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1.
Int Immunopharmacol ; 132: 112024, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608475

RESUMO

Ulcerative colitis (UC) is a recurrent intestinal disease with an increasing incidence worldwide that seriously affects the life of patients. Turtle peptide (TP) is a bioactive peptide extracted from turtles that has anti-inflammatory, antioxidant and anti-aging properties. However, studies investigating the effect of TP on the progression of UC are lacking. The aim of this study was to investigate effects and underlying mechanisms of TP and its derivative peptide GPAGPIGPV (GP-9) in alleviating UC in mice. The results showed that 500 mg/kg TP treatment significantly ameliorated colitis symptoms and oxidative stress in UC mice. TP alleviated intestinal barrier damage in UC mice by promoting mucosal repair and increasing the expression of tight junction proteins (ZO1, occludin and claudin-1). TP also modulated the composition of the gut microbiota by increasing the abundance of the beneficial bacteria Anaerotignum, Prevotellaceae_UCG-001, Alistipes, and Lachno-spiraceae_NK4A136_group and decreasing the abundance of the harmful bacteria Prevotella_9 and Parasutterella. Furthermore, we characterized the peptide composition of TP and found that GP-9 ameliorated the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by inhibiting the TLR4/NF-κB signaling pathway. In conclusion, TP and its derivative peptides ameliorated DSS-induced ulcerative colitis by inhibiting the expression of inflammatory factors and modulating the composition of the intestinal microbiota; this study provides a theoretical basis for the application of TP and its derivative peptides for their anti-inflammatory activity.

2.
Int J Surg ; 109(12): 4009-4017, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37678274

RESUMO

BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.


Assuntos
Atresia Biliar , Colangite , Icterícia , Criança , Humanos , Lactente , Portoenterostomia Hepática/efeitos adversos , Estudos Prospectivos , Imunoglobulinas Intravenosas , Atresia Biliar/cirurgia , Atresia Biliar/complicações , Colangite/tratamento farmacológico , Colangite/etiologia , Icterícia/complicações , Antibacterianos/uso terapêutico , Meropeném , Estudos Retrospectivos , Resultado do Tratamento
3.
PeerJ ; 11: e15441, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304872

RESUMO

Background: Cisplatin (CDDP) is of importance in cancer treatment and widely used in advanced gastric cancer (GC). However, its clinical usage is limited due to its resistance, and the regulatory mechanism of CDDP resistance in GC has not yet been fully elucidated. In this study, we first conducted a comprehensive study to investigate the role of MFAP2 through bioinformatics analysis. Methods: The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were applied to downloadgene expression data and clinicopathologic data, and the differentially expressed genes (DEGs) were further analyzed. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and survival analysis were conducted. Furthermore, according to the clinicopathological characteristics of TCGA, clinical correlation analysis was conducted, and a receiver operating characteristic curve (ROC) was plotted. Results: We revealed that FAP, INHBA and MFAP2 were good diagnostic factors of GC. However, the mechanism of MFAP2 in GC remains elusive, especially in the aspect of chemotherapy resistance. We developed the CDDP-resistant cell line, and found that MFAP2 was upregulated in CDDP-resistant cells, and MFAP2-knockdown improved CDDP sensitivity. Finally, we found that MFAP2 enhanced CDDP resistance by inducing autophagy in drug-resistant cell lines. Conclusions: The above results suggested that MFAP2 could affect the chemotherapy resistance by altering the level of autophagy in GC patients as a potential therapeutic target.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Cisplatino/farmacologia , Autofagia/genética , Linhagem Celular
4.
Asian J Androl ; 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36930541

RESUMO

This study aimed to determine whether the abnormal deep layer of dartos fascia plays an important role in buried penis. Forty-nine patients with buried penis were treated with anatomical resection of the deep layer of dartos fascia under a microscope. Penile length was measured before and after completely resecting the deep layer to investigate the role of this layer in penile retraction. The superficial and deep layers of dartos fascia were collected from 49 patients with buried penis, the normal superficial layers were collected from 25 children/adults who underwent circumcision for nonmedical reasons, and the normal deep layers were collected from 20 adult cadavers. The penile fascia samples were stained with hematoxylin-eosin, Masson's trichrome, Sirius red, and Verhoeff's Van Gieson, and subjected to immunohistochemical examination and scanning electron microscopy. The penile shaft (mean ± standard deviation) was found to be significantly elongated after resecting the deep layer compared with that before resection (6.8 ± 1.9 cm vs 6.0 ± 1.6 cm, P < 0.001). An abnormal deep layer of dartos fascia characterized by disordered and fragmented elastic fibers was observed in 87.8% (43/49) of buried penis samples, whereas no abnormal deep layer was observed in normal penises from cadavers (0/20, P < 0.001). Thus, the abnormal deep layer of dartos fascia plays an important role in the buried penis. Its resection is helpful for avoiding recurrence.

5.
Surg Endosc ; 37(2): 1173-1180, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36149506

RESUMO

BACKGROUND: Portal vein tumor thrombosis (PVTT) secondary to primary liver carcinoma (PLC) is commonly associated with poor prognosis and poses great challenge. This study was to evaluate the efficacy and safety of percutaneous endovascular radiofrequency ablation (RFA) in treatment of PVTT. METHODS: Consecutive patients who were performed endovascular RFA because of PVTT in single-institution in recent 8 years were retrospectively reviewed, compared with patients who underwent only sequential transcatheter arterial chemoembolization (TACE) during the contemporary period. Patency of portal vein, complications, and overall survival (OS) were investigated. RESULTS: One hundred and 20 patients who underwent endovascular RFA and 96 patients who underwent only sequential TACE were included. No severe complications happened in both groups. Except the higher rates of severe fever and moderate pain in the study group, no difference was found in the incidence of side effects and complications. The effective rate in the study group was (78.3%, 94/120) significantly higher than the comparison group (35.4%, 34/96). The median survival time and 1-3 years cumulative survival rates in the study group were 15.7 months and 42.5%, 21.7%, 2.5%, respectively, and 11.3 months, 21.9%, 9.4%, 0 correspondingly in the comparison group, without significant difference. Type of PVTT and Child-Pugh classification of liver function were independent risk factors, and OS was significantly improved by endovascular RFA and subsequent therapy. CONCLUSION: Endovascular RFA is technically safe and feasible for unresectable PLC and PVTT to improve the prognosis and quality of life.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Ablação por Radiofrequência , Trombose , Trombose Venosa , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Veia Porta/patologia , Estudos Retrospectivos , Qualidade de Vida , Resultado do Tratamento , Trombose/complicações , Terapia Combinada
6.
Phys Rev Lett ; 129(15): 151101, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36269963

RESUMO

Interacting massive spin-1 fields have been widely used in cosmology and particle physics. We obtain a new condition on the validity of the classical limit of these theories related to the nontrivial constraints that exist for vector field components. A violation of this consistency condition causes a singularity in the time derivative of the auxiliary component and could impact, for example, the field's cosmic history and superradiance around black holes. We show that gauge-invariant interactions are generally safe from this problem, even though the mass term explicitly breaks the gauge symmetry. Such restrictions for interactions are expected to exist generically in many other nontrivially constrained systems.

7.
Oncol Lett ; 23(1): 37, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34966453

RESUMO

Mucin 13 (MUC13) is a glycoprotein that is expressed on the cell surface and participates in the tumorigenesis of multiple malignancies, including pancreatic cancer, colorectal cancer and renal cancer. However, to the best of our knowledge, the expression levels and function of MUC13 in lung cancer progression have not yet been demonstrated. Therefore, the present study examined the expression pattern and regulatory role of MUC13 in lung cancer tumorigenesis. The results demonstrated that MUC13 was highly expressed in lung cancer tissues and cell lines compared with that in normal tissues and cell lines. Functionally, knockdown of MUC13 inhibited cell proliferation and enhanced the apoptosis of A549 and NCI-H1650 lung cancer cells. Furthermore, silencing of MUC13 suppressed the migration and invasion of lung cancer cells. Additionally, a xenograft tumor model demonstrated that knockdown of MUC13 delayed the development of the lung cancer xenograft and suppressed the expression of proliferation marker Ki-67 in tumor tissues. Mechanistically, MUC13 activated the ERK signaling pathway by enhancing the phosphorylation of ERK, JNK and p38 in lung cancer tissues compared with that in normal tissues. Knockdown of MUC13 inhibited the phosphorylation of ERK/JNK/p38 in A549 and NCI-H1650 cells. Overall, these findings suggested that MUC13 could act as an oncogenic glycoprotein to accelerate the progression of lung cancer via abnormal activation of the ERK/JNK/p38 signaling pathway and might serve as a therapeutic target for lung cancer treatment.

8.
Surg Endosc ; 36(3): 1789-1798, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33788032

RESUMO

BACKGROUND: Although self-expandable mental stents (SEMS) placement is the standard care for relieving obstructive jaundice caused by unresectable malignant biliary stricture, how to maintain stent potency remains an intractable problem. This study was to evaluate the efficacy and safety of endobiliary radiofrequency ablation (RFA) through percutaneous transhepatic cholangiography (PTC) pathway in treating such patients. METHODS: Consecutive patients who were performed endobiliary RFA as well as SEMS placement because of unresectable malignant obstructive jaundice in single institution in recent 8 years were retrospectively reviewed. As comparison, patients who underwent only percutaneous SEMS placement for unresectable malignant biliary stricture during the contemporary period were reviewed. Stent patency, complications, complications, and overall survival (OS) were investigated and analyzed. RESULTS: One hundred and fifty patients who underwent endobiliary RFA and 127 patients who underwent only stent placement were included in this study. In the study group of endobiliary RFA, 87 patients (58.0%) underwent ablation for 1 time, 49 (32.7%) for 2 times, and 14 (9.3%) for 3 times. Complications related to RFA as well as SEMS placement happened in 113 patients (75.3%), without severe complications that needed emergent surgery or interventional therapy. The median duration of stent patency after ablation was 11.2 month, and the median survival time was 12.3 month. As comparison, difference was found in the number of interventional procedures and stents placed, duration of initial stent patency, and the incidence of moderate bleeding and pain. In the study group, only the type of tumor that caused biliary obstruction (intrahepatic carcinoma vs. extrahepatic carcinoma) was a poor independent factor (P = 0.035) for recurrent biliary obstruction. Repeated interventional therapy and adoption of subsequent therapy were only independent factors for OS. CONCLUSIONS: Endobiliary RFA and SEMS placement is technically safe and feasible for unresectable malignant obstructive jaundice to improve the quality of life and prolong survival.


Assuntos
Neoplasias dos Ductos Biliares , Ablação por Cateter , Colestase , Icterícia Obstrutiva , Ablação por Radiofrequência , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Ablação por Cateter/métodos , Colestase/etiologia , Colestase/cirurgia , Humanos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/cirurgia , Qualidade de Vida , Ablação por Radiofrequência/efeitos adversos , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento
9.
Zhongguo Zhong Yao Za Zhi ; 46(21): 5560-5567, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951207

RESUMO

The terpenoids in Pogostemon cablin have complex structures and abundant pharmacological effects. Patchouli alcohol(PA) and pogostone(PO) have a high medicinal value by virtue of anti-tumor, anti-inflammatory, antibacterial, antioxidant, and other biological activities. Due to the low content of terpenoid metabolites in P. cablin, the study of biosynthesis and metabolism regulation can provide a biosynthetic basis for obtaining high-content terpenoids. In this study, key enzyme genes in biosynthesis, transcription factors in metabolism regulation, spatio-temporal expression of terpene synthase were reviewed, aiming to provide a reference for the development, protection, and utilization of P. cablin resources.


Assuntos
Pogostemon , Pogostemon/genética , Terpenos , Fatores de Transcrição/genética
10.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4117-4123, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467722

RESUMO

This study aims to explore the relationship of DNA methylation with the contents of the index components as well as the growth and development of Pogostemon cablin. The demethylation reagent 5-azacytidine(5-azaC) was used to treat the tissue culture seedlings of patchouliol-type P. cablin. High performance liquid chromatography was employed to evaluate the changes of DNA methy-lation in P. cablin, and GC-MS to detect the contents of index components in P.cablin. The agronomic characters of P.cablin were measured using the common methods. The results showcased that DNA methylation of P.cablin was significantly reduced by 5-azaC in a concentration-dependent manner. Thirty days after treatment with 5-azaC at different concentrations, the content of patchouli alcohol changed slightly; compared with that in the control group, the content of pogostone in 50 µmol·L~(-1) and 100 µmol·L~(-1) 5-azaC groups was significantly up-regulated. The 100 µmol·L~(-1) 5-azaC group had the largest differences in contents of pogostone and patchouli alcohol compared with the control group, followed by the 50 µmol·L~(-1) 5-azaC group. Ninety days after disinhibition, the content of pogostone in the treatment group was significantly increased and the content of patchouli alcohol was significantly decreased. In addition, 5-azaC significantly inhibited the growth and development of P.cablin in a dose-dependent manner. These results indicate that DNA methylation regulates the biosynthesis of the index components in patchouliol-type P.cablin and proper demethylation can directly promote the synthesis of pogostone and indirectly affect the accumulation of patchouli alcohol.


Assuntos
Pogostemon , Azacitidina , Metilação de DNA , Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis , Pogostemon/genética
11.
Yonsei Med J ; 62(10): 918-927, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34558871

RESUMO

PURPOSE: We compared the clinical outcomes of modified procedures for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) based on a risk-reduced strategy with those of classic ALPPS procedures in treating large liver carcinoma. MATERIALS AND METHODS: Short-term outcomes, increases in future liver remnant (FLR) and functional FLR (FFLR), and overall survival (OS) were compared between 45 consecutive patients treated with modified ALPPS procedures and 34 patients treated with classic ALPPS procedures. RESULTS: Clinical outcomes after the 1st-stage operation markedly improved with the modified procedures. Although the proportions of liver cirrhosis and hepatocellular carcinoma were higher in the modified group, the mortality and incidence of severe complications did not increase. FLR and FFLR hypertrophy at 1 week after the 1st-stage operation were similar in both groups; however, kinetic growth rates in the modified group were lower. OS rates were similar. CONCLUSION: Modified ALPPS procedures could be safely applied to provide long-term survival for patients with liver cirrhosis without sufficient FLR.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Ligadura , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia
12.
Aging (Albany NY) ; 13(13): 17155-17176, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34081626

RESUMO

Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Hipóxia/complicações , MicroRNAs/genética , Fatores de Processamento de RNA/genética , RNA Longo não Codificante/genética , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Neoplasias Esofágicas/mortalidade , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Nus , Valor Preditivo dos Testes , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
13.
World J Clin Cases ; 9(8): 1793-1802, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33748228

RESUMO

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication and a leading cause of death after hepatectomy, an accurate prediction of PHLF is important for improvement of prognosis after hepatectomy. AIM: To retrospectively analyze the risk factors for postoperative liver failure in patients undergoing hepatectomy for liver tumors. METHODS: The clinical data of 80 patients undergoing hepatectomy in our hospital from June 2018 to January 2020 were collected. With laboratory examination as well as pre- and post-operative abdominal three-dimensional reconstructive computed tomography, the demographic data, surgical data, biochemical indicators, coagulation index, routine blood tests, spleen and liver volumes, relative remnant liver volume, and other related indicators were obtained and compared between patients with PHLF and those without PHLF. RESULTS: PHLF occurred in 19 (23.75%) patients. Univariate logistic regression analysis showed that gender, history of hepatitis/cirrhosis, and preoperative bilirubin, albumin, coagulation function, albumin-bilirubin ratio, aspartate amino-transferase-to-platelet ratio index (APRI), Model for End-Stage Liver Disease score, spleen volume (SV), spleen volume/liver volume ratio (SV/LV), and relative remnant liver volume were statistically associated with the occurrence of PHLF (all P < 0.05). Multivariate regression analysis showed that preoperative total bilirubin, platelets (PLT), APRI, and SV/LV were independent risk factors for PHLF (all P < 0.05). The area under the curve and cut-off values were 0.787 and 18.6 mmol/L for total bilirubin, 0.893 and 146 × 1012/L for PLT, 0.907 and 0.416 for APRI, and 0.752 and 20.84% for SV/LV, respectively. CONCLUSION: For patients undergoing liver resection, preoperative total bilirubin, PLT, APRI, and SV/LV are independent risk factors for PHLF. These findings may provide guidance to safely perform liver surgery in such patients.

14.
World J Clin Cases ; 9(3): 644-650, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33553403

RESUMO

BACKGROUND: Cervical spondylectomy for the treatment of cervical tumors is traumatic, causes bleeding, and is risky. This study reports on the experience with minimally invasive cervical spondylectomy for a cervical metastasis and reviewed the literature on cervical spondylectomy. The purpose was to reduce the risk and trauma of spondylectomy. CASE SUMMARY: A 60-year-old woman presented with cervical pain and radiating pain in the left upper limb for more than 2 mo. Preoperative diagnosis was C4 metastasis of thyroid cancer. Preoperative visual analogue scale score was 5. American Spinal Cord Injury Association (ASIA) grade was E. Tomita classification was 7. Weinstein-Boriani-Biagini (WBB) classification was A-D, 3-9. Tomita score was 5. Modified Tokuhashi score was 9. Spinal instability neoplastic score (SINS) was 13. The patient underwent minimally invasive cervical spondylectomy on September 28, 2017. The operative time was 200 min; the estimated blood loss was 1200 mL. The operation was successful, without complications. The postoperative visual analogue scale score was 0. The patient remained classified as ASIA grade E at the last follow-up. She accepted regular iodine-131 therapy postoperatively. The serum thyroglobulin (Tg) level of this patient was 299.02 ng/mL at 1 mo after the operation and was 13.57 ng/mL at the last follow-up. There was no local recurrence at the 25-mo follow-up, according to images, single-photon emission computed tomography, and serum Tg levels. Obvious ossification and solid fusion of C3-C5 were found at the last follow-up. CONCLUSION: Minimally invasive cervical spondylectomy with tubular retractor could minimize soft tissue trauma, intraoperative traction injury, and paraspinal muscle injury, accelerating postoperative recovery. This technique requires a rich experience in cervical spine surgery with tubular retractors, so that surgeons can visualize the anatomical structure in a small field.

15.
J Pediatr Surg ; 55(11): 2308-2316, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32321629

RESUMO

PURPOSE: To investigate the effects of low dose endotoxin on transcriptional activity in intestinal epithelium, and its role in necrotizing enterocolitis (NEC). METHODS: Lipopolysaccharides (LPS) were injected into the amniotic cavity of pregnant mice under ultrasound guidance. The effects of LPS on fetal and neonatal intestines were determined. Mouse pups were exposed to low dose LPS (0.01 µg per fetus) prenatally and subjected to experimental NEC after birth. The incidence and severity of NEC, as well as intestinal permeability, NF-κB activation, and IL-6 expression were studied. The signaling pathways in the intestinal epithelial cells (IECs) that were activated by LPS were also investigated. RESULTS: Low dose LPS did not increase apoptosis, myeloperoxidase activity, histological injury or NF-κB activity in fetal intestines. However, prenatal low dose LPS exposure disturbed the transient and self-limited activation of NF-κB in neonatal intestines after birth. Importantly, it increased the incidence and severity of experimental NEC in neonatal mice. In primary IECs, low dose LPS induced IRAK-1 expression via activation of GSK3ß. Elevated IRAK-1 levels prolonged the activation of IECs upon stimulation by high dose LPS. CONCLUSION: Prenatal low dose endotoxin exposure disturbs self-limited postnatal epithelial cell activation and predisposes the neonatal intestine to NEC. LEVEL OF EVIDENCE: Not applicable (experimental animal study).


Assuntos
Endotoxinas/toxicidade , Enterocolite Necrosante , Células Epiteliais/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Enterocolite Necrosante/induzido quimicamente , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/fisiopatologia , Intestinos/citologia , Lipopolissacarídeos , Camundongos , NF-kappa B/metabolismo , Gravidez
16.
Pediatr Surg Int ; 36(1): 81-91, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31541279

RESUMO

PURPOSE: The roles of commensal bacteria after intestinal ischemia and reperfusion (IIR) are unclear. In current study, we aim to investigate the effects and underlying mechanisms of commensal bacteria in injury and epithelial restitution after IIR. METHODS: Commensal gut bacteria were deleted by broad-spectrum antibiotics in mice. IIR was induced by clamping superior mesenteric artery. Intestinal injury, permeability, epithelial proliferation, and proinflammatory activity of mesenteric lymph were investigated. RESULTS: Commensals deletion improved mice survival in the early phase, but failed to improve the overall survival at 96 h after IIR. Commensals deletion reduced proliferation of intestinal epithelial cells (IEC) and augmented proinflammatory activity of mesenteric lymph after IIR. Lipopolysaccharides (LPS) supplement promoted IEC proliferation and improved survival in mice with commensals deletion after IIR. LPS induced production of prostaglandin E2 (PGE2) in mucosa via toll-like receptor 4-NFκB-cyclooxygenase 2 pathway. PGE2 enhanced IEC proliferation in vivo, which was preceded by activation of Akt and extracellular signal-regulated kinase (ERK) 1/2. Blocking of EGFR, PI3K/Akt activity abolished LPS-induced IEC proliferation. CONCLUSIONS: Commensal bacteria are essential for epithelial restitution after IIR, which enhance IEC proliferation via induction of PGE2.


Assuntos
Intestinos/microbiologia , Isquemia/microbiologia , Traumatismo por Reperfusão/microbiologia , Animais , Antibacterianos/farmacologia , Proliferação de Células , Dinoprostona/metabolismo , Células Epiteliais/fisiologia , Mucosa Intestinal/metabolismo , Intestinos/irrigação sanguínea , Intestinos/citologia , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismo por Reperfusão/metabolismo
17.
World J Gastroenterol ; 25(3): 346-355, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30686902

RESUMO

BACKGROUND: Exposure to high sustained +Gz (head-to-foot inertial load) is known to have harmful effects on pilots' body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the precise cause has not been well defined. AIM: To investigate rat liver function changes in response to repeated +Gz exposure. METHODS: Ninety male Wistar rats were randomly divided into a blank control group (BC group, n = 30), a +6 Gz/5 min stress group (6GS group, n = 30), and a +10 Gz/5min stress group (10GS group, n = 30). The 6GS and 10GS groups were exposed to +6 Gz and +10 Gz, respectively, in an animal centrifuge. The onset rate of +Gz was 0.5 G/s. The sustained time at peak +Gz was 5 min for each exposure (for 5 exposures, and 5-min intervals between exposures for a total exposure and non-exposure time of 50 min). We assessed liver injury by measuring the portal venous flow volume, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver tissue malondialdehyde (MDA), Na+-K+-ATPase, and changes in liver histology. These parameters were recorded at 0 h, 6 h, and 24 h after repeated +Gz exposures. RESULTS: After repeated +Gz exposures in the 6GS and the 10GS groups, the velocity and flow signal in the portal vein (PV) were significantly decreased as compared to the BC group at 0 h after exposure. Meanwhile, we found that the PV diameter did not change significantly. However, rats in the 6GS group had a much higher portal venous flow volume than the 10GS group at 0 h after exposure. The 6GS group had significantly lower ALT, AST, and MDA values than the 10GS group 0 h and 6 h post exposure. The Na+-K+-ATPase activity in the 6GS group was significantly higher than that in the 10GS group 0 h and 6 h post exposure. Hepatocyte injury, determined pathologically, was significantly lower in the 6GS group than in the 10GS group. CONCLUSION: Repeated +Gz exposures transiently cause hepatocyte injury and affect liver metabolism and morphological structure.


Assuntos
Aceleração/efeitos adversos , Hipergravidade/efeitos adversos , Hepatopatias/fisiopatologia , Fígado/lesões , Estresse Fisiológico , Medicina Aeroespacial , Animais , Velocidade do Fluxo Sanguíneo , Centrifugação/efeitos adversos , Modelos Animais de Doenças , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/irrigação sanguínea , Fígado/citologia , Fígado/patologia , Hepatopatias/etiologia , Testes de Função Hepática , Masculino , Pilotos , Veia Porta/fisiopatologia , Ratos , Ratos Wistar
18.
Pak J Pharm Sci ; 32(5(Special)): 2375-2383, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31894021

RESUMO

Rhododendron molle G. Don is an important traditional Chinese medicinal plant, which has been applied to treat some inflammatory diseases. In the present study, ethanol extracts of R. molle flower (RFE) and leaf (RLE) were used for phytochemical, antioxidant and anti-inflammatory analysis. The antioxidant activity was investigated using the free radicals of 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (OH-)-scavenging activity, super oxide anion radical (O2.-)-scavenging activity and iron reducing power (FRAP). Production of nitric oxide (NO) was an indicator to evaluate the anti-inflammatory activity. The results showed that compared with RFE, RLE was more active against DPPH (56.66%), FRAP (51.29%) and hydroxyl radical (OH-) (69.66%) at 100µg/mL. In the same time, RLE and RFE had significant anti-inflammatory activity which could reduce nitrite production from 8.76µM to 5.08µM and 6.01µM, respectively. In addition, GC-MS analysis showed that 43 compounds were identified in R. molle. Among them, 11 compounds had antioxidant and 5 compounds had anti-inflammatory effect. Results showed that ethanol extracts of R. molle have significant antioxidant and anti-inflammatory activity. These results would be helpful for further investigation on the anti-inflammatory mechanism of R. molle.


Assuntos
Antioxidantes/farmacologia , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rhododendron/química , Animais , Antioxidantes/química , Sobrevivência Celular , Radical Hidroxila , Camundongos , Extratos Vegetais/química , Células RAW 264.7
19.
World J Pediatr ; 14(4): 399-403, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29508360

RESUMO

BACKGROUND: To determine whether ex utero intrapartum treatment (EXIT) is an appropriate approach for managing fetuses antenatally diagnosed with giant congenital omphaloceles. METHODS: We retrospectively reviewed patients with omphaloceles who underwent either an EXIT procedure or a traditional repair surgery. Basic and clinical parameters including gender, gestational age, birth weight, maternal blood loss, operative times and operative complications were analyzed. During the 6-12-month follow-ups, postoperative complications including bowel obstruction, abdominal infections, postoperative abdominal distension were monitored, and survival rate was analyzed. RESULTS: A total of seven patients underwent the EXIT procedure and 11 patients underwent the traditional postnatal surgery. We found no differences in maternal age, gestational age at diagnosis, gestational age at delivery and birth weight between the two groups. In the EXIT group, the average operation time for mother was 68.3 ± 17.5 minutes and the average maternal blood loss was 233.0 ± 57.7 mL. The operation time in the EXIT group (22.0 ± 4.5 minutes) was shorter than that in the traditional group (35 ± 8.7 minutes), but the length of hospital stay in the EXIT group (20.5 ± 3.1 days) was longer than that in the traditional group (15.7 ± 2.5 days, P < 0.05). During the follow-up, one patient in the EXIT group had an intestinal obstruction, one developed abdominal compartment syndrome and one died in the traditional group. CONCLUSIONS: In our experience, EXIT is a safe and effective procedure for the treatment of giant congenital omphaloceles. However, more experience is needed before this procedure can be widely recommended.


Assuntos
Doenças Fetais/cirurgia , Hérnia Umbilical/cirurgia , Herniorrafia/métodos , Segurança do Paciente , Resultado da Gravidez , Ultrassonografia Pré-Natal/métodos , Estudos de Coortes , Feminino , Doenças Fetais/diagnóstico por imagem , Seguimentos , Hérnia Umbilical/diagnóstico por imagem , Humanos , Recém-Nascido , Masculino , Gravidez , Cuidado Pré-Natal/métodos , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
20.
J Clin Pathol ; 70(5): 383-389, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27679555

RESUMO

AIM: To evaluate the expression levels and prognostic significance of autophagy-related markers, UNC-51-like kinase1 (ULK1), Beclin1, microtubule-associated protein light chain 3 (LC3), autophagy-related gene 5 (ATG5) and mitochondrion-associated autophagy inhibitor, LRPPRC, in patients with metastatic prostate cancer (PCa) after androgen deprivation therapy (ADT). METHODS: Expressions of ULK1, Beclin1, LC3, ATG5 and LRPPRC were assessed by immunohistochemical examination in 198 patients with metastatic PCa who were receiving ADT (goserelin and bicalutamide). RESULTS: High expression levels of LRPPRC and ULK1were significantly associated with Gleason score, serum prostate-specific antigen (PSA) levels, PSA levels after ADT and number of metastatic sites. High expression of ULK1 in patients with concomitant high expression of LRPPRC was significantly associated with multiple metastases, shorter biochemical progression (BCP)-free survival and shorter overall survival (OS). ULK1 expression, LRPPRC expression, Gleason score, PSA levels after ADT and number of metastatic sites were independently associated with shorter BCP-free survival and OS on multivariate analysis. Furthermore, two-year BCP rate of patients with ≥3 risk factors was found to be significantly higher as compared with that of patients with ≤1 and 2 risk factors. Three-year OS rate in patients with ≥3 risk factors was significantly lower than that of those with ≤1 and 2 risk factors. CONCLUSIONS: High expression of ULK1 concomitant with high expression of LRPPRC may serve as useful markers for shorter BCP-free survival and OS in patients with metastatic PCa after ADT.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Autofagia , Biomarcadores Tumorais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Gradação de Tumores , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia
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