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1.
Qual Life Res ; 33(1): 207-218, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37824058

ABSTRACT

OBJECTIVE: To investigate the effects of systemic lupus erythematosus (SLE) on health-related quality of life (HRQOL), the relationship between disease activity and HRQOL, and potential factors affecting HRQOL in Chinese SLE patients. METHODS: This study recruited 1568 patients and 2610 controls to explore the effects of SLE on HRQOL. The association between disease activity and HRQOL, and the influencing factors of HRQOL were determined in 1568 patients. Then, we prospectively followed 1096 patients to explore the association between reduced disease activity and improved HRQOL, and the influencing factors of improved HRQOL. The Short-Form 36 (SF-36) and SLE disease activity index (SLEDAI) were used to evaluate HRQOL and disease activity. RESULTS: Chinese SLE patients had lower HRQOL than controls in all domains (P < 0.001), especially in role-physical (RP) and role-emotional (RE). Compared with SLE patients from outside China, the HRQOL of Chinese patients appeared to be higher in mental component summary (MCS) but lower in RP and RE. SLEDAI was negatively correlated with HRQOL, which was validated using the results of a follow-up study, where SLEDAI reduction was positively associated with HRQOL improvements (P < 0.05). Furthermore, personality, life nervous and experiences of adverse life events may influence HRQOL and HRQOL improvements. CONCLUSION: SLE significantly affected the HRQOL of Chinese patients, especially in RP and RE. Disease activity was negatively correlated with HRQOL. We also found for the first time some factors affecting HRQOL, which can be regarded as the basis for improving the HRQOL of SLE patients.


Subject(s)
Lupus Erythematosus, Systemic , Quality of Life , Humans , Quality of Life/psychology , Follow-Up Studies , Severity of Illness Index , Surveys and Questionnaires , Lupus Erythematosus, Systemic/psychology , China
2.
Fa Yi Xue Za Zhi ; 39(3): 231-239, 2023 Jun 25.
Article in English, Chinese | MEDLINE | ID: mdl-37517010

ABSTRACT

Kinship testing is widely needed in forensic science practice. This paper reviews the definitions of common concepts, and summarizes the basic principles, advantages and disadvantages, and application scope of kinship analysis methods, including identity by state (IBS) method, likelihood ratio (LR) method, method of moment (MoM), and identity by descent (IBD) segment method. This paper also discusses the research hotspots of challenging kinship testing, complex kinship testing, forensic genetic genealogy analysis, and non-human biological samples.


Subject(s)
DNA Fingerprinting , Forensic Genetics , Forensic Genetics/methods , Forensic Sciences , Pedigree , Humans
3.
Fa Yi Xue Za Zhi ; 39(3): 240-246, 2023 Jun 25.
Article in English, Chinese | MEDLINE | ID: mdl-37517011

ABSTRACT

Tri-allelic pattern in autosomal STR is a common abnormal typing phenomenon in forensic DNA analysis, which brings difficulties and uncertainties to the evaluation of the evidence weight in actual cases. This paper reviews the types, formation mechanism, occurrence frequency, genetic pattern and quantitative evaluation of evidence of the tri-allelic pattern in autosomal STR in forensic DNA analysis. This paper mainly explains the formation mechanism and genetic patterns based on different types of tri-allelic pattern. This paper also discusses the determination of tri-allelic pattern and the quantitative method of evidence evaluation in paternity testing and individual identification. This paper aims to provide references for scientific and standardized analysis of this abnormal typing phenomenon in forensic DNA analysis.


Subject(s)
Forensic Medicine , Microsatellite Repeats , Alleles , DNA/genetics , Gene Frequency , Humans
4.
Fa Yi Xue Za Zhi ; 39(3): 247-253, 2023 Jun 25.
Article in English, Chinese | MEDLINE | ID: mdl-37517012

ABSTRACT

OBJECTIVES: To study the detection efficiency of trio full sibling with another known full sibling reference added under different number of autosomal STR typing systems. METHODS: Based on 43 detection systems consisting of 13 to 55 representative autosomal STR loci, 10 000 true families (full sibling group) and 10 000 false families (unrelated individual group) were randomly simulated. The full sibling index (FSI) was calculated based on the method of family reconstruction. The cumulative sibling relationship index (CFSI) of 0.000 1 and 10 000 were used as the evaluation thresholds, and the detection efficiency parameters were calculated and compared with the identification of the duo full sibling testing. RESULTS: With the increasing number of STR loci, the error rate and inability of judgement rate gradually decreased; the sensitivity, specificity, correct rate of judgment and other parameters gradually increased, and the system efficiency gradually improved. Under the same detection system, trio full sibling testing showed higher sensitivity, specificity, system efficiency and lower inability of judgement rate compared with duo full sibling testing. When the system efficiency was higher than 0.85 and inability of judgement rate was less than 0.01%, at least 20 STRs should be detected for trio full sibling testing, which was less than 29 STRs required by duo full sibling testing. CONCLUSIONS: The detection efficiency of trio full sibling testing is superior to that of duo full sibling testing with the same detection system, which is an effective identification scheme for laboratories with inadequate detection systems or for materials with limited conditions.


Subject(s)
Microsatellite Repeats , Siblings , Humans , Microsatellite Repeats/genetics , DNA Fingerprinting , Gene Frequency
5.
Fa Yi Xue Za Zhi ; 39(3): 254-261, 2023 Jun 25.
Article in English, Chinese | MEDLINE | ID: mdl-37517013

ABSTRACT

OBJECTIVES: To establish an analytical method for half sibling testing involving common three relatives' participation. METHODS: Based on the half sibling testing scenarios with the known biological mother, grandfather or uncle, and two unidentified controversial half siblings participating, two opposing hypotheses were set. Lineage reconstruction according to Mendel's law of heredity was carried out, and the calculation formula of the half sibling kinship index was derived. Verification of actual cases was carried out and the results were compared with duo half sibling testing. RESULTS: In the scenarios of the known biological mother, grandfather and uncle participating in half sibling testing, the kinship calculation formulae of 54, 91 and 99 genotype combinations for kinship index calculation were deduced respectively. The actual cases showed higher kinship indexes in trio half sibling testing compared with duo half sibling testing. CONCLUSIONS: It is beneficial to obtain more genetic information for family reconstruction and improvement of the strength of genetic evidence for half sibling testing by adding known relatives.


Subject(s)
Mothers , Siblings , Female , Humans , Genotype , Microsatellite Repeats
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(3): 565-573, 2023 May.
Article in Chinese | MEDLINE | ID: mdl-37248585

ABSTRACT

Objective: To explore the protective effect of placenta-derived mesenchymal stem cells (P-MSCs) transplantation on intestinal injury in septic mice and its mechanism. Methods: A total of 24 mice were randomly assigned to 3 groups, a sham operation group, a sepsis group that underwent cecal ligation and puncture (CLP) procedure, and a group that received CLP and P-MSCs treatment. Hereinafter, the three groups are referred to as the Sham group, the CLP group, and the CLP+P-MSCs group. For the mice in the Sham group, the abdomen was cut open and the cecum was exposed and then placed back in the abdomen. CLP was performed in the other two groups to establish the sepsis model. Mice in the Sham and the CLP groups received 0.1 mL of 0.9% NaCl injection in the tail vein 1 hour after operation, while mice in the CLP+P-MSCs group received 2×10 5 P-MSCs infusion 1 hour after operation. Intestinal and blood specimens were collected from the mice in each group 24 hours after P-MSCs transplantation. Hematoxylin and eosin (HE) staining of the intestinal tissue was performed for pathological evaluation. The serum concentrations of D-lactic acid, diamine oxidase (DAO), endotoxin, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-10, and transforming growth factor (TGF)-ß were determined by enzyme linked immunosorbent assay (ELISA). The gene expression of the relevant inflammatory factors in the small intestinal tissue was determined by real-time fluorescence polymerase chain reaction. The expression of zonula occludens protein-1 (ZO-1) and occludin protein in the intestine was determined by Western blot, the infiltration of intestinal macrophages was determined by immunohistochemical method, and the polarization of macrophages was determined by immunofluorescence. Results: The exogenous transplantation of P-MSCs could form colonies in the injured intestines of septic mice. Compared with those of the CLP group, the intestinal injury of the CLP+P-MSCs group was significantly alleviated, the serum concentrations of D-lactic acid, DAO, endotoxin, IL-1ß, IL-6, and TNF-α were significantly decreased ( P<0.05), while the serum concentrations of IL-10 and TGF-ß were significantly increased ( P<0.05), the expression levels of IL-1 ß, TNF-α and IL-6 genes in the intestinal tissue were significantly decreased ( P<0.05), while the expression levels of IL-10 and TGF-ß genes were significantly increased ( P<0.05), and the expression of ZO-1 and occludin proteins in the intestine was also significantly increased ( P<0.05). In addition, the distribution of macrophages in the intestinal tissue of the CLP+P-MSCs group decreased significantly and the macrophages showed a tendency for M2 polarization. Conclusion: Exogenous transplantation of P-MSCs can significantly reduce inflammatory injury and improve the intestinal barrier function in septic mice with intestinal injury. Reduction in the infiltration of macrophages and promotion of the polarization of macrophages from M1 to M2 may be the mechanisms underlying the reduction of inflammation.


Subject(s)
Mesenchymal Stem Cell Transplantation , Sepsis , Mice , Animals , Tumor Necrosis Factor-alpha , Interleukin-10 , Interleukin-6 , Occludin , Transforming Growth Factor beta , Sepsis/therapy , Lactic Acid
7.
Huan Jing Ke Xue ; 44(4): 2356-2364, 2023 Apr 08.
Article in Chinese | MEDLINE | ID: mdl-37040984

ABSTRACT

To investigate the effect of exogenous application of melatonin (MT) on rice seedlings under antimony (Sb) stress, hydroponic experiments were carried out with rice seedlings (Huarun No.2). The fluorescent probe localization technology was used to locate the reactive oxygen species (ROS) in the root tips of rice seedlings, and the root viability, malondialdehyde (MDA) content, ROS (H2O2 and O2-·) content, antioxidant enzyme (SOD, POD, CAT, and APX) activities, and antioxidant (GSH, GSSG, AsA, and DHA) contents in the roots of rice seedlings were analyzed. The results showed that exogenous addition of MT could alleviate the adverse effects of Sb stress on the growth and increase the biomass of rice seedlings. Compared with the Sb treatment, the application of 100 µmol·L-1 MT increased rice root viability and total root length by 44.1% and 34.7% and reduced the content of MDA, H2O2, and O2-· by 30.0%, 32.7%, and 40.5%, respectively. Further, the MT treatment increased the activities of POD and CAT by 54.1% and 21.8%, respectively, and also regulated the AsA-GSH cycle. This research indicated that exogenous application of 100 µmol·L-1MT can promote the growth and antioxidant ability of rice seedlings and alleviate the damage of lipid peroxidation by Sb stress, thus improving the resistance of rice seedlings under Sb stress.


Subject(s)
Melatonin , Oryza , Antioxidants/metabolism , Melatonin/pharmacology , Reactive Oxygen Species , Seedlings , Oryza/metabolism , Antimony , Oxidative Stress , Hydrogen Peroxide/pharmacology
8.
World J Gastroenterol ; 27(43): 7530-7545, 2021 Nov 21.
Article in English | MEDLINE | ID: mdl-34887647

ABSTRACT

BACKGROUND: Severe acute pancreatitis (SAP) is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options. N6-methyladenosine (m6A) modification of circRNAs plays important roles in physiological and pathological processes. However, the roles of m6A circRNA in the pathological process of SAP remains unknown. AIM: To identify transcriptome-wide map of m6A circRNAs and to determine their biological significance and potential mechanisms in SAP. METHODS: The SAP in C57BL/6 mice was induced using 4% sodium taurocholate salt. The transcriptome-wide map of m6A circRNAs was identified by m6A-modified RNA immunoprecipitation sequencing. The biological significance of circRNAs with differentially expressed m6A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The underlying mechanism of m6A circRNAs in SAP was analyzed by constructing of m6A circRNA-microRNA networks. The expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m6A process in SAP. RESULTS: Fifty-seven circRNAs with differentially expressed m6A peaks were identified by m6A-modified RNA immunoprecipitation sequencing, of which 32 were upregulated and 25 downregulated. Functional analysis of these m6A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP, such as regulation of autophagy and protein digestion. In m6A circRNA-miRNA networks, several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m6A circRNAs, such as miR-24-3p, miR-26a, miR-92b, miR-216b, miR-324-5p and miR-762. Notably, the total m6A level of circRNAs was reduced, while the demethylase alkylation repair homolog 5 was upregulated in SAP. CONCLUSION: m6A modification of circRNAs may be involved in the pathogenesis of SAP. Our findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new potential therapeutic targets for SAP.


Subject(s)
MicroRNAs , Pancreatitis , Acute Disease , Adenosine/analogs & derivatives , Animals , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Pancreatitis/chemically induced , Pancreatitis/genetics , RNA, Circular
9.
Yi Chuan ; 43(10): 949-961, 2021 Oct 20.
Article in English | MEDLINE | ID: mdl-34702707

ABSTRACT

Short tandem repeat (STR) markers have been widely used in forensic paternity testing and individual identification, but the STR mutation might impact on the forensic result interpretation. Importantly, the STR mutation rate was underestimated due to ignoring the "hidden" mutation phenomenon in most similar studies. Considering this, we use Slooten and Ricciardi's restricted mutation model based on big data to obtain more accurate mutation rates for each marker. In this paper, the mutations of 20 autosomal STRs loci (D3S1358, D1S1656, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D6S1043, D7S820, D5S818, TPOX, D8S1179, D12S391, D19S433, and FGA; The restricted model does not include the correction factor of D6S1043, this paper calculates remaining 19 STR loci mutation rates) were investigated in 28,313 (Total: 78,739 individuals) confirmed parentage-testing cases in Chinese Han population. As a result, total 1665 mutations were found in all loci, including 1614 one-steps, 34 two-steps, 8 three-steps, and 9 nonintegral mutations. The loci-specific average mutation rates ranged from 0.00007700 (TPOX) to 0.00459050 (FGA) in trio's and 0.00000000 (TPOX) to 0.00344850 (FGA) in duo's. We analyzed the relationship between mutation rates of the apparent and actual, the trio's and duo's, the paternal and maternal, respectively. The results demonstrated that the actual mutation rates are more than the apparent mostly, and the values of µ1"/µ2"(apparent) are also greater than µ1/µ2 (actual) commonly (µ1", µ1; µ2", µ2 are the mutation rates of one-step and two-step). Therefore, the "hidden" mutations are identified. In addition, the mutations rates of trio's and duo's, the paternal and maternal, exhibit significant difference. Next, those mutation data are used to do a comparison with the studies of other Han populations in China, which present the temporal and regional disparities. Due to the large sample size, some rare mutation events, such as monozygotic (MZ) mutation and "fake four-step mutation", are also reported in this study. In conclusion, the estimation values of actual mutations are obtained based on big data, they can not only provide basic data for the Chinese forensic DNA and population genetics databases, but also have important significance for the development of forensic individual identification, paternity testing and genetics research.


Subject(s)
Big Data , Microsatellite Repeats , Gene Frequency , Genetics, Population , Humans , Microsatellite Repeats/genetics , Mutation , Mutation Rate
10.
Yi Chuan ; 43(10): 994-1002, 2021 Oct 20.
Article in English | MEDLINE | ID: mdl-34702712

ABSTRACT

Forensic genetics mainly uses human biological samples as the objects, solves the identification of biological materials related to law by detecting genetic information, provides clues for investigation and evidences for trial, thus facing many ethical issues. This paper put forward the ethical principles in forensic genetics research and practice, and discussed the ethical issues in sample collection, forensic DNA phenotyping, forensic genetic genealogy analysis, forensic DNA database development, paternity and kinship testing, and research data sharing. We suggest that specific ethical requirements should be formulated, the ethical review system should be established for forensic genetics and ethical training for practitioners should be strengthened.


Subject(s)
Databases, Nucleic Acid , Forensic Genetics , DNA , Humans
11.
Food Funct ; 12(12): 5658-5667, 2021 Jun 21.
Article in English | MEDLINE | ID: mdl-34018522

ABSTRACT

Green tea has been considered as a health-promoting beverage and is widely consumed worldwide. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol derived from green tea leaves with potent antioxidative and chemopreventive activities, has been reported to offer protection against inflammation-driven tissue damage. Here, we evaluated the protective effects of EGCG against lung injury during acute pancreatitis (AP) and further revealed the detailed mechanism. The results showed that EGCG significantly attenuated l-arginine-induced AP and the consequent pulmonary damage in mice. Moreover, EGCG substantially attenuated oxidative stress and concurrently suppressed NOD-like receptor protein 3 (NLRP3) inflammasome activation in the lung. In vitro, EGCG considerably reduced the production of mitochondrial reactive oxygen species (mtROS) and oxidized mitochondrial DNA (ox-mtDNA) in alveolar macrophages (AMs) challenged with AP-conditioned plasma. Meanwhile, the amount of ox-mtDNA bound to NLRP3 decreased significantly by the treatment with EGCG, resulting in impaired NLRP3 inflammasome activation. In addition, the antagonism of NLRP3 signaling by EGCG was affected in the presence of the mtROS stimulant rotenone or scavenger Mito-TEMPO. Altogether, EGCG possesses potent activity to attenuate lung injury during AP progression by inhibiting NLRP3 inflammasome activation. As for the mechanism, the EGCG-conferred restriction of NLRP3 inflammasome activation probably arises from the elimination of mtROS as well as its oxidative product ox-mtDNA, which consequently enables the protection against AP-associated lung injury.


Subject(s)
Catechin/analogs & derivatives , Catechin/pharmacology , Inflammasomes/metabolism , Lung Injury/drug therapy , Mitochondria/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pancreatitis/drug therapy , Reactive Oxygen Species/metabolism , Acute Lung Injury/metabolism , Animals , Antioxidants/pharmacology , DNA, Mitochondrial/metabolism , Disease Models, Animal , Inflammasomes/drug effects , Inflammation/metabolism , Lung/pathology , Lung Injury/pathology , Male , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Tea/chemistry
12.
World J Gastroenterol ; 27(9): 815-834, 2021 Mar 07.
Article in English | MEDLINE | ID: mdl-33727772

ABSTRACT

BACKGROUND: Our previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood. AIM: To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms. METHODS: SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 µg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed. RESULTS: APD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury. CONCLUSION: APD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.


Subject(s)
HMGB1 Protein , Pancreatitis , Acute Disease , Animals , Ascites , Drainage , Humans , Inflammation , Male , Pancreatitis/chemically induced , Pancreatitis/therapy , Paracentesis , Rats , Rats, Sprague-Dawley , Signal Transduction , Toll-Like Receptor 4
13.
J Cancer Educ ; 36(3): 603-610, 2021 06.
Article in English | MEDLINE | ID: mdl-31848938

ABSTRACT

To describe the knowledge and attitude of Chinese patients with advanced cancer towards advanced care planning (ACP), a convenience sample of 275 patients with advanced cancer was recruited from a tertiary cancer hospital in Beijing, China, between February and December 2017. The multi-item questionnaire focused on patients' demographics, disease characteristics and knowledge about and attitude towards ACP and was administered to eligible patients. Descriptive statistics were performed. Most patients had never heard about ACP (82.2%) and had never talked about ACP (83.0%), but only a few (18.3%) were not willing to talk about ACP. A total of 67.8% patients chose to refuse resuscitation attempts or life-sustaining medical interventions, and 70.8% of patients hoped to have surrogate decision makers when they became unconscious. By binary logistic regression analysis, patients who were of greater age, female and living in urban areas preferred to refuse resuscitation attempts or life-sustaining medical interventions (OR = 1.023, P = 0.042; OR = 2.011, P = 0.020; OR = 0.254, P < 0.01); patients who had very rich or rich family economic status preferred to involve surrogate decision makers compared with patients of very poor family economic status (OR = 0.250, P = 0.011). There is a large gap between the knowledge about ACP and the expectation of implementing ACP in Chinese patients with advanced cancer. To develop culturally appropriate and individualized programmes to promote knowledge and implementation in practice of ACP among Chinese patients with advanced cancer and their relatives is still a significant challenge.


Subject(s)
Advance Care Planning , Neoplasms , Asian People , China , Female , Humans , Neoplasms/therapy , Surveys and Questionnaires
14.
J Cell Mol Med ; 24(11): 6426-6437, 2020 06.
Article in English | MEDLINE | ID: mdl-32372557

ABSTRACT

We had previously demonstrated that the calcitonin gene-related peptide (CGRP) suppresses the oxidative stress and vascular smooth muscle cell (VSMC) proliferation induced by vascular injury. A recent study also indicated that CGRP protects against the onset and development of angiotensin II (Ang II)-induced hypertension, vascular hypertrophy and oxidative stress. However, the mechanism behind the effects of CGRP on Ang II-induced oxidative stress is unclear. CGRP significantly suppressed the level of reactive oxygen species (ROS) generated by NADPH oxidase in Ang II-induced VSMCs. The Ang II-stimulated activation of both Src and the downstream transcription factor, STAT3, was abrogated by CGRP. However, the antioxidative effect of CGRP was lost following the expression of constitutively activated Src or STAT3. Pre-treatment with H-89 or CGRP8-37 also blocked the CGRP inhibitory effects against Ang II-induced oxidative stress. Additionally, both in vitro and in vivo analyses show that CGRP treatment inhibited Ang II-induced VSMC proliferation and hypertrophy, accompanied by a reduction in ROS generation. Collectively, these results demonstrate that CGRP exhibits its antioxidative effect by blocking the Src/STAT3 signalling pathway that is associated with Ang II-induced VSMC hypertrophy and hyperplasia.


Subject(s)
Angiotensin II/pharmacology , Calcitonin Gene-Related Peptide/metabolism , NADPH Oxidases/metabolism , Reactive Oxygen Species/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/physiology , src-Family Kinases/metabolism , Animals , Antioxidants/metabolism , Calcitonin/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Oxidative Stress/physiology , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects
15.
World J Gastroenterol ; 26(1): 35-54, 2020 Jan 07.
Article in English | MEDLINE | ID: mdl-31933513

ABSTRACT

BACKGROUND: Abdominal paracentesis drainage (APD) is a safe and effective strategy for severe acute pancreatitis (SAP) patients. However, the effects of APD treatment on SAP-associated cardiac injury remain unknown. AIM: To investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms. METHODS: SAP was induced by 5% sodium taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after SAP induction. Morphological staining, serum amylase and inflammatory mediators, serum and ascites high mobility group box (HMGB) 1, cardiac-related enzymes indexes and cardiac function, oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats. Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined. RESULTS: APD treatment improved cardiac morphological changes, inhibited cardiac dysfunction, decreased cardiac enzymes and reduced cardiomyocyte apoptosis, proapoptotic Bax and cleaved caspase-3 protein levels. APD significantly decreased serum levels of HMGB1, inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury. Furthermore, the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis. CONCLUSION: APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress, which may be a novel mechanism behind the effectiveness of APD on SAP.


Subject(s)
Heart Injuries/physiopathology , Heart Injuries/therapy , Oxidative Stress/physiology , Pancreatitis/therapy , Paracentesis/methods , Abdomen , Acute Disease , Animals , Disease Models, Animal , Heart Injuries/etiology , Myocardium , Pancreatitis/chemically induced , Pancreatitis/complications , Rats , Rats, Sprague-Dawley , Taurocholic Acid
16.
Biochim Biophys Acta Mol Basis Dis ; 1866(5): 165685, 2020 05 01.
Article in English | MEDLINE | ID: mdl-31953217

ABSTRACT

Progression of acute pancreatitis (AP) into a severe form usually results in a life-threatening condition with multiple organ dysfunction, and in particular acute lung injury (ALI), often contributes to the majority of AP-associated deaths. Increasing evidence has shown that uncontrolled activation of the immune system with rapid production of inflammatory cytokines play a dominant role in this process. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome, is recently reported to be involved in the pathogenesis of AP progression, however, the relationship between NLRP3 inflammasome activation and AP-associated lung injury remains unclear yet. Here, we show that NLRP3 inflammasome activation and subsequent pyroptosis in alveolar macrophages (AMs) is responsible for the lung injury secondary to AP. In addition, plasma-derived exosomes from AP mice is capable of triggering NLRP3-dependent pyroptosis in AMs. Inhibition of exosome release or uptake in vivo by inhibitors substantially suppresses AMs pyroptosis and thereby alleviates AP-induced pulmonary lesion. Collectively, the current work reveals for the first time the involvement of NLRP3-dependent pyroptosis induced by plasma exosomes in the pathogenesis of AP-induced ALI, suggesting that the exosome-mediated NLRP3 inflammatory pathway is a potential therapeutic target for the treatment of lung injury during AP.


Subject(s)
Acute Lung Injury/immunology , Exosomes/metabolism , Inflammasomes/immunology , Macrophages, Alveolar/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pancreatitis/complications , Acute Lung Injury/blood , Acute Lung Injury/pathology , Animals , Arginine/administration & dosage , Arginine/toxicity , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Disease Models, Animal , Exosomes/immunology , Humans , Macrophages, Alveolar/immunology , Male , Mice , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Pancreatitis/blood , Pancreatitis/chemically induced , Pancreatitis/immunology , Pyroptosis/immunology
17.
Biochem Biophys Res Commun ; 521(2): 285-289, 2020 01 08.
Article in English | MEDLINE | ID: mdl-31668374

ABSTRACT

Apoptosis is associated with various cardiovascular diseases. CGRP exerts a variety of effects within the cardiovascular system, and protects against the onset and development of angiotensin (Ang) II-induced vascular dysfunction and remodelling. However, it is not known whether CGRP has a direct effect on Ang II-induced apoptosis in vascular smooth muscle cells (VSMCs), and the mechanism underlying the anti-apoptotic role remains unclear. In this study, CGRP significantly suppressed reactive oxygen species (ROS) and apoptosis in Ang II-induced VSMCs. In VSMCs pre-treated with a CGRP receptor antagonist (CGRP8-37), the CGRP-mediated inhibition of Ang II-induced ROS and apoptosis was completely abolished. Moreover, pre-treatment with N-acetyl-L cysteine (NAC), an ROS scavenger, blocked the effects of CGRP on Ang II-induced apoptosis. In addition, the activation of CaMKII and the downstream transcription factor CREB stimulated by Ang II was abrogated by CGRP. Importantly, in both CGRP and NAC-treated VSMCs, CGRP failed to further attenuate CaMKII and CREB activation. The results demonstrate that CGRP attenuated Ang II-induced ROS-dependent apoptosis in VSMCs by inhibiting the CaMKII/CREB signalling pathway.


Subject(s)
Angiotensin II/pharmacology , Apoptosis , Calcitonin Gene-Related Peptide/physiology , Muscle, Smooth, Vascular/cytology , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Cells, Cultured , Cyclic AMP Response Element-Binding Protein/metabolism , Humans
18.
Sensors (Basel) ; 19(8)2019 Apr 15.
Article in English | MEDLINE | ID: mdl-30991688

ABSTRACT

The present study uses a method to address microvibrations effects on an optical satellite by combining simulations and experiments based on high-precision acceleration sensors. The displacement and angular displacement of each optical component can be obtained by introducing flywheel perturbation data from a six-component test bench to the finite element model of the optical satellite. Combined with an optical amplification factor inferred from the linear optical model, the pixel offset of the whole optical system is calculated. A high accuracy and broad frequency range for a new microvibration measurement experimental system is established to validate the simulation. The pixel offset of the whole optical system can be measured by testing the acceleration signals of each optical component and calculating optical amplification factors. The results are consistent with optical imaging test results, indicating correctness of the experimental scheme and the effectiveness of the simulation. The results suggest that the effect of microvibrations on a camera can be verified by using mechanical simulators instead of a whole optical camera for the experiment scheme, which is demonstrated to be an effective way for increasing efficiency in jitter measurements.

19.
World J Gastroenterol ; 24(45): 5131-5143, 2018 Dec 07.
Article in English | MEDLINE | ID: mdl-30568390

ABSTRACT

AIM: To investigate the role of peritoneal macrophage (PM) polarization in the therapeutic effect of abdominal paracentesis drainage (APD) on severe acute pancreatitis (SAP). METHODS: SAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot. RESULTS: APD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin (IL)-1ß, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of pro-inflammatory mediators, such as IL-1ß and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP model rats. CONCLUSION: These findings suggest that APD treatment exerts anti-inflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanism underlying its therapeutic effect.


Subject(s)
Macrophages, Peritoneal/immunology , Pancreatitis/therapy , Paracentesis , Peritoneal Cavity/cytology , Animals , Biomarkers/analysis , Disease Models, Animal , Humans , Macrophages, Peritoneal/metabolism , Male , Pancreatitis/chemically induced , Pancreatitis/diagnosis , Pancreatitis/immunology , Rats , Rats, Sprague-Dawley , Severity of Illness Index , Taurocholic Acid/toxicity , Treatment Outcome
20.
Ann Hum Biol ; 45(4): 359-364, 2018 Jun.
Article in English | MEDLINE | ID: mdl-30200780

ABSTRACT

AIM: To evaluate the 23 autosomal short tandem repeat (STR) loci included in GoldenEye™ 25 A kit using forensic human identification and paternity testing. SUBJECTS AND METHODS: In total, 3751 unrelated individuals from the Southern Chinese Han population were genotyped with the 5-dye GoldenEye™ 25 A multiplex amplification system. PCR products were separated using arrayed capillary electrophoresis. Allele frequencies and forensic parameters for the 23 autosomal STR loci were statistically analysed. RESULTS: A total of 344 alleles were observed, with corresponding allelic frequencies ranging from 0.0001-0.5519 for the 23 STR loci. No significant deviation from the Hardy-Weinberg equilibrium and linkage disequilibrium was observed. The combined power of discrimination (CPD) was 1-1.6290 × 10-28 and the combined power of exclusion (CPE) was 0.999 999 999 89 and 0.999 999 286 93 for trio and duo cases, respectively. From 3865 meioses, 87 mutation events were discovered. The mutation rate varied from 0-0.00285 for each locus. One-step mutation accounted for 94.25% of total mutations. The ratio of paternal vs maternal mutation was 3.76:1.13 kinds of n/(n + 1) heterozygote genotypes were observed. CONCLUSIONS: The results show that 23 STR loci of GoldenEye™ 25 A kit are highly polymorphic in the Southern Chinese Han population, indicating the kit is suitable for forensic application.


Subject(s)
Gene Frequency , Microsatellite Repeats/genetics , Mutation , Polymorphism, Genetic , China , Humans
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