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1.
Heliyon ; 10(11): e32407, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38947441

ABSTRACT

Background: Colchicine is a common therapeutic agent for inflammatory conditions such as gout, yet its narrow therapeutic range frequently results in cases of overdose and subsequent poisoning. Acute colchicine poisoning can be difficult to identify due to its nonspecific clinical manifestations, posing a diagnostic challenge for emergency physicians without a clear history of colchicine ingestion. Case presentation: This report describes a tragic case of acute colchicine poisoning that resulted in three familial homicides. The patients presented with fever, abdominal pain, and diarrhea, which rapidly escalated to shock during their emergency department visits. Laboratory tests revealed a marked leukocytosis, mild elevation in procalcitonin (PCT), significantly elevated creatine kinase (CK) and CK-MB levels, and liver function abnormalities. Despite treatment with carbapenem antibiotics and aggressive fluid resuscitation, the patients' condition deteriorated, marked by a progressive decline in leukocytes and neutrophils. Initially misdiagnosed as septic shock, the ineffectiveness of the standard treatment protocols led to a fatal outcome for all three individuals. Conclusion: Emergency physicians should consider acute colchicine poisoning as a differential diagnosis in patients presenting with shock and the following clinical indicators: (1) pronounced increase in peripheral leukocytes with a disproportionate rise in neutrophils; (2) discordance between the level of serum procalcitonin and the severity of presumed septic shock; (3) early increase in serum creatine kinase (CK) and CK-MB; (4) poor response to antibiotics and resuscitative efforts, accompanied by a continuous decrease in white blood cells and neutrophils. This case underscores the critical need for awareness of colchicine toxicity in the emergency setting, particularly when the clinical presentation mimics septic shock but fails to respond to standard treatments.

2.
J Hazard Mater ; 472: 134493, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38696960

ABSTRACT

Environmental pollution caused by plastic waste has become global problem that needs to be considered urgently. In the pursuit of a circular plastic economy, biodegradation provides an attractive strategy for managing plastic wastes, whereas effective plastic-degrading microbes and enzymes are required. In this study, we report that Blastobotrys sp. G-9 isolated from discarded plastic in landfills is capable of depolymerizing polyurethanes (PU) and poly (butylene adipate-co-terephthalate) (PBAT). Strain G-9 degrades up to 60% of PU foam after 21 days of incubation at 28 â„ƒ by breaking down carbonyl groups via secretory hydrolase as confirmed by structural characterization of plastics and degradation products identification. Within the supernatant of strain G-9, we identify a novel cutinase BaCut1, belonging to the esterase family, that can reproduce the same effect. BaCut1 demonstrates efficient degradation toward commercial polyester plastics PU foam (0.5 mg enzyme/25 mg plastic) and agricultural film PBAT (0.5 mg enzyme/10 mg plastic) with 50% and 18% weight loss at 37 â„ƒ for 48 h, respectively. BaCut1 hydrolyzes PU into adipic acid as a major end-product with 42.9% recovery via ester bond cleavage, and visible biodegradation is also identified from PBAT, which is a beneficial feature for future recycling economy. Molecular docking, along with products distribution, elucidates a special substrate-binding modes of BaCut1 with plastic substrate analogue. BaCut1-mediated polyester plastic degradation offers an alternative approach for managing PU plastic wastes through possible bio-recycling.


Subject(s)
Biodegradation, Environmental , Carboxylic Ester Hydrolases , Polyurethanes , Recycling , Polyurethanes/chemistry , Carboxylic Ester Hydrolases/metabolism , Carboxylic Ester Hydrolases/chemistry , Burkholderiales/enzymology , Burkholderiales/metabolism , Phthalic Acids/metabolism , Phthalic Acids/chemistry , Plastics/chemistry , Plastics/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Polyesters
3.
Nutrition ; 106: 111886, 2023 02.
Article in English | MEDLINE | ID: mdl-36459842

ABSTRACT

OBJECTIVES: Sepsis can cause myocardial injury, which is one of the leading causes of death in critically ill patients. Fish oil rich in omega-3 polyunsaturated fatty acids (PUFAs) in ultralong chains has immunomodulatory effects and can inhibit the production of various critically ill proinflammatory cytokines. Therefore, this study focused on whether ω-3 PUFAs have a protective effect on sepsis-induced cardiomyopathy (SIC). METHODS: Male 6-8 weeks old C57BL/6 mice were pretreated with 3% special fish oil supplement rat food for seven consecutive days prior to surgery. Cecal ligation and puncture (CLP) was perfromed to induce polymicrobial sepsis.The cardiac function was assessed by echocardiography, apoptosis of cardiomyocyte were detected by TUNEL assay and Western blotting, and the level of TNF-α, IL-6, and IL-1ß in plasma was determined 24h after CLP. RESULTS: Pretreatment with omega-3 PUFAs attenuated cardiomyocyte apoptosis, decreased the production of proinflammatory cytokines, attenuated the SIC, and improved the survival rate of septic mice induced by CLP. CONCLUSIONS: ω-3 PUFAs alleviate SIC through attenuating cardiomyocyte apoptosis, which provides a new direction for the prevention and treatment of SIC.


Subject(s)
Apoptosis , Cardiomyopathies , Fatty Acids, Omega-3 , Myocytes, Cardiac , Animals , Male , Mice , Apoptosis/drug effects , Cardiomyopathies/drug therapy , Critical Illness , Cytokines , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Fish Oils/pharmacology , Fish Oils/therapeutic use , Mice, Inbred C57BL , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Sepsis/complications
4.
BMC Emerg Med ; 22(1): 105, 2022 06 11.
Article in English | MEDLINE | ID: mdl-35690727

ABSTRACT

BACKGROUND: With more emergency visits, there is increasing pressure to provide emergency medical services globally and locally. This study aimed to investigate the epidemiological characteristics and the disease spectrum of patients presenting in the last three years to the Department of Emergency Medicine of Tianjin Medical University General Hospital, a tertiary hospital in Tianjin, China, to improve the services of the emergency medicine department. METHODS: A retrospective study was conducted on all patients in the Department of Emergency Medicine of Tianjin Medical University General Hospital from Jan 1, 2017, 00:00:00 to Dec 31, 2020, 23:59:59, including variables like medical record number, gender, age, date of admission, principal diagnosis. The data were analyzed by SPSS statistical software; statistical charts were prepared by GraphPad Prism9.0 and SPSS 20.0; statistical tables were made by Microsoft Excel. RESULTS: A total of 1,314,916 patients presented to the Department of Emergency Medicine of Tianjin Medical University General Hospital from Jan 1, 2017, 00:00:00 to Dec 31, 2020, 23:59:59. In terms of gender distribution, the male-female ratio was 0.78∶1. As for age distribution, patients aged 60-69 were the most (23.47%), and patients younger than 20 years were the least (2.80%). Concerning monthly data, the number of visits peaked during January and December. The distribution of daily visits showed the feature of three highs and a low. The top three prevalence diseases in the emergency disease spectrum were respiratory, cardiovascular, and digestive diseases. The respiratory system was the most common in patients with infectious diseases (200,912, accounting for 86.97%). Among the patients suffering from infectious diseases, the number of patients with respiratory infections peaked in 2019 (73,530) and was the lowest in 2020 (20,078). CONCLUSIONS: From 2017 to 2019, the demand for emergency services in Tianjin Medical University General Hospital continued to increase, but it was greatly affected by COVID-19 in 2020. This emergency department is mainly for patients with respiratory system, circulatory system and digestive system diseases, and its treatment time is relatively centralized. The prevention of diseases for people of all ages, especially female patients and the elderly, should be strengthened, and emergency medical resources should be allocated reasonably according to the peak months and crowed periods of patients.


Subject(s)
COVID-19 , Emergency Service, Hospital , Aged , Female , Hospitals, General , Humans , Male , Retrospective Studies , Tertiary Care Centers
5.
BMC Infect Dis ; 22(1): 564, 2022 Jun 21.
Article in English | MEDLINE | ID: mdl-35729526

ABSTRACT

BACKGROUND: Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis, severe sepsis, and septic shock in China. METHODS: We Searched MEDLINE, Embase, PubMed, and Cochrane Library from 1 January 1992 to 1 June 2020 for studies that reported on the frequency and mortality of sepsis, severe sepsis, and septic shock conducted in China. Random effects models were performed to estimate the pooled frequency and mortality of sepsis, severe sepsis, and septic shock. RESULTS: Our search yielded 846 results, of which 29 studies were included in this review. The pooled frequency of sepsis was estimated at 33.6% (95% CI 25.9% to 41.3%, I2 = 99.2%; p < 0.001), and the pooled mortality of sepsis, severe sepsis and septic shock were 29.0% (95% CI 25.3%-32.8%, I2 = 92.1%; p = 0), 31.1% (95% CI 25.3% to 36.9%, I2 = 85.8%; p < 0.001) and 37.3% (95% CI 28.6%-46.0%, I2 = 93.5%; p < 0.001). There was significant heterogeneity between studies. With a small number of included studies and the changing definition of sepsis, trends in sepsis frequency and mortality were not sufficient for analysis. Epidemiological data on sepsis in the emergency department (ED) are severely lacking, and more research is urgently needed in this area is urgently needed. CONCLUSIONS: Our findings indicated that the frequency and mortality of sepsis and septic shock in China were much higher than North America and Europe countries. Based on our results, an extremely high incidence and mortality of sepsis and septic shock in China's mainland requires more healthcare budget support. Epidemiological data on sepsis and septic shock in ED are severely lacking, and more research is urgently needed in this area. Trial registration This systematic review was conducted according to the statement of the preferred reporting items for systematic review (PROSPERO CRD42021243325) and the meta-analysis protocols (PRISMA-P).


Subject(s)
Sepsis , Shock, Septic , Humans , China/epidemiology , Sepsis/epidemiology , Shock, Septic/epidemiology
6.
Front Physiol ; 13: 834077, 2022.
Article in English | MEDLINE | ID: mdl-35492613

ABSTRACT

Rutin is a flavanol-type polyphenol that consists of flavanol quercetin and the disaccharide rutinose, which has been reported to exert various biological effects such as antioxidant and anti-inflammatory activities. It is not clear whether rutin has a protective effect on sepsis-induced cardiomyopathy (SIC). In this study, we used male C57BL/6 mice and cecal ligation and puncture (CLP) surgery to establish the model of SIC. Rutin was precautionarily treated (50, 100, 200 mg/kg per day, 7 days) before CLP. The results showed that rutin pretreatment (100, 200 mg/kg per day, 7 days) reduced the mortality of murine sepsis. We chose the 100 mg/kg dose for further studies. Mice were pretreatment with rutin (100 mg/kg per day, 7 days) before subjected to CLP, and myocardial tissue and blood samples were collected 24 h after CLP. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cTNT decreased, while interleukin-10 (IL-10) increased with rutin pretreatment. The cardiomyocytes apoptosis and mitochondrial dysfunction were also alleviated with rutin pretreatment. In conclusion, this study confirmed the efficacy of rutin-enriched diet in the prophylaxis of cardiac apoptosis and cardiac injury induced by CLP in mouse model. It provides a potential new approach on SIC prophylaxis in sepsis.

7.
Exp Ther Med ; 22(6): 1396, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34650644

ABSTRACT

In previous studies, miR-132 and miR-223 were considered to be involved in cellular and pathological processes of diseases. However, the role of early diagnosis and prognosis evaluation in sepsis-induced cardiomyopathy (SIC) remains unknown. The present study aimed to explore the diagnostic value of combined detection of miR-132 and miR-223 for SIC and their correlation with creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor α (TNF-α), and interleukin-6 (IL)-6. SIC patients (n=80) admitted to Tianjin Medical University General Hospital were assigned to the research group (RG), while 60 healthy participants receiving physical examinations at the same period were assigned to the control group (CG). Serum expression profiles of miR-132 and miR-223 were detected by the RT-qPCR. CK-MB and cTnI were assessed using chemiluminescence assay, and TNF-α and IL-6 by enzyme-linked immunosorbent assay (ELISA). Serum miR-132 and miR-223 levels were significantly lower in the RG than in the CG (P<0.001). The sensitivity and specificity for the diagnosis of SIC were 82.50 and 71.67% for miR-132, 95.00 and 61.67% for miR-223, as well as 86.25 and 86.67% for miR-132 combined with miR-223. Serum miR-132 and miR-223 levels were significantly higher in the survivor group than in the deceased group (P<0.001). The sensitivity and specificity for the prognosis of SIC were 85.96 and 65.22% for miR-132 combined with miR-223. Serum miR-132 and miR-223 were negatively correlated with serum CK-MB, cTnI, TNF-α, and IL-6 (P<0.001). miR-132 combined with miR-223 can be used for early diagnosis and prognostic evaluation of SIC, and the two are correlated with CK-MB, cTnI, TNF-α, and IL-6.

8.
Resuscitation ; 169: 189-197, 2021 12.
Article in English | MEDLINE | ID: mdl-34624410

ABSTRACT

OBJECTIVE: This study aimed to investigate the predictive value of pulse oximetry plethysmography (POP) for the return of spontaneous circulation (ROSC) in cardiac arrest (CA) patients. METHODS: This was a multicenter, observational, prospective cohort study of patients hospitalized with cardiac arrest at 14 teaching hospitals cross China from December 2013 through November 2014. The study endpoint was ROSC, defined as the restoration of a palpable pulse and an autonomous cardiac rhythm lasting for at least 20 minutes after the completion or cessation of CPR. RESULTS: 150 out-of-hospital cardiac arrest (OHCA) patients and 291 in-hospital cardiac arrest (IHCA) patients were enrolled prospectively. ROSC was achieved in 20 (13.3%) and 64 (22.0%) patients in these cohorts, respectively. In patients with complete end-tidal carbon dioxide (ETCO2) and POP data, patients with ROSC had significantly higher levels of POP area under the curve (AUCp), wave amplitude (Amp) and ETCO2 level during CPR than those without ROSC (all p < 0.05). Pairwise comparison of receiver operating characteristic (ROC) curve analysis indicated no significant difference was observed between ETCO2 and Amp (p = 0.204) or AUCp (p = 0.588) during the first two minutes of resuscitation. CONCLUSION: POP may be a novel and effective method for predicting ROSC during resuscitation, with a prognostic value similar to ETCO2 at early stage.


Subject(s)
Cardiopulmonary Resuscitation , Out-of-Hospital Cardiac Arrest , Carbon Dioxide , Humans , Out-of-Hospital Cardiac Arrest/therapy , Oximetry , Prospective Studies , Return of Spontaneous Circulation
9.
Lupus ; 30(7): 1192-1196, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33784848

ABSTRACT

Acute pericardial tamponade, which can cause obstructive shock, is a serious life-threatening medical emergency that can be readily reversed by timely identification and appropriate intervention. Acute pericardial tamponade can occur for a number of reasons, including idiopathic, malignancy, uremia, iatrogenic, post-myocardial infarction, infection, collagen vascular, hypothyroidism, and others. Systemic lupus erythematosus (SLE) and hyperthyroidism associated with pericardial tamponade are rarely reported. Here, we report the case of a 20-year-old female patient was final diagnosed of SLE with Graves' hyperthyroidism.


Subject(s)
Cardiac Tamponade/etiology , Cardiac Tamponade/surgery , Hyperthyroidism/complications , Lupus Erythematosus, Systemic/complications , Pericardiocentesis/methods , Acute Disease , Antibodies, Antinuclear/immunology , Cardiac Tamponade/diagnosis , Chest Pain/etiology , Cough/etiology , Diagnosis, Differential , Dyspnea/etiology , Echocardiography, Doppler/methods , Female , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/immunology , Treatment Outcome , Young Adult
10.
Intern Emerg Med ; 16(4): 967-973, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33151479

ABSTRACT

Decreased serum thyroid hormone levels and their prediction of mortality in septic patients are still controversial, especially with the evolution of the definition of sepsis. This study aimed to assess the ability of thyroid hormone disorders to predict the early mortality of patients with septic shock defined by Sepsis-3. Sixty-three adult patients with septic shock admitted to a university hospital emergency intensive care unit (EICU) were studied. Serum free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), C-reactive protein (CRP), procalcitonin (PCT), and lactate levels were determined and compared with survival status and organ dysfunction. Among the 63 patients studied, lower serum FT3 and FT4 levels were significantly associated with higher sequential organ failure assessment (SOFA) scores. Patients with septic shock with lower levels of FT3 (≤ 1.70 pmol/L) and FT4 (≤ 9.99 pmol/L) had significantly increased 28-day mortality. There was no significant difference in the serum TSH level between the survivor and nonsurvivor groups. The areas under the receiver operating characteristic curves for FT3 and FT4 levels were associated with 28-day mortality (0.92 and 0.89, respectively) and were higher than that for SOFA (0.82), CRP (0.65) and lactate (0.59). The decrease in serum levels of FT3 and FT4 in patients with septic shock is associated with the severity of organ dysfunction and 28-day mortality. Early detection of serum FT3 and FT4 levels could help clinicians to identify patients at high risk of clinical deterioration.


Subject(s)
Shock, Septic/blood , Shock, Septic/mortality , Thyroid Hormones/blood , China/epidemiology , Female , Humans , Male , Middle Aged , Organ Dysfunction Scores , Predictive Value of Tests , Prospective Studies , Thyroid Function Tests
11.
Cell Death Dis ; 10(10): 782, 2019 10 14.
Article in English | MEDLINE | ID: mdl-31611560

ABSTRACT

Sepsis is a life-threatening organ dysfunction syndrome caused by dysregulated host response to infection that leads to uncontrolled inflammatory response followed by immunosuppression. However, despite the high mortality rate, no specific treatment modality or drugs with high efficacy is available for sepsis to date. Although improved treatment strategies have increased the survival rate during the initial state of excessive inflammatory response, recent trends in sepsis show that mortality occurs at a period of continuous immunosuppressive state in which patients succumb to secondary infections within a few weeks or months due to post-sepsis "immune paralysis." Immune cell alteration induced by uncontrolled apoptosis has been considered a major cause of significant immunosuppression. Particularly, apoptosis of lymphocytes, including innate immune cells and adaptive immune cells, is associated with a higher risk of secondary infections and poor outcomes. Multiple postmortem studies have confirmed that sepsis-induced immune cell apoptosis occurs in all age groups, including neonates, pediatric, and adult patients, and it is considered to be a primary contributing factor to the immunosuppressive pathophysiology of sepsis. Therapeutic perspectives targeting apoptosis through various strategies could improve survival in sepsis. In this review article, we will focus on describing the major apoptosis process of immune cells with respect to physiologic and molecular mechanisms. Further, advances in apoptosis-targeted treatment modalities for sepsis will also be discussed.


Subject(s)
Adaptive Immunity/immunology , Apoptosis/immunology , Inflammation/immunology , Sepsis/immunology , Humans , Immunosuppression Therapy , Inflammation/microbiology , Inflammation/mortality , Inflammation/pathology , Sepsis/microbiology , Sepsis/mortality , Sepsis/pathology
12.
Front Immunol ; 8: 1601, 2017.
Article in English | MEDLINE | ID: mdl-29209331

ABSTRACT

Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a group of cell surface transmembrane receptors expressed on immune cells, and regulate immune balance in inflammatory diseases. Sepsis is a life-threatened inflammatory syndrome induced by infection, and the pathogenesis of sepsis includes immune dysregulation, inflammation, and coagulation disorder. Here, we reviewed the various roles acted by Siglecs family in the pathogenesis of sepsis. Siglec-1, Siglec-5, and Siglec-14 play bidirectional roles through modulation of inflammation and immunity. Siglec-2 regulates the immune balance during infection by modulating B cell and T cell response. Siglec-9 helps endocytosis of toll-like receptor 4, regulates macrophages polarization, and inhibits the function of neutrophils during infection. Siglec-10 inhibits danger-associated molecular patterns induced inflammation, helps the initiation of antigen response by T cells, and decreases B-1a cell population to weaken inflammation. Regulating the Siglecs function in the different stages of sepsis holds great potential in the therapy of sepsis.

13.
Front Immunol ; 8: 1021, 2017.
Article in English | MEDLINE | ID: mdl-28970829

ABSTRACT

Sepsis is a lethal syndrome with a high incidence and a weighty economy burden. The pathophysiology of sepsis includes inflammation, immune dysfunction, and dysfunction of coagulation, while sepsis-induced cardiomyopathy (SIC), defined as a global but reversible dysfunction of both sides of the heart induced by sepsis, plays a significant role in all of the aspects above in the pathogenesis of sepsis. The complex pathogenesis of SIC involves a combination of dysregulation of inflammatory mediators, mitochondrial dysfunction, oxidative stress, disorder of calcium regulation, autonomic nervous system dysregulation, and endothelial dysfunction. The treatments for SIC include the signal pathway intervention, Chinese traditional medicine, and other specific therapy. Here, we reviewed the latest literatures on the mechanisms and treatments of SIC and hope to provide further insights to researchers and create a new road for the therapy of sepsis.

14.
BMC Pulm Med ; 17(1): 127, 2017 Sep 20.
Article in English | MEDLINE | ID: mdl-28931394

ABSTRACT

BACKGROUND: Acute respiratory failure (ARF) is still one of the most severe complications in immunocompromised patients. Our previous systematic review showed noninvasive mechanical ventilation (NIV) reduced mortality, length of hospitalization and ICU stay in AIDS/hematological malignancy patients with relatively less severe ARF, compared to invasive mechanical ventilation (IMV). However, this systematic review was based on 13 observational studies and the quality of evidence was low to moderate. The efficacy of NIV in more severe ARF and in patients with other causes of immunodeficiency is still unclear. We aim to determine the efficacy of the initial ventilation strategy in managing ARF in immunocompromised patients stratified by different disease severity and causes of immunodeficiency, and explore predictors for failure of NIV. METHODS AND ANALYSIS: The VENIM is a multicentre randomized controlled trial (RCT) comparing the effects of NIV compared with IMV in adult immunocompromised patients with severe hypoxemic ARF. Patients who meet the indications for both forms of ventilatory support will be included. Primary outcome will be 30-day all-cause mortality. Secondary outcomes will include in-hospital mortality, length of stay in hospital, improvement of oxygenation, nosocomial infections, seven-day organ failure, adverse events of intervention, et al. Subgroups with different disease severity and causes of immunodeficiency will also be analyzed. DISCUSSION: VENIM is the first randomized controlled trial aiming at assessing the efficacy of initial ventilation strategy in treating moderate and severe acute respiratory failure in immunocompromised patients. The result of this RCT may help doctors with their ventilation decisions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02983851 . Registered 2 September 2016.


Subject(s)
Hypoxia/complications , Noninvasive Ventilation/adverse effects , Respiratory Insufficiency/mortality , Respiratory Insufficiency/therapy , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , China , Double-Blind Method , Female , Hospital Mortality , Humans , Immunocompromised Host , Intubation, Intratracheal , Male , Middle Aged , Noninvasive Ventilation/methods , Organ Dysfunction Scores , Research Design , Young Adult
15.
Mol Med Rep ; 15(3): 1103-1108, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28112366

ABSTRACT

Tumor cells resistant to anoikis are considered to be candidates for metastasis. In the present study, the role of Tim­3 in anoikis and its influence on the invasion of clear cell renal cell carcinoma (ccRCC) was investigated. Here, polyhydroxylethylmethacrylate (poly­HEMA) was applied to two ccRCC cell lines, 786­O and Caki­2, to induce detachment from the extracellular matrix (ECM). Tim­3 mRNA and protein expression levels were assayed by reverse transcription-quantitative polymerase chain reaction (RT­qPCR) and western blot, respectively. Anoikis was measured by Ho33342/PI double staining, acridine orange staining, and further determined using the CytoSelect™ 24­well Anoikis Assay kit. Apoptosis was measured using flow cytometry, E­cadherin and N­cadherin protein expression were determined using western blotting and a Chemicon cell invasion assay kit was used to quantify the invasive capacity of 786­O and Caki­2 cells. It was demonstrated that detachment from the ECM decreases transcription and the protein expression level of Tim­3 in 786­O and Caki­2 cells compared with control cells. Interference with Tim­3 expression using small interfering RNA exacerbated anoikis in 786­O and Caki­2 cells induced by poly­HEMA treatment. E­cadherin upregulation, N­cadherin downregulation, and ECM detachment­induced reduction in invasion ability were all exacerbated by knockdown of Tim­3. In conclusion, interference with Tim­3 expression may attenuate the invasion of renal cell carcinoma by aggravating anoikis, indicating Tim­3 as a potential therapeutic target for treating ccRCC.


Subject(s)
Anoikis/genetics , Carcinoma, Renal Cell/genetics , Hepatitis A Virus Cellular Receptor 2/genetics , Kidney Neoplasms/genetics , RNA Interference , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Survival/genetics , Extracellular Matrix/metabolism , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Hepatitis A Virus Cellular Receptor 2/metabolism , Humans , Kidney Neoplasms/pathology , Neoplasm Invasiveness , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/genetics
16.
Mol Med Rep ; 15(2): 689-695, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28035413

ABSTRACT

T cell immunoglobulin mucin-3 (Tim-3) has previously been implicated in the immune response and tumor biology. Colorectal carcinoma (CRC) is a malignancy, which is closely associated with inflammation. However, the role of Tim­3 in the progression of CRC remains to be fully elucidated. The present study aimed to investigate the role of Tim­3 in the progressive activities of human CRC. A total of 30 clinical CRC tissues and their adjacent tissues were collected. Slides from another 112 cases that underwent CRC surgical resection were also obtained. The protein and mRNA levels of Tim­3 in the clinical tissues and in CRC cell lines were initially examined using western blot and reverse transcription­quantitative polymerase chain reaction analyses, respectively. Immunohistochemical staining was performed to detect Tim­3 in the CRC samples. Specific small interfering (si)RNA against Tim­3 (siTim­3) was synthesized to knock down the expression of Tim­3, and the subsequent effects of Tim­3 knockdown on cell proliferation, migration and invasion were assessed. The data obtained showed that Tim­3 was expressed at high levels in the CRC tissues, compared with the non­cancerous tissues. The expression of Tim­3 in the clinical tissues was significantly associated with tumor size (P=0.007), tumor­node­metastasis staging (P<0.0001) and distant metastasis (P<0.0001). Knockdown of Tim­3 significantly reduced the cell proliferative rate of HCT116 and HT­29 cells. Wound closure activity was also inhibited by knockdown of Tim­3 in these two cell lines, and the migration and invasive abilities of these two cell lines were consistently decreased following knockdown of Tim­3. Taken together, Tim­3 was found to be a critical mediator in the progression of CRC and may serve as a potential therapeutic target for the treatment of CRC.


Subject(s)
Colorectal Neoplasms/pathology , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/metabolism , Up-Regulation , Cell Movement , Cell Proliferation/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/surgery , Female , HCT116 Cells , HT29 Cells , Hepatitis A Virus Cellular Receptor 2/antagonists & inhibitors , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Staging , RNA Interference , RNA, Small Interfering/metabolism , Rectum/metabolism
17.
Oncotarget ; 7(49): 81791-81805, 2016 Dec 06.
Article in English | MEDLINE | ID: mdl-27835904

ABSTRACT

Our previous research showed that neuropilin (Nrp) -1highCD4+CD25+Regulatory T cells (Tregs) exhibited primary negative immunoregulation in sepsis induced immune dysfunction. Tuftsin is the typical ligand of Nrp-1. Herein, we investigated the potential therapeutic value and mechanisms of tuftsin in sepsis. Sepsis per se markedly decreased the serum concentration of tuftsin, administration of tuftsin improved the survival rate of septic mice with cecal ligation and puncture (CLP). In vitro study, tuftsin prevented the negative immunoregulation of Nrp-1highCD4+CD25+Tregs, including weakening the expression of forkhead/winged helix transcription factor (Foxp)- 3/cytotoxic T lymphocyte associated antigen (CTLA)-4, inhibiting the secretion of transforming growth factor (TGF)-ß, and weakening the immunosuppressive function of Nrp-1highCD4+CD25+Tregs to conventional CD4+CD25-T cells. Tuftsin markedly inhibited the demethylation of Foxp3-Tregs specific demethylated region (TSDR) of Nrp-1highCD4+CD25+Tregs. Tuftsin could represent a new potential therapeutic agentia to improve the outcome of septic mice, and associate with preventing the negative immunoregulation of Tregs via Nrp-1.


Subject(s)
Immunologic Factors/pharmacology , Interleukin-2 Receptor alpha Subunit/metabolism , Neuropilin-1/metabolism , Sepsis/drug therapy , T-Lymphocytes, Regulatory/drug effects , Tuftsin/pharmacology , Animals , CTLA-4 Antigen/metabolism , Cells, Cultured , DNA Methylation , Disease Models, Animal , Dose-Response Relationship, Drug , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Interleukin-2 Receptor alpha Subunit/immunology , Male , Mice, Inbred BALB C , Neuropilin-1/immunology , Sepsis/genetics , Sepsis/immunology , Sepsis/metabolism , Signal Transduction/drug effects , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Time Factors , Transforming Growth Factor beta/metabolism
18.
World J Emerg Med ; 4(4): 290-3, 2013.
Article in English | MEDLINE | ID: mdl-25215135

ABSTRACT

BACKGROUND: This study aimed to observe the effect of hemoperfusion (HP) cartridge on different internal environment indicators at different time points in patients with acute blood poisoning and to find alternative indicators for the detection of blood poisoning. METHODS: The levels of internal environment indicators (blood pH, PvCO2, PvO2, blood lactate, potassium, free calcium, bicarbonate, and blood glucose) before and after HP treatment were recorded for patients with acute poisoning at time points of 30 minutes and 120 minutes. After calculating the difference value δ, the statistical software was used to analyze the statistical difference of the influence caused by HP cartridge at two time points. According to the formula, adsorption rate % = ×100, the adsorption rate of each indicator was calculated respectively. RESULTS: The difference of indicators at different time points in inlet and outlet such as blood glucose, free-calcium, and lactate was statistically significant (P<0.05), but the difference in indicators such as pH, PvCO2, PvO2, potassium, sodium, and bicarbonate was not statistically significant (P>0.05). CONCLUSION: During HP treatment, the indicators of blood glucose, free-calcium and lactate were significantly affected by HP cartridge, and the effect varies with time.

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