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High-mobility group box 1 (HMGB1) is a non-histone nuclear protein in most eukaryocytes. Inside the nucleus, HMGB1 plays an important role in several DNA events such as DNA repair, transcription, telomere maintenance, and genome stability. While outside the nucleus, it fulfils more complicated functions, including promoting cell proliferation, inflammation, angiogenesis, immune tolerance and immune escape, which may play a pro-tumoral role.Meanwhile, HMGB1 acts as an anti-tumoral protein by regulating immune cell recruitment and inducing immunogenic cell death (ICD) during the carcinogenesis process. Therefore, abnormal expression of HMGB1 is associated with oncogenesis, development, and metastasis of cancer, which may play a dual role of pro-tumor and anti-tumor.
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Humans , Carcinogenesis , Cell Proliferation , HMGB1 Protein/metabolism , Neoplasms/pathology , Neovascularization, PathologicABSTRACT
Objective: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tract tumors with a poor prognosis and high recurrence rate. Recently, ferroptosis resistance has been found in PDAC. However, the underlying mechanism of ferroptosis resistance has not been fully elucidated. Cytochrome P4502J2 (CYP2J2) is the main enzyme which mediates arachidonic acid to produce epoxyeicosatrienoic acids (EETs) in human tissues. It has been reported that EETs involve in the development of cancer, while the roles of EETs in PDAC and ferroptosis remain unclear. This study aims to explore the effect of CYP2J2/EETs on ferroptosis of human pancreatic ductal adenocarcinoma cells PANC-1 cells and the underlying mechanisms.Methods: The tumor tissues and para-carcinoma tissues of 9 patients with PDAC were collected and the expression of CYP2J2 was detected with real-time PCR and Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET), and the degradation product of 8,9-epoxyeicosa-trienoic acid (8, 9-EET). PANC-1 cells were used in this study. The ferroptosis inducer erastin was used to induce ferroptosis. The intracellular long-chain acyl-CoA synthetase 4 (ACSL4) protein level, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) content, Fe2+concentration, and cell survival were detected. The 8, 9-EET was pretreated to observe its effect on erastin-induced ferroptosis in PANC-1 cells. Lentivirus was used to construct a CYP2J2 knockdown cell line to observe its effect on the ferroptosis of PANC-1 cells induced by erastin. A peroxisome proliferation-activated receptor γ (PPARγ) blocker was used to observe the effect of 8, 9-EET on erastin-induced glutathione peroxidase 4 (GPX4) and MDA content in PANC-1 cells.Results: High expression of CYP2J2 was found in PDAC, accompanied by an increased level of 8, 9-DHET. The 8, 9-EET pretreatment significantly attenuated the PANC-1 cell death induced by erastin. The 8, 9-EET reduced the Fe2+ concentration, LDH activity and MDA content, and ACSL4 protein expression in erastin-treated PANC-1 cells. The 8,9-EET also restored the ferroportin (FPN) and ferroptosis suppressor protein 1 (FSP1) mRNA expressions in erastin-treated PANC-1 cells. But CYP2J2 knockdown exacerbated the erastin-induced ferroptosis in PANC-1 cells. Besides, CYP2J2 knockdown furtherly down-regulated the gene expression of FPN and FSP1. The 8, 9-EET increased the expression of GPX4 in the erastin-treated PANC-1 cells, which was eliminated by a PPARγ blocker GW9662. And GW9662 abolished the anti-ferroptosis effects of 8,9-EET. Conclusion: CYP2J2/EETs are highly expressed in PDAC tissues. EETs inhibit the ferroptosis via up-regulation of GPX4 in a PPARγ-dependent manner, which contributes to the ferroptosis resistance of PDAC.
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With advanced brewing technology and contemporary table culture， alcohol drinking， which can be traced back to Dukang wine in the Xia dynasty， is very common in China. However， excessive alcohol intake can easily cause alcohol liver damage， ranging from abdominal pain and venous thrombosis to severe hypoglycemia and fat embolism， coma shock and even life-threatening cases. Puerariae Lobatae Radix has a cool property and sweet taste， with functions of antipyretic， promoting the secretion of saliva or body fluid， rash and hangover alleviation， and so on. It was first recorded in Shen Nong's Materia Medica and has been listed as a special anti-alcoholic medicine in traditional Chinese medicine since ancient times. For example， the ancient medical book Compendium of Materia Medica and other records claim that Puerariae Lobatae Radix has the effect of relieving alcohol and protecting the liver. At the same time， Puerariae Lobatae Radix has a long history in both medicine and food. It was listed in the List of Articles That Both Serve as Food and Medicine published by the National Health Commission. Therefore， there are many products containing pueraria for hangover and liver protection. Prior to this， many scholars have carried out relevant researches on the anti-alcoholism efficacy of Puerariae Lobatae Radix， but there is a lack of systematic summaries. The author has consulted relevant domestic and foreign literatures in recent years. The related products were summarized and it was found that the anti-alcoholic effect of pueraria root mainly came from puerarin， pueraria flavonoids and pueraria polysaccharide， puerarin polypeptide， pueraria daidzein and its derivatives， including the main mechanisms such as inhibiting alcohol absorption， accelerating metabolism， anti-oxidation， protection of liver and cardiomyocytes， and neuroprotection. Related products are abundant and well evaluated， but research on related genes needs to be deepened. This article reviews the main anti-alcoholic components， mechanism of action and related products of pueraria， and puts forward suggestions for future research directions， hoping to provide reference for further related research.
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There are 486 kinds of health food with Puerariae Lobatae Radix as the main raw material, mainly including health food for protecting liver, health food for regulating blood lipid, health food for adjusting blood pressure, health food for regulating blood sugar, and health food for regulating immunity.Based on the establishment of a health food recipe database with Puerariae Lobatae Radix as the main raw material, the Apriori algorithm in association rules was used to explore the formula rule of health food of Puerariae Lobatae Radix.The results showed that among the 174 kinds of hepatoprotective health food, the most used raw materials were Noveniae Fructus and Schisandrae Chinensis Fructus;the common combinations of three raw materials were Puerariae Lobatae Radix-Gardeniae Fructus-Paeoniae Radix Alba, Puerariae Lobatae Radix-Gynostemmatis Pentaphylli Herba-Cassiae Semen, etc.Among the 91 kinds of health food for regulating blood lipid, the most widely used raw materials were Cassiae Semen and Gynostemmatis Pentaphylli Herba;the common combinations of three raw materials were Puerariae Lobatae Radix-Cassiae Semen-Chrysanthemi Flos, Puerariae Lobatae Radix-Alismatis Rhizoma-Mori Folium, etc.Among the 41 kinds of health food for regulating blood pressure, the most widely used raw materials were Eucommiae Cortex and Salviae Miltiorrhizae Radix et Rhizoma;the common combinations of the three raw materials were Puerariae Lobatae Radix-Cassiae Semen-Ostreae Concha, Puerariae Lobatae Radix-Salviae Miltiorrhizae Radix et Rhizoma-Sophorae Flos, etc.Among the 105 kinds of health food for regulating blood sugar, the most widely used raw materials were Dioscoreae Rhizoma and Astragali Radix;the common combinations of three raw materials were Puerariae Lobatae Radix-Notoginseng Radix et Rhizoma-Lycii Cortex, Puerariae Lobatae Radix-Dioscoreae Rhizoma-Poria, Puerariae Lobatae Radix-Dioscoreae Rhizoma-Lycii Cortex, etc.Among the 75 kinds of health food for regulating immunity, the most widely used raw materials were Astragali Radix and Lycii Fructus;the common combinations of three raw materials were Puerariae Lobatae Radix-Gastrodiae Rhizoma-Eucommiae Cortex, Puerariae Lobatae Radix-Mori Fructus-Lonicerae Japonicae Flos, Puerariae Lobatae Radix-Panacis Quinquefolii Radix-Crataegi Fructus, etc.
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Objective@#To explore the effect of hematopoietic cytokines IL-11 on invasion and metastasis abilities of anaplastic thyroid cacinoma(ATC) cells.@*Methods@#Real-time PCR was performed for examining the IL-11 mRNA expression in thyroid carcinoma cell lines, and IL-11 protein expression in the supernament of thyroid carcinoma cell lines was detected by ELISA. Molecular cloning was employed to construct IL-11 stable knockdown cell line; MTT assay was used to analyze the effect of IL-11 on the proliferation of ATC cells; Transwell and wound healing assays were employed to analyze the abilities of migration and invasion in ATC cells. Western blotting was used to detect the relative pathway proteins. SPSS statistical package 19.0 was used to analyze the date, and Student′s t test was used for multiple comparisons.@*Results@#The protein level of IL-11 were significantly lower in knock-down cell lines than that in negative control cell lines(21.55±1.69, 16.18±0.85, 26.37±2.00 vs 54.54±3.99, all P<0.05). Colony formation assays reveal that colony number between knock-down cells and negative control cells has no significance(P>0.05). Meanwhile, MTT assays show that there is no significance between knock-down cell lines and negative control cell line(P>0.05). However, Transwell invasion and migration assays show that number of migrated cells is increased when ATC cells were treated with rhIL-11(0-100 ng/ml)at increasing concentrations.@*Conclusion@#IL-11 improves the migratory and invasive abilities of ATC cells via inducing EMT of ATC cells, and it can be used as a potential target for ATC molecular targeted therapy.
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Objective Comprehensive geriatric assessment is the core technology,this paper describes the concept of comprehensive geriatric assessment,objects,content,assessment methods,interventions and research pro-gress,provide experience to carry out comprehensive geriatric assessment in Tibet,the Tibet region to explore for com-prehensive geriatric assessment mode.
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To analyze the differentially expressed proteins which interacted with NF-kappaB in the uterine lower segment smooth muscle tissues under different status of labor onset, and to provide a new foundation on the mechanisms for labor onset. Methods: NF-κB P65 protein expression in smooth muscle tissues from the term non-labor group, natural term labor group and drug-induced term labor group was analyzed by Western blot. Co-immunoprecipitation and SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) were performed to detect the proteins interacting with NF-κB p65 in the NF-κB p65 complexes. The components of the complex were identified by LC-ESI-MS/MS (liquid chromatography-tandem electrospray mass spectrometry) and database analysis. The identified differentially expressed proteins were confirmed by Western blot. Results: Positive expression of NF-κB was detected in all of the three groups. 10 differentially expressed proteins were identified by LC-ESI-MS/MS in human lower segment myometrium tissues in the term non-labor group and natural term labor group, mean while, 5 differentially expressed proteins were identified in the term non-labor group and the drug-induced labor group. 3 differential expression proteins were detected in all of the 3 groups, including Heat shock 70, Annexin A6 and Desmin, which were verified by Western blot. These proteins were mainly involved in chaperone, signal transduction, cell structure, and energy metabolism process, respectively. Conclusion: NF-κB expressed in uterine smooth muscle cells is involved in the process of initiation and regulation of labor onset through a number of proteins relevant to signal transduction, cell structure and energy metabolism.
Subject(s)
Female , Humans , Pregnancy , Blotting, Western , Electrophoresis, Polyacrylamide Gel , Energy Metabolism , Genetics , Immunoprecipitation , Labor, Obstetric , Genetics , Molecular Chaperones , Genetics , Myocytes, Smooth Muscle , Myometrium , Physiology , NF-kappa B , Genetics , Physiology , Protein Interaction Mapping , Proteomics , Signal Transduction , Genetics , Tandem Mass Spectrometry , Transcription Factor RelAABSTRACT
Objective:To investigate the diagnosis and treatment significance of invasive and noninvasive operation for ventilator?as?sociated pneumonia ( VAP ) . Methods:A total of 80 cases of VAP suspected patients who had received mechanical ventilation at least 48 hours in ICU from Jun 2014 to Mar 2015 were enrolled. Patients were randomly divided into four groups including noninvasive operation group ( F) , invasive operation group ( Q) , mix group 1 ( H1) and mix group 2 ( H2) . VAP diagnosis rate between groups as well as living time, antibiotic use time, survival rate, calcitonin levels and APACHE II score, oxygenation index were analyzed. Results:Specimen from invasive operation had higher specimens to cultivate positive rate than that from noninvasive operation ( P<0?05), but there was no statistic significant difference in VAP diagnosis rate between two methods (P>0?05). Conclusion:Noninva?sive operation collecting samples for VAP diagnosis is also accurate as invasive one. Collecting specimens from sputum suction tube in the clinical treatment on airway suction is a low cost and simple noninvasive operation.
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Patients with advanced gastric cancer lose the surgical indications.Chemotherapy can improve the overall survival and quality of life,which is the main treatment option.But there is no standard chemotherapy regimen for the patients with advanced gastric cancer.Since its initial approval,S-1 is widely used in gastric cancer.Several studies were performed to explore combinations of S-1 with other cytotoxic drugs such as platinum,docetaxel,paclitaxel,and irinotecan.All these combinations were found to be promising,with response rates of around 40％-50％ and relatively favorable safety profiles.
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<p><b>OBJECTIVE</b>To investigate the treatment and prognosis of the patients with oral mucosal melanoma (OMM).</p><p><b>METHODS</b>The clinicopathological and follow-up data of patients with OMM in Sun Yat-sen University Cancer Center from January 1976 to December 2005 were analyzed retrospectively.</p><p><b>RESULTS</b>Fifty-one cases were analyzed. The pathological lymph node metastasis rate was 61% (31/51) and the affected sites were confined to level I(b)-III (94%). The overall three year and five yearsurvival rates were 35% and 21% respectively. No significant difference of three year and five year survival rates were found between the group of incisional biopsy and the group of excisional biopsy. The prognosis was not affected by pigmentation. The survival rate of the patients receiving surgery combined with biotherapy or biochemotherapy was significantly higher than that of the patients treated by other modalities (P = 0.003).</p><p><b>CONCLUSIONS</b>In patients with OMM, lymph node metastasis was mostly confined to level I(b)-III. Incisional biopsy and pigmentation were not associated with an unfavorable prognosis. The prognosis of the patients with OMM was poor and the patients may get a better prognosis by receiving surgery combined with biotherapy or biochemotherapy.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , BCG Vaccine , Therapeutic Uses , Combined Modality Therapy , Follow-Up Studies , Interferon-gamma , Therapeutic Uses , Interleukin-2 , Therapeutic Uses , Lung Neoplasms , Lymph Node Excision , Lymphatic Metastasis , Melanoma , Drug Therapy , Pathology , General Surgery , Melanoma-Specific Antigens , Metabolism , Mouth Mucosa , Pathology , General Surgery , Mouth Neoplasms , Drug Therapy , Pathology , General Surgery , Retrospective Studies , S100 Proteins , Metabolism , Survival RateABSTRACT
OBJECTIVE To evaluate the clinic feature and therapeutic principles and to improve curative effect of mucoepidemoid carcinoma originated in nasal cavity and nasal sinuses. METHODS A restrospective review of clinic features ,therapeutic methods and consequences was undertaken in thirty cases with nasal cavity and nasal sinuse mucoepidemoid carcinoma and treated at the 81st hospital of CPLA from 1990 to 2001. RESULTS Twenty patients received surgery、radiotherapy and chemotherapy, of which sixteen survived in five to ten years follow-up . Six patients received surgery and radiotherapy, of which four survived in five years follow-up. Only one out of two patients who received radiotherapy and chemotherapy respectively survived in five years follow-up. The total five years survival rate was 73 %(22/30). CONCLUSION CT or MRI scan may be helpful to evaluate the location and scale of mucoepidemoid carcinoma.Final diagnosis rely on histopathology examination. Early radical resection combined with radiotherapy and chemotherapy pre- or postoperatively could improve five-year-survival rate and reduce recurrence rate.
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Objective To explore the classification of contrecoup orbital wall fractures, the mechanism of their formation and their identification in forensic practice. Method Forty-Two eases of contrecoup orbital wall fraeture were reviewed and studied. Each case has clear history of injury and both eyes have been clinically checked and CT scan performed. Results The contrecoup orbital wall fracture amounts up to 6.2% among eye socket wall fractures. Forty-two cases with home lateral injuries showed eyeball blunt contusion, 18 of them had retina concussion, 15 eyes had diplopia, no fracture on the orbital walls of that side were found by CT scanner. The 42 eyes on the opposite side of the injuries did not show eyeball contusion or retina concussion, but 10 eyes had diplopia and the orbital internal wall fractures were found in all cased by CT scanner. All 84 eyes of these eases had decreased of blurring of vision. Conclusion The main criteria for diagnosing contrecoup orbital wail, fracture is the found of head trauma with home lateral eyeball blant injury and orbital wall fracture at the opposite side proven by CT scanner and also some degree of injury in the eyeball on that side. The damage was assessed to be of minor injury.