a common ocular surface disease with an unknown etiology and threatens vision as it invades into the cornea. Circular RNAs (circRNAs) are a novel class of RNA transcripts that participate in several physiological and pathological processes. However, the role of circRNAs in pathogenesis of pterygium remains largely unknown. METHODS: Genome-wide circRNA expression profiling was performed to identify pterygium -related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was performed to predict the function of differentially expressed circRNAs in pterygium. MTT assays, Ki67 staining, Transwell assay, Hoechst 33342 staining, and Calcein-AM/PI staining were performed to determine the effect of circRNA silencing on pterygium fibroblast and epithelial cell function. RESULTS: Approximately 669 circRNAs were identified to be abnormally expressed in pterygium tissues. GO analysis demonstrated that the host genes of differentially expressed circRNAs were targeted to extracellular matrix organization (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis showed that dysregulated circRNAs-mediated regulatory networks were mostly enriched in focal adhesion signaling pathway. Notably, circ_0085020 (circ-LAPTM4B) was shown as a potential biomarker for pterygium. circ_0085020 (circ-LAPTM4B) silencing affected the viability, proliferation, migration, and apoptosis of pterygium fibroblast and epithelial cells in vitro. CONCLUSIONS: This study provides evidence that circRNAs are involved in the pathogenesis of pterygium and might constitute promising targets for the therapeutic intervention of pterygium.


Assuntos
Células Epiteliais , Fibroblastos , Estudo de Associação Genômica Ampla , Pterígio , RNA , Biomarcadores/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Pterígio/genética , Pterígio/metabolismo , Pterígio/patologia , RNA/biossíntese , RNA/genética
20.
Biochem Biophys Res Commun ; 496(4): 1236-1242, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29409883

RESUMO

Excessive light exposure leads to retinal degeneration and accelerates the progression and severity of several ocular diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa. Long non-coding RNAs (LncRNAs) have emerged as important regulators of photoreceptor development and ocular diseases. In this study, we investigated the role of lncRNA-MEG3 in light-induced retinal degeneration. MEG3 expression was significantly up-regulated after light insult in vivo and in vitro. MEG3 silencing protected against light-induced retinal degeneration in vivo and light-induced photoreceptor cell apoptosis in vitro. Mechanistically, MEG3 regulated retinal photoreceptor cell function by acting as p53 decoy. MEG3 silencing decreased caspase 3/7 activity, up-regulated anti-apoptotic protein (Bcl-2) expression, and down-regulated pro-apoptotic protein (Bax) expression. Taken together, this study provides a promising method of MEG3 silencing for treating light-induced retinal degeneration.


Assuntos
Terapia Genética/métodos , RNA Longo não Codificante/genética , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/prevenção & controle , Degeneração Retiniana/genética , Degeneração Retiniana/prevenção & controle , Animais , Inativação Gênica , Luz/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Lesões Experimentais por Radiação/patologia , Degeneração Retiniana/patologia , Resultado do Tratamento
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