Nuclear factor-erythroid 2 related factor 2 (Nrf2) is an ubiquitous and important transcription factor. It regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. A large body of research showed that Nrf2-Keap1 (Kelch-like ECH-associated protein 1, Keap 1)-ARE signaling pathway is involved in the endogenous antioxidant defense mechanisms. Nrf2 increases the expression of a number of cytoprotective genes, protects cells and tissues from the injury of a variety of toxicants and carcinogens. As a result, Nrf2 enhances the expression of glutathione and antioxidants such as superoxide dismutase and glutathione S-transferase, and subsequently scavenging free radicals. Air pollution especially from PM2.5 particles, is associated with an increasing morbidity of inflammatory pulmonary diseases and their deterioration. More and more studies demonstrated that Nrf2 was a novel signaling molecule in the modulation of inflammatory responses in these inflammatory respiratory diseases, such as asthma, acute lung injury (ALI) and COPD. Therefore, Nrf2 targeting might be a therapeutic target, which will provide clinical benefit by reducing both oxidative stress and inflammation in asthma, acute lung injury (ALI) and COPD. This review focused on the relationship between Nrf2 and inflammatory respiratory diseases and oxidative stress.
Acute Lung Injury ; metabolism ; pathology ; Antioxidants ; metabolism ; Glutathione ; Glutathione Transferase ; metabolism ; Humans ; Inflammation ; metabolism ; pathology ; Lung ; pathology ; NF-E2-Related Factor 2 ; metabolism ; Oxidative Stress ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology ; Signal Transduction

Objective : To investigate the incidence of suspected adverse events following immunization(AEFI) in Chongchuan District, Nantong City, Jiangsu Province from 2008 to 2022, so as to provide insights into safety assessment of vaccines. Methods: The data on AEFI surveillance in Chongchuan District from 2008 to 2022 were collected through the National Immunization Program Information Management System of China, including demographics, history of vaccination, laboratory tests, incidence of AEFI and clinical characteristics. The epidemiological, clinical characteristics and reported incidence of AEFI were analyzed in Chongchuan District from 2008 to 2022 using a descriptive epidemiological method. Results: The reported incidence of AEFI in Chongchuan District from 2008 to 2022 appeared a tendency towards a decline (P<0.05), and the annual average reported incidence was 50.85/105. The incidence of AEFI associated with vaccines included in the national immunization program was significantly higher than that caused by vaccines that were not included in the national immunization program (74.67/105 vs. 20.35/105, P<0.05). General reaction was the predominant type of AEFI (1 937 cases, 44.21/105), and there were 274 cases with abnormal reactions (6.25/105) and 17 cases with coincident syndromes (0.39/105); however, no vaccine quality or vaccination accidents occurred. A high incidence rate was seen in AEFI associated with vaccines administered by subcutaneous (75.05/105) and intramuscular injection (47.40/105), and a low incidence rate was found in AEFI associated with vaccines administered orally (16.41/105). The five highest reported incidence rates of AEFI were found for the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b vaccine (312.01/105), 7-valent pneumococcal polysaccharide-protein conjugate vaccine (292.14/105), inactivated Japanese encephalitis vaccine (248.37/105), Group ACYW135 meningococcal polysaccharide vaccine (240.67/105) and combined live vaccine for measles and rubella (229.31/105). The general reactions mainly included fever, redness and swelling and induration (1 878 cases, 96.95%), and abnormal reactions mainly included allergic skin rash (241 cases, 87.96%). In addition, 91.34% of AEFI occurred within 24 hours after vaccination, and 99.73% of cases with AEFI were cured during the 3-month follow-up. Conclusions The reported incidence of AEFI appeared a tendency towards a decline in Chongchuan District from 2008 to 2022. General reaction was the predominant type of AEFI, and all AEFI showed a good prognosis. The safety of vaccines was high in Chongchuan District from 2008 to 2022.

China ; History, 20th Century ; History, 21st Century ; Pathology ; Periodicals as Topic ; history

Fourteen compounds were isolated from the n-butanol fraction of the 95% aqueous ethanol extract of the stems and twigs of Strychnos cathayensis by D101 macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography, and semipreparative RP-HPLC. Their structures were elucidated as ethyl 4-O-β-D-allopyranosyl-vanillate (1), n-butyl 4-O-β-D-allopyranosyl-vanillate (2), n-butyl 4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillate (3), n-butyl 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillate (4), n-butyl 4-O-(6′-O-syringoyl)-β-D-glucopyranosyl-vanillate (5), n-butyl 4-O-α-L-rhamnopyranosyl-syringate (6), methyl 3-methoxy-4-(β-D-allopyranosyloxy) benzoate (7), pseudolaroside B (8), butyl syringate (9), glucosyringic acid (10), methyl syringate (11), methyl 4-hydroxy-3-methoxybenzoate (12), clemochinenoside C (13), and clemoarmanoside A (14), respectively, on the basis of spectroscopic data interpretation and by comparison with literature information. Compounds 1-6 are artificial products of phenolic acid esterified by ethanol or n-butanol. It is noted that the precursors (4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillic acid and 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillic acid) of compounds 3 and 4 are new compounds. The hepatoprotective, anti-inflammatory, antioxidant and cytotoxic activities of compounds 1-13 were evaluated in vitro at a concentration of 10 μmol·L^-1. Compounds 1, 2 and 6-10 exhibited potential hepatic protection effects with cell survival rates ranging from 53.6% to 55.5% (acetaminophen, 45.4% at 8 mmol·L^-1). Compound 4 demonstrated anti-inflammatory activity with nitric oxide inhibitory rate of 74.6%. Compounds 3 and 5 showed potential antioxidant activities with malondialdehyde inhibitory rates of 53.2% and 56.1%, respectively.

OBJECTIVETo gain an insight into the relations between human leukocyte antigen-DRB1 (HLA-DRB1) alleles and idiopathic thrombocytopenic purpura (ITP) in children.

METHODSPolymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) was used to identify DRB1 alleles of 42 children with ITP. Among them, 36 were identified for anti-GPIIb/IIIa and anti-GPIb/Ix autoantibody by modified monoclonal antibody specific immobilization of platelet antigens.

RESULTSCompared with health controls, the frequency of HLA-DRB1*17 significantly increased (P<0.05, relative risk=2.76, etiologic factor=0.1064) and the frequency of HLA-DRB1*1202 significantly decreased (P<0.025, relative risk=0.20, prophylactic factor=0.7616) in children with ITP. In comparison with patients of good response to steroids and IVIgG therapy, the frequency of HLA DRB1*11 significantly increased (Chi-square=6.091, P<0.025) in patients with a poor response, furthermore, the most of HLA-DRB1*11 positive patients were female teen-agers. Twenty-seven patients (75%) had anti GPIIb/IIIa and seventeen (47.22%) had anti_GPIb/Ix autoantibodies. The positivities of both anti_GP IIb/IIIa (P=0.02) and anti-GPIb/Ix (P=0.01) were associated with HLA-D RB1*02. However, the positivity of autoantibodies between refractory and non-refractory patients showed no significant difference.

CONCLUSIONThe allele of HLA-DRB1*17 seems to predict susceptibility of ITP in children, while HLA-DRB1*1202 appears to be protective to ITP. The allele of HLA DRB1*11 plays an important role in resistance to steroid and IgG therapy in children with ITP. It seems that the response to the antigenic epitope of GPIIb/IIIa and GPIb/Ix is restricted by HLA-DRB1*02, while the presence of the antibodies could not predict prognosis. In conclusion, the above preliminary findings indicate that genetic factors influence the clinical course of ITP, but the exact mechanism needs to be investigated further.

Adolescent ; Alleles ; Autoantibodies ; blood ; Child ; Child, Preschool ; DNA ; genetics ; Drug Resistance ; genetics ; Female ; Gene Frequency ; Genotype ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Humans ; Immunoglobulin G ; therapeutic use ; Male ; Platelet Glycoprotein GPIIb-IIIa Complex ; immunology ; Platelet Glycoprotein GPIb-IX Complex ; immunology ; Platelet Membrane Glycoproteins ; Purpura, Thrombocytopenic, Idiopathic ; blood ; drug therapy ; genetics ; Steroids ; therapeutic use

To clarify the thrombopoietin (TPO) production in patients with end-stage liver cirrhosis and uremia under hemodialysis, plasma TPO levels in patients with liver cirrhosis (n = 15), uremia under hemodialysis (n = 20) and healthy controls (n = 40) were measured by using a sandwich enzyme linked immunosorbent assay. Relationship between megakaryocytopoiesis and plasma TPO levels was analysed by linear regression. The results showed that the mean plasma TPO concentration in the uremic patients was significantly lower than that in the healthy volunteers, whereas plasma TPO level in end-stage liver cirrhosis was not significantly different from that of normal controls; plasma TPO levels in liver cirrhosis and uremic patients did not significantly influence megakaryocytopoiesis. It is concluded that end-stage liver cirrhosis patients maintained normal plasma TPO levels, but the production of TPO was significantly reduced in renal failure patients. Thrombocytopenia in liver cirrhosis appears to be not related to plasma TPO levels.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Liver Cirrhosis ; blood ; Male ; Middle Aged ; Thrombopoiesis ; Thrombopoietin ; blood ; Uremia ; blood

Objective:To investigate the features of volume, distribution, grading and staging of prostate cancer(PCa)examined via whole-mount histopathology in transitional PCa.Methods:A total of 129 PCa patients undergone radical prostatectomy(RP)between July 2017 and March 2020 whose whole-mount prostate specimens were prepared after surgery were retrospectively studied.Pathological data on tumor locations, diameters and classification of the International Society of Urologic Pathology(ISUP), radiological data on regions of interest(ROI)and scores of the Prostate Imaging and Reporting Data System(PI-RADS v2)were recorded.The results of pathological whole-mount sections and prostate imaging were compared, and the characteristics and detection rates of lesions in different prostate regions were analyzed.Results:Of all 129 prostate specimens from RP, a total of 213 PCa lesions were detected through whole-mount histopathology.There were 21(9.9%)lesions involving both the peripheral zone(PZ)and the transition zone(TZ), with an average diameter of(2.82±0.71)cm.Of all lesions, 85(39.9%)involved PZ and 107(50.2%)involved TZ, with an average diameter of(1.36±0.81)cm and of(1.60±0.94)cm, respectively.The percentage of lesions involving TZ was higher than that lesions involving PZ, with larger diameters( P<0.05). Of 64 patients with complete MRI data, 105 PCa lesions were detected histopathologically by using whole mount sections, while 75 PCa lesions were detected by MRI, with a statistical difference( P<0.05). For lesions≥1.0 cm or lesions with an ISUP grade group≥2, the detection rate of MRI was lower in TZ lesions( P<0.05). Conclusions:PCa lesions within TZ account for a large proportion and have a relatively large tumor dimeter.PCa lesions within TZ are more likely to be missed in clinical examinations and on MRI, and clinicians should pay close attention during diagnosis and treatment.

Objective To construct phage display single-chain antibody fragments (scFvs) library against histidine-rich protein Ⅱ (HRP-Ⅱ) of Plasmodium falciparum and select specific scFvs of anti- HRP-Ⅱ for the purpose of malaria diagnosis. Method The genes of variable fragments of heavy chain (VH) and light chain (VL) were gained from the spleen cells of BALB/c mice immunized with HRP-Ⅱ protein. The VH and VL genes were then assembled by the method of splicing overlapping extension and cloned into phagemid vector pCANTAB 5E. The scFv phage antibodies were expressed at the surface of the phage after the rescue by helper phage M13K07. HRP- Ⅱ protein was used as antigenic reagent for panning and screening. Results The total RNA from the spleen cells was isolated, and cDNA obtained and VH and VL gene regions amplified using PCR. The VH and VL gene regions were combined with a flexible linker ligated into the pCANTAB 5E phagemid vector, and transformed into TG1 Escherichia coli. The repertoire of the phage antibody was about 106. After panning and screening, 8 positive clones expressed scFv antibodies which were specific for HPR-Ⅱ as demonstrated by ELISA. Conclusion Phage display technology can be used as a powerful tool in making scFv antibodies which have the potential to be used as reagents in the diagnosis and therapy of malaria.

Objective To construct phage display single-chain antibody fragments (scFvs) library against histidine-rich protein Ⅱ (HRP-Ⅱ) of Plasmodium falciparum and select specific scFvs of anti- HRP-Ⅱ for the purpose of malaria diagnosis. Method The genes of variable fragments of heavy chain (VH) and light chain (VL) were gained from the spleen cells of BALB/c mice immunized with HRP-Ⅱ protein. The VH and VL genes were then assembled by the method of splicing overlapping extension and cloned into phagemid vector pCANTAB 5E. The scFv phage antibodies were expressed at the surface of the phage after the rescue by helper phage M13K07. HRP- Ⅱ protein was used as antigenic reagent for panning and screening. Results The total RNA from the spleen cells was isolated, and cDNA obtained and VH and VL gene regions amplified using PCR. The VH and VL gene regions were combined with a flexible linker ligated into the pCANTAB 5E phagemid vector, and transformed into TG1 Escherichia coli. The repertoire of the phage antibody was about 106. After panning and screening, 8 positive clones expressed scFv antibodies which were specific for HPR-Ⅱ as demonstrated by ELISA. Conclusion Phage display technology can be used as a powerful tool in making scFv antibodies which have the potential to be used as reagents in the diagnosis and therapy of malaria.

AIM:To investigate the mechanism of quercetin improving rat coronary artery myogenic response under high glucose ( HG) by measuring muscle tension of coronary arterial ring and recording voltage -gated K +channel ( Kv) current of coronary artery smooth muscle cells by whole cell patch clamp .METHODS:The coronary rings from the normal SD rats were acutely isolated , and then divided into 6 groups:(1) control group;(2) HG group;(3) HG+low dose (3 μmol/L) of quercetin group;(4) HG+moderate dose (10 μmol/L) of quercetin group; (5) HG+high dose (30 μmol/L) of quercetin group;(6) HG+C6303 (PKC inhibitor) +high dose of quercetin group.Determinations of coronary artery response to vasoconstrictor (60 mmol/L KCl or 0.1 mmol/L U46619) or vasodilator (Ach at 10 -9 ~10 -5 mol/L) were performed, and the percentage of coronary ring tension was calculated using the contraction as 100%caused by 60 mmol/L KCl.The rat coronary artery smooth muscle cells were acutely isolated for recording the Kv current using whole cell patch clamp .RESULTS:Compared with control group , the contraction amplitudes to 60 mmol/L KCl or 0.1 mmol/L U46619 were significantly increased under HG incubation .Quercetin intervention concentration-dependently re-duced the coronary artery contraction amplitude .Incubation of PKC specific inhibitor C 6303 attenuated the effect of querce-tin.Compared with control group , the diastolic amplitude to Ach decreased significantly in HG group , and quercetin inter-vention concentration-dependently increased the coronary artery diastolic amplitude .Incubation of PKC specific inhibitor C6303 attenuated the effect of quercetin .Compared with control group , HG incubation inhibited Kv current of coronary ar-tery vascular smooth muscle cells significantly , and quercetin intervention attenuated the inhibitory effect of HG on Kv cur-rent intensity .Incubation of PKC specific inhibitor C 6303 attenuated the effect of quercetin .CONCLUSION: Quercetin has a protective effect on myogenic response of coronary artery under HG and the effects is related to the increase in Kv cur -rent and the activation of PKC in vascular smooth muscle cells .