Effects of deltamethrin on the activation or expression of Nrf2 and on the GCS-HS protein level in primary astrocytes with laser scanning confocal microscope

Objective： To examine the effects of deltamethrin（DM） and tBHQ on the activation of Nrt2 and expression of GCS-HS in primary astrocytes. Methods： Rat primary astrocytes were treated with DM （10μmol/L） and tBHQ （40μmol/L）, for 1 and 6 h respectively. Results： Analysis using immunofluorescent confocal microscopy revealed that tBHQ treatment led to a dramatic increase in the level of Nrt2. The ratio of cytoplasmic Nrt2 protein to nuclear Nrt2 protein was markedly reduced in astrocytes by either tBHQ or DM treatment. The level of Nrf2 was reduced by combined tBHQ with DM treatment for 1 h, but treatment the ratio of cytoplasmic Nrf2 protein to nuclear Nrf2 protein was increased compared with that of the tBHQ only. The expression of GCS-HS in astrocytes was not altered by DM or tBHQ or both in astrocytes. Conclusion： These findings demonstrated for the first time that Nrf2 was activated by pesticides and antioxidants in astrocytes, implicating a tote of Nrf2 in response to pesticide neurotoxicity ingla.

Protective effect of LIF-huM SCs on the retina of diabetic model rats

AIM:To investigate the protective effect of human umbilical cord mesenchymal stem cells(hUCMSCs)modified by the LIF gene on the retinal function of diabetic model rats and preliminarily explore the possible mechanism.METHODS:A stably transfected cell line of hUCMSCs overexpressing leukemia inhibitory factor(LIF)was constructed.Overexpression was verified by fluorescent quantitative polymerase chain reaction(qPCR).Forty-eight adult Sprague-Dawley rats were randomly divided into a normal control group(group A),streptozotocin-induced diabetic control group(group B),diabetic rats at 3mo injected with empty vector-transfected hUCMSCs(group C)or injected with LIF-hUCMSCs(group D).Four weeks after the intravitreal injection,analyses in all groups included retinal function using flash electroretinogram(F-ERG),retinal blood vessel examination of retinal flat mounts perfused with fluorescein isothiocyanate-dextran(FITCdextran),and retinal structure examination of sections using hematoxylin and eosin staining.Expression levels of adiponectin(APN),high-sensitivity C-reactive protein(hsCRP),and neurotrophin-4(NT-4)in each group was detected using immunohistochemistry,PCR,Western blotting,and ELISA,respectively.RESULTS:A stable transgenic cell line of LIF-hUCMSCs was constructed.F-ERG and FITC-dextran examinations revealed no abnormalities of retinal structure and function in group A,severe damage of the retinal blood vessels and function in group B,and improved retinal structure and function in group C and especially group D.qPCR,ELISA,and Western blot analyses revealed progressively higher APN and NT-4 expression levels in groups B,C,and D than in group A.hs-CRP expression was significantly higher in group B than in groups A,C,and D,and was significantly higher in group C than in group D(P<0.05).CONCLUSION:LIF-hUCMSCs protect the retina of diabetic rats by upregulating APN and NT-4 expression and downregulating hs-CRP expression in the retina.

Immunotherapy with activation of NK cells

Given the role of CAR-T cell in the fight against cancer cells,as well as the role of NK cell as an innate immune cell with anti-tumor function too,we hypothesize that Insert the CD16 antibody-producing gene or activator protein CD16,CD16 is one of the most important markers of NK cell activation for ADCC,into the CAR-T cell panel.So with this hypothesis in addition to the role of CAR-T cells to fight cancer,the role of NK cells in the fight against cancer too.

Potential new metabolic approach for treatment of diabetes mellitus: converting glucose to ascorbic acid (vitamin C)

Through changing in lifestyle and increasing the global prevalence of diabetes mellitus, its crucial to find new approaches for treatment of this disease. This metabolic disease is characterized by hyperglycemia, insulin de ficiency or insulin resistance. This disorder categorized into type 1 and type 2 diabetes. Type 1 usually initiate from childhood, have an autoimmune background and associated with destroying of beta cells of pancreas. Type 2 diabetes is defined as insulin resistance, hyperglycemia and usually appears in adulthood. In the process of diabetes, hyperglycemia and oxidative stress can induce diabetic retinopathy, nephropathy, neuropathy and cardiovascular disease. According to literature, oxidative stress and chronic inflammation play an essential role in initiation and development of the complications of diabetes. Hence, inhibition of chronic inflammation and oxidative stress besides with glycemic control is important to prevent from these clinical complications. Some researches explained the antioxidant and anti- inflammatory property of vitamin C in patients with diabetes mellitus. Moreover, ascorbic acid can help to better glycemic control in these patients. Thus, we propose a new idea to convert excess amount of glucose to vitamin C for treatment of patients with diabetes mellitus. By performing this idea, we can achieve to better clinical management of diabetes in terms of glycemic control and prevention of oxidative stress which lead to significant decrease in clinical complications.

Hypopharyngeal cancer trends in a high-incidence region:A retrospective tertiary single center study

BACKGROUND Hypopharyngeal cancer has the bleakest prognosis among head and neck cancers due to its extensive submucosal involvement,advanced tumor stage,and limited surgical reconstruction options.Its primary causes include alcohol consumption,tobacco use,genetic predisposition,1`diet,and socioeconomic conditions.While squamous cell carcinoma(SCC)accounts for 95%of hypopharyngeal tumors,it remains a rare form,comprising only 3%-5%of all SCC cases in the head and neck region.Globally,Central and Eastern Europe have the highest incidence rates for males(3.9 per 100000)and the third highest for females(2.26 per 100000),underscoring the significance of this seemingly uncommon condition.In Romania,hypopharyngeal cancer ranked 24th in incidence rate,with 634 new cases in 2020.AIM To study the incidence,treatment and survival rates of hypopharyngeal tumor cases in a major ear,nose,throat(ENT)surgical center.METHODS A retrospective epidemiological clinical study was conducted on patients diagnosed and treated for hypopharyngeal cancer at the ENT department of"Carol Davila Central University Emergency Military Hospital"in Bucharest between January 2018 and August 2022.The study included 53 patients and was authorized by the Ethics Committee of Titu Maiorescu Doctoral School(Bucharest,Romania)and the Ethics Committee of Carol Davila Central University Emergency Military Hospital(Bucharest,Romania).Inclusion criteria required a positive histopathological diagnosis of hypopharyngeal cancer,tumor localization in the hypopharyngeal region,and informed consent for data usage.Exclusion criteria involved major psychiatric pathologies and disagreement for data usage.Diagnosis was based on ENT assessment,imaging reports,and laboratory data.Treatment methods were determined based on various factors.Additional tools,such as Adult Comorbidity Evaluation-27 and Karnofski Performance Status Scale,were used for risk assessment and functional capacity evaluation.Quality of life aspects were measured using the European Organisation for Reasearch and Treatment of Cancer Quality of Life Questionnaire Head and Neck-35 questionnaire.RESULTS Our retrospective study examined 53 patients with hypopharyngeal cancer between January 2018 and August 2022.The majority of patients were male(94.3%),with an average age at diagnosis of 62.5 years.Among the patients,20.75%were employed,66.03%were retired,and 9.43%were unemployed.Smoking was prevalent among 69.81%of patients,while alcohol consumption was frequent in 32.07%of cases.The tumors were mostly diagnosed at an advanced stage(stage IV)and were predominantly SCC.Comorbidities were present in 83.01%of patients,with cardiovascular diseases being the most common.Dysphagia and neck mass were the most common symptoms reported.Treatment methods included surgery,radiation therapy,and chemotherapy.A favorable treatment response was observed in 22.64%of cases,while relapse occurred in 6 cases.Follow-up data was unavailable for some patients.CONCLUSION In summary,our findings align with existing literature;however,we observed a higher severity.

Comparable efficacy of 100 mg aspirin twice daily and rivaroxaban for venous thromboembolism prophylaxis following primary total hip arthroplasty:a randomized controlled trial

Background:Aspirin has demonstrated safety and efficacy for venous thromboembolism(VTE)prophylaxis following total hip arthroplasty(THA);however,inconsistent dose regimens have been reported in the literature.This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA.Methods:Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin(100 mg twice daily)or rivaroxaban(10 mg once daily).Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence,deep vein thrombosis(DVT)on Doppler ultrasonography,total blood loss(TBL),laboratory bloodwork,Harris hip score(HHS),post-operative recovery,and the incidence of other complications.Results:We included 70 patients in this study;34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis,respectively.No cases of symptomatic VTE occurred in this study.The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group(8.8%vs.8.3%,χ^(2)=0.01,P=0.91),confirming the non-inferiority of aspirin for DVT prophylaxis(χ^(2)=2.29,P=0.01).The calculated TBL in the aspirin group(944.9 mL[658.5-1137.8 mL])was similar to that in the rivaroxaban group(978.3 mL[747.4-1740.6mL])(χ^(2)=1.55,P=0.12).However,there were no significant inter-group differences in HHS at post-operative day(POD)30(Aspirin:81.0[78.8-83.0],Rivaroxaban:81.0[79.3-83.0],χ^(2)=0.43,P=0.67)and POD 90(Aspirin:90.0[89.0-92.0],Rivaroxaban:91.5[88.3-92.8],χ^(2)=0.77,P=0.44),the incidence of bleeding events(2.9%vs.8.3%,χ^(2)=0.96,P=0.33),or gastrointestinal complications(2.9%vs.5.6%,χ^(2)=1.13,P=0.29).Conclusion:In terms of safety and efficacy,the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA.This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs.Trial Registration:Chictr.org,ChiCTR18000202894;http://www.chictr.org.cn/showproj.aspx?proj=33284.