Effects of Se-enriched yeast on the amelioration of atrazine-induced meat quality degradation.

Atrazine (ATR) is herbicide that causes serious harm to the environment and threatens human food safety. Se-enriched yeast is the best organic selenium source for protecting cells from damage caused by poisonous substances. To explore mechanism of ATR on meat quality degradation and potential protective effects of Se-enriched yeast on ATR-induced muscle injury, quails were treated with ATR and/or Se-enriched yeast for 28 days. The results found ATR disrupted muscle fiber structure and decreased pH, tenderness, water-holding capacity, essential amino acid content and polyunsaturated fatty acid content. ATR aggravated oxidative stress and inflammation by inhibiting Nrf2 pathway and activating NF-κB pathway, ultimately causing apoptosis. However, Se-enriched yeast alleviated ATR-induced alterations in muscle chemical and physical properties by inhibiting oxidative stress and inflammation. Taken together, these results revealed that ATR exposure caused meat quality degradation and Se-enriched yeast had the potential to counteract ATR-induced myotoxicity by inhibiting oxidative stress and inflammation.

The major histocompatibility complex participates in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the substantia nigra and the aggregation of alpha-synuclein (α-syn). The central nervous system (CNS) has previously been considered as an immune-privileged area. However, studies have shown that the immune responses are involved in PD. The major histocompatibility complex (MHC) presents antigens from antigen-presenting cells (APCs) to T lymphocytes, immune responses will be induced. MHCs are expressed in microglia, astrocytes, and dopaminergic neurons. Single nucleotide polymorphisms in MHC are related to the risk of PD. The aggregated α-syn triggers the expression of MHCs by activating glia cells. CD4+ and CD8+ T lymphocytes responses and microglia activation are detected in brains of PD patients. In addiction immune responses further increase blood-brain barrier (BBB) permeability and T cell infiltration in PD. Thus, MHCs are involved in PD through participating in immune and inflammatory responses.

Ameliorative effect and mechanism of curcumin on diabetes model rats with depression / 中国药房

OBJECTIVE To study the ameliorative effect and potential mechanism of curcumin on diabetes model rats with depression based on cAMP response element binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathway. METHODS The diabetes model rat with depression was established by high fat and high sugar diet+intraperitoneal injection of streptozotocin+chronic unpredictable stress-induced depression. The successfully modeled rats were randomly divided into model group， positive control group （0.18 g/kg metformin and 1.8 mg/kg fluoxetine， gavage）， curcumin low-dose and high-dose groups （30， 60 mg/kg， gavage） and curcumin high-dose+CREB inhibitor group [60 mg/kg curcumin （gavage）+5 mg/kg CREB inhibitor 666-15 （intraperitoneal injection）]， with 12 rats in each group. Another 12 healthy rats were selected as the normal group. Each group was given a corresponding intervention for 4 weeks， the fasting blood glucose level of rats was detected， and the depression of rats was assessed. The levels of corticosterone （CORT） and inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin- 1β （IL-1β）， IL-6] in serum， and the levels of norepinephrine （NE） and 5-hydroxytryptamine （5-HT） in hippocampal tissue were determined. The pathological changes and neuronal apoptosis were observed in the hippocampal tissue of rats in each group； the expression levels of CREB， BDNF mRNA and protein in hippocampal tissue were detected. RESULTS Compared with the normal group， the hippocampal tissue of rats in the model group was severely damaged， and neurons were scattered， while the fasting blood glucose， the forced swimming immobility time， the tail suspension immobility time， serum levels of CORT， TNF-α， IL-1β and IL-6， and neuron apoptosis indexes were all increased or prolonged significantly （P＜0.05）. The levels of NE and 5-HT， the number of surviving neurons， and the expression levels of CREB and BDNF mRNA and protein in hippocampal tissue were decreased significantly （P＜0.05）. Compared with the 的model group， the damage to hippocampal tissue was relieved in the positive control group and curcumin groups， while the above indexes were improved significantly （P＜0.05）. The improvement effect of curcumin high-dose group was better than that of curcumin low-dose group （P＜0.05）. CREB inhibitor could significantly reverse the ameliorative effect of high-dose curcumin on the model rats （P＜0.05）. CONCLUSIONS Curcumin can improve the depression of diabetes model rats with depression， and relieve neuronal damage and inflammatory response， the mechanism of which may be associated with activating CREB/BDNF signaling pathway.

Chitosan Oligosaccharides Alleviate Heat-Stress-Induced Lipid Metabolism Disorders by Suppressing the Oxidative Stress and Inflammatory Response in the Liver of Broilers.

Heat stress has been reported to induce hepatic oxidative stress and alter lipid metabolism and fat deposition in broilers. Chitosan oligosaccharides (COSs), a natural oligosaccharide, has anti-oxidant, anti-inflammatory, and lipid-lowering effects. This study is conducted to evaluate dietary COS supplementation on hepatic anti-oxidant capacity, inflammatory response, and lipid metabolism in heat-stressed broilers. The results indicate that heat-stress-induced poor (p < 0.05) growth performance and higher (p < 0.05) abdominal adiposity are alleviated by COS supplementation. Heat stress increases (p < 0.05) serum AST and ATL activity, serum and liver MDA, TG, TC, and LDL-C levels, and the expression of hepatic IL-1ß, IL-6, SREBP-1c, ACC, and FAS, while it decreases (p < 0.05) serum SOD and CAT activity, liver GSH-Px and SOD activity, and the expression of hepatic Nrf2, GPX1, IL-10, MTTP, PPARα, and CPT1. Nevertheless, COS supplementation decreases (p < 0.05) serum AST and ATL activity, serum and liver MDA, TG, TC, and LDL-C levels, and the expression of hepatic IL-1ß, IL-6, SREBP-1c, ACC, and FAS, while it increases (p < 0.05) serum SOD and CAT activity, liver GSH-Px activity, and the expression of hepatic Nrf2, CAT, IL-10, LPL, MTTP, PPARα, and CPT1. In conclusion, COS could alleviate heat-stress-induced lipid metabolism disorders by enhancing hepatic anti-oxidant and anti-inflammatory capacity.

[Effect of heat-reinforcing needling on expression of P2X7R, NLRP3 and Caspase-1 in synovial tissues of knee joint in rabbits with cold syndrome rheumatoid arthritis].

OBJECTIVE: To observe the effects of heat-reinforcing needling on the expression of purinergic ligand-gated ion channel 7 receptor(P2X7R)，Nodlike receptor protein 3(NLRP3) and Caspase-1 in synovium tissues of knee joint of rabbits with cold syndrome rheumatoid arthritis(RA)，so as to explore the anti-inflammatory mechanism of heat reinforcing needling in the treatment of RA. METHODS: Thirty male New Zealand white rabbits were randomly divided into normal group, model group, reinforcing-reducing needling group(RRG), heat-reinforcing needling group(HRG), and antagonist group(AG), with 6 rabbits in each group.The model of cold syndrome RA was established by ovalbumin combined with Freund's adjuvant and cryogenic freezing. Rabbits of RRG and HRG were treated with corresponding acupuncture techniques on both sides of "Zusanli"(ST36) for 30 min, once a day for 7 days; Rabbits of the AG was intraperitoneally injected with A438079(2.5 mg/kg), once a day for 7 days. After intervention, color Doppler ultrasound was used to observe the joint cavity effusion, synovial thickness and internal blood flow signal.The histomorphological changes of synovial tissues were observed by HE staining. Quantitative real-time PCR method was used to detect the mRNA expression levels of P2X7R, NLRP3, and Caspase-1 in synovial tissues. Western blot was used to detect the protein expression of interleukin(IL)-1ß, IL-6 and tumor necrosis factor(TNF)-α in synovial tissues. RESULTS: Compared with the normal group, the synovial tissues in the model group was thickened, linear and punctate blood flow signals were increased, joint effusion was obvious, synovial coating cells were enlarged, the synovial matrix was severely hyperplasia, inflammatory cells infiltration was obvious.The mRNAs expression levels of P2X7R, NLRP3, Caspase-1 and IL-1ß, IL-6, TNF-α proteins in synovial tissues were significantly increased(P<0.01). Compared with model group, abnormal blood flow signals, synovial thickness, joint effusion, proliferation of synovial matrix, inflammatory cell infiltration and synovial coating cells in the RRG, HRG and AG were improved. The mRNAs expression levels of P2X7R, NLRP3, Caspase-1 and IL-1ß, IL-6, TNF-α proteins in synovial tissues were decreased in the RRG, HRG and AG (P<0.05, P<0.01). Compared with the RRG, the above indexes were lower in the HRG and AG (P<0.05, P<0.01).There was no significant difference in all indexes above between the HRG and AG (P<0.01, P<0.05). CONCLUSION: Heat reinforcing needling can improve synovial inflammation of RA, which may be related to regulating the expressions of P2X7R/NLRP3/Caspase-1 signaling pathway.

The impact of medical insurance reimbursement on postoperative inflammation reaction in distinct cardiac surgery from a single center.

BACKGROUND: Evidences shows that socioeconomic status is reversely associated with the risk of morbidity and mortality for people with cardiovascular disease via pro-inflammation mechanism, but the population profile is not deeply defined on. We aimed to investigate the impact of medical insurance coverage on postoperative systemic inflammatory reaction in two kinds of disease populations undergoing distinct cardiac procedures. METHODS: A total of 515 patients receiving open mitral valve procedure with high-total expense from May 2013 through May 2021 in Sichuan Provincial People's Hospital were retrospectively collected and stratified according to medical insurance reimbursement: low coverage with high out-pocket (< 30%), medium coverage (≤ 60%, but ≥ 30%), and high coverage (> 60%). Another 118 cases undergoing atrium septum defect (ASD) or patent foramen ovale (PFO) occlusion and taking on consistent low-total expense and low-coverage (< 30%) were also classified according to their insured conditions. The postoperative systemic inflammatory response indexes were high sensitivity C-reactive protein (hs-CRP) and the neutrophil-lymphocyte ratio (NLR). RESULTS: Low insurance reimbursement population undergoing open mitral valve procedure had a higher level of hs-CRP and NLR but not troponin I protein or lactate within 48 h postoperatively, and higher thoracic drainage, longer ventilation use and stay in intensive care unit. No significant difference in inflammatory indexes existed among diverse medical insurance coverage in population undergoing ASD/PFO occlusion. CONCLUSIONS: Higher inflammatory reaction and weaker clinical recovery was associated with lower insurance coverage population undergoing open mitral valve procedure but not ASD/PFO interventional occlusion procedure.

Artesunate Attenuated the Progression of Abdominal Aortic Aneurysm in a Mouse Model.

BACKGROUND: The inflammatory reaction is an important mechanism of pathogenesis of abdominal aortic aneurysm (AAA). Artesunate (AS) has been found to have anti-inflammatory effects in cardiovascular disease. The purpose of this study was to investigate whether AS could inhibit the development of AAA. MATERIALS AND METHODS: AngII infused ApoE (-/-) male mice were selected as AAA model. Mice were spilt into three groups, the experimental control group (AngII), the AS treatment group (AngII + AS) and the negative control group (Vehicle) with 14 in each group. Daily administration of AS (100 mg/kg/d) or vehicle performed 3 day before the perfusion. At the end of the 28-day experiment, animal ultrasound and electronic digital caliper were used to measure the diameter of abdominal aorta. Histologic assays were performed to observe the microstructure of the aorta wall. Immunofluorescence staining was performed to detect inflammatory cells, as well as the levels of matrix metalloproteinases (MMPs). The transcription of cytokines and adhesion molecules were investigated by real-time fluorescence quantitative PCR (qPCR). Western blotting was performed to determine whether the NF-κB pathway is involved in the mechanism. RESULTS: While AS failed to reduce the incidence of AAA, AS effectively reduced the diameter of AAA independently of blood pressure effects. Immunofluorescence detection showed that AS effectively reduced the levels of CD45+ cells and MAC3+ macrophages as well as MMP-2 and MMP-9. qPCR revealed that AS reduced mRNA transcription levels of MMP-2, MMP-9, the cytokine IL-1ß, TNF-α, adhesion molecules ICAM-1, VCAM-1. AS decreased the levels of NF-κB signaling pathway in aorta. CONCLUSIONS: AS can attenuate the development of AAA in mice. The possible mechanism is anti-inflammation.

Endothelial dysfunction in COVID-19 calls for immediate attention: the emerging roles of the endothelium in inflammation caused by SARS-CoV-2.

The COVID-19 pandemic has caused numerous deaths around the world. A growing body of evidence points to the important role of overwhelming inflammatory responses in the pathogenesis of COVID-19 and the effectiveness of anti-inflammation therapy against COVID-19 is emerging. In addition to affecting the lungs, COVID-19 can be a severe systemic inflammatory disease that is related to endothelial dysfunction. We are calling for closer attention to endothelial dysfunction in COVID-19 not only for fully revealing the pathogenic mechanism of COVID-19 but also for properly adjusting the strategy of clinical intervention.

Inhibition of microRNA-10b-5p up-regulates HOXD10 to attenuate Alzheimer's disease in rats via the Rho/ROCK signalling pathway.

OBJECTIVE: It is believed that microRNAs (miRNAs) participate in the pathogenesis of Alzheimer's disease (AD), but the specified function of miR-10b-5p in the disease has not been thoroughly understood. Thereafter, this research aimed to assess the function of miR-10b-5p in AD. METHODS: Rat AD models were established by injected with amyloid-ß1-42 (Aß1-42), which were mainly treated with lentivirus-miR-10b-5p inhibitor, or lentivirus-overexpressed homeobox D10 (HOXD10). MiR-10b-5p, HOXD10, RhoA, ROCK1 and ROCK2 expression in rat hippocampal tissues were determined. Afterwards, the behaviour of rats was tested, and neuronal apoptosis, pathological injury, and inflammatory factors and oxidative stress-related factors were all assessed. Finally, the target relation between miR-10b-5p and HOXD10 was detected. RESULTS: MiR-10b-5p was upregulated while HOXD10 was downregulated, and the Rho/ROCK signalling pathway was activated in hippocampal tissues of rats with AD. Inhibition of miR-10b-5p could attenuate the neuronal apoptosis, pathological injury, inflammation reaction, and oxidative stress by elevating HOXD10 and inhibiting the Rho/ROCK signalling pathway in AD rats. Moreover, HOXD10 was targeted by miR-10b-5p. CONCLUSION: Inhibited miR-10b-5p decelerated the development of AD by promoting HOXD10 and inactivating the Rho/ROCK signalling pathway, and our findings may contribute to the exploration of AD treatment.

Endothelial dysfunction in COVID-19 calls for immediate attention: the emerging roles of the endothelium in inflammation caused by SARS-CoV-2 / 医学前沿

The COVID-19 pandemic has caused numerous deaths around the world. A growing body of evidence points to the important role of overwhelming inflammatory responses in the pathogenesis of COVID-19 and the effectiveness of anti-inflammation therapy against COVID-19 is emerging. In addition to affecting the lungs, COVID-19 can be a severe systemic inflammatory disease that is related to endothelial dysfunction. We are calling for closer attention to endothelial dysfunction in COVID-19 not only for fully revealing the pathogenic mechanism of COVID-19 but also for properly adjusting the strategy of clinical intervention.

Effects of inflammation and immunoregulatory responses in the formation of peritoneal adhesion / 国际生物医学工程杂志

Peritoneal adhesion (PA) is a high morbidity complication after surgical procedures, with serious clinical consequences and requiring substantial medical expenditure. The pathogenesis of PA is complex and is still not very clear. Clinically, it is mainly treated by optimizing surgical protocols, using anti-adhesion drugs and biomaterial barriers. Although these methods have shown certain preventive effects, the effectiveness needs to be further improved. Elucidating the mechanism of PA formation is the basis and premise for preventing its occurrence. In the process of PA formation, a variety of inflammatory cells, inflammatory factors play important roles. In this paper, the mechanism of inflammation and immunoregulatory responses in the formation of adhesions in the peritoneal cavity was reviewed, in order to provide a reference for the improvement of PA prevention strategies.

ResolvinD1 Protects the Airway Barrier Against Injury Induced by Influenza A Virus Through the Nrf2 Pathway.

Airway barrier damage and excessive inflammation induced by influenza A virus (IAV) are associated with disease progression and prognosis. ResolvinD1 (RvD1) is a promising lipid mediator with critical protection against infection in the lung. However, whether RvD1 protects against IAV-induced injury and the underlying mechanisms remain elusive. In this study, primary normal human bronchial epithelial (pNHBE) cells were isolated and co-cultured with IAV and/or RvD1. Then, the expressions of E-cadherin, Zonula occludins-1, inflammatory mediators and proteins in Nrf2-dependent pathway were detected. To further explore the mechanisms, Nrf2 short hairpin RNA (Nrf2 shRNA) was applied in pNHBE cells. Furthermore, mice were infected with IAV, and were subsequently treated with RvD1. We found that IAV downregulated expressions of E-cadherin, Zonula occludins-1, Nrf2 and HO-1, upregulated the phosphorylation of NF κ B p65 and IKBα, levels of IL-8 and TNF-α, as well as ROS production. RvD1 reversed these damaging effects induced by IAV. However, when Nrf2 expression was suppressed with shRNA in pNHBE cells, the protective effects of RvD1 on IAV-induced injury were inhibited. In vivo studies further demonstrated that RvD1 could alleviate barrier protein breakdown and reduce airway inflammatory reactions. Collectively, the study demonstrated that RvD1 could play dual beneficial roles in protecting airway epithelium barrier function and reducing inflammation via the Nrf2 pathway, which may provide a better treatment option for influenza A virus infection.

Advances in BPA-induced Oxidative Stress and Related Effects and Mechanisms in Liver, 1991-2017.

Bisphenol A (BPA) is a widely spreading environmental endocrine disruptor . Its characteristics, including small doses and frequent contact, make it easy to enter human body through drinking water, food, air and other pathways, leading to tumors, infertility, and liver damage. The present review summarizes the underlying mechanism of oxidative stress and its related effects induced by BPA in the liver. The progress of the mechanism for oxidative stress induced by BPA is summarized, including mitochondrial dysfunction, lipid peroxidation and inflammation reaction, liver dyslipidemia, apoptosis, and cell death mechanism. In the future, it is necessary to elucidate the molecular mechanisms and timing of oxidative stress to clarify the effects on different exposures to different genders and growth stages. Besides, studying the toxic effects on BPA surrogates, BPA metabolites and BPA combined with other pollutants in the environment is beneficial to clarify the environmental and human health effects of BPA and provide technical reference for the development of practical control measures.

Improvement Effects of Water Extract of Astragalus membranaceus on Chronic Renal Failure Model Rats and Its Effects on MAPK Signaling Pathway / 中国药房

OBJECTIVE： To investigate the improvement effects of water extract of Astragalus membranaceus on chronic renal failure （CRF） model rats and its effects on MAPK signaling pathway， and to investigate possible mechanism. METHODS： Male SD rats were randomly divided into control group （10 rats） and model group （50 rats）. CRF model was established by intragastric administration of 25％ Adenine suspension 200 mg/kg （once a day， for consecutive 28 d）. After modeling， modeling group was randomly divided into model group， benazepril group （positive control， 2 mg/kg）， A. membranaceus water extract low-dose， medium-dose and high-dose groups （1.5， 3， 6 g/kg，by crude drug）， with 10 rats in each group. Control group and model group were given constant volume of normal saline intragastrically， and administration groups were given relevant medicine intragastrically， once a day， for consecutive 28 d. Twelve hours after last medication， the contents of serum renal function indexes （serum creatinine， urea nitrogen， uric acid） were determined by colorimetry. ELISA method was used to detect the levels of serum inflammatory factors （IL-1β， IL-6 and TNF-α）. The activity or content of oxidative stress related indexes （SOD， CAT and MDA）in renal tissue of rats were determined by hydroxylamine method， visible spectrophotometry method and thiobarbituric acid method. The mRNA expression of apoptosis-related factors （Bax， Bcl-2， Caspase-3） in renal tissue， MAPK signaling pathway-related regulatory protein p38 MAPK， phosphorylated p38 MAPK（p-p38 MAPK）， ERK1/2， phosphorylated ERK1/2 （p-ERK1/2）， JNK and phosphorylated JNK （p-JNK） were determined by real- time PCR and Western blotting assay. RESULTS： Compared with control group， the contents of renal function indexes and the levels of inflammatory factors in serum， MDA content， mRNA expression ratio of Bax and Bcl-2 （Bax/Bcl-2）， mRNA related expression of Caspase-3， related expression of phosphorylation product of MAPK signaling pathway-related regulatory proteins （p-p38 MAPK， p-JNK， p-ERK1/2） in renal tissue were increased significantly in model group， while the activities of SOD and CAT were decreased significantly in renal tissue （P＜0.01）. Compared with model group， the contents of renal function indexes and the levels of inflammatory factors in serum， Bax/Bcl-2， related expression of phosphorylation product of MAPK signaling pathway-related regulatory proteins in renal tissue were decreased significantly in administration groups as well as MDA content and mRNA related expression of Caspase-3 were decreased significantly in benazepril group and A. membranaceus water extract medium-dose and high-dose groups； the activities of SOD and CAT in renal tissue were increased significantly in benazepril group and A. membranaceus water extract medium-dose and high-dose groups （P＜0.05 or P＜0.01）. MDA content and Bax/Bcl-2 of benazepril group were significantly lower than those of A. membranaceus water extract high-dose group （P＜0.05）. CONCLUSIONS： A. membranaceus water extract has a certain improvement effect on CRF model rats， and inhibit its inflammatory reaction， oxidant stress and cell apoptosis， the mechanism of which may be associated with inhibiting the expression of MAPK signaling pathway-related regulatory proteins.

Study on Improvement Effects of Ethanol Extract of the Root of Anacyclus pyrethrum on Cough Variant Asthma Model Rats / 中国药房

OBJECTIVE： To observe the improvement effects of ethanol extract of the root of Anacyclus pyrethrum （EEAP） on cough variant asthma （CVA） model rats. METHODS： Male SD rats were randomly divided into control group， model group， prednisone acetate group （positive control， 250 mg/kg）， EEAP low-dose， medium-dose and high-dose groups （160， 320， 640 mg/kg， by the weight of EEAP）， with 10 rats in each group. Except for control group， other group was given 1 mg/mL ovalbumin （OVA）-Freunds adjuvant complete solution subcutaneously， and aerosol inhalation of 1％ OVA-normal saline （once a day， 20 min each time， 15 d） to induce CVA. After last inhalation， control group and model group were given constant volume of water intragastrically； administration groups were given relevant medicine intragastrically， once a day， for consecutive 30 d. General symptoms of rats were observed in each group during experiment. The airway sensitivity of rats in each group was investigated by capsaicin cough provocation test， and the cough times were recorded. The contents of SOD and TNF-α in serum were determined by ELISA. The morphological characteristics of lung tissue were observed by HE staining. The number of eosinophils and leucocytes in alveolar lavage fluid was recorded by Rayleigh staining. RESULTS： Rats in the control group breathed smoothly， responded quickly and had glossy coat. The rest of the groups showed restlessness， cough， shortness of breath and other symptoms after antigen stimulation. Compared with control group， the congestion and edema of bronchial wall and infiltration of inflammatory cells in the lung tissue were observed in model group； the cough times increased significantly； serum content of TNF-α， eosinophil and leukocyte counts in alveolar lavage fluid increased significantly， and serum content of SOD decreased significantly （P＜0.05）. After treatment， above symptoms of rats were alleviated to varying degrees in administration groups， and the cough times were significantly reduced； the serum contents of TNF-α as well as eosinophil and leukocyte counts in alveolar lavage fluid were significantly reduced； the serum contents of SOD was increased significantly， but the cough times of EEAP groups were significantly higher than that of prednisone acetate group （P＜0.05）. CONCLUSIONS： EEAP may show the anti-inflammatory and antiasthmatic effects by inhibiting the secretion of TNF-α， increasing the content of SOD and inhibiting inflammatory cell infiltration.

MicroRNA-495 Ameliorates Cardiac Microvascular Endothelial Cell Injury and Inflammatory Reaction by Suppressing the NLRP3 Inflammasome Signaling Pathway.

BACKGROUND/AIMS: In recent years, microRNA-495 (miR-495) has been reported to be a tumor-suppressor miR that is down-modulated in cancers. However, its potential mechanism remains unknown. Therefore, this study aimed to demonstrate the role of miR-495 in cardiac microvascular endothelial cell (CMEC) injury and inflammatory reaction by mediating the pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway. METHODS: Overall, 40 mice were assigned into myocardial ischemia/reperfusion injury (MIR) and sham groups. After model establishment, the levels of troponin T (TnT), troponin I (TnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase isoenzyme MB (CK-MB), myoglobin (MYO), tumor necrosis factor-alpha (TNF-α), and interleukin 1beta (IL-1ß) were detected by Enzyme-Linked Immunosorbent Assay (ELISA). Apoptosis was evaluated using Terminal deoxy (d)-UTP nick end labeling (TUNEL) staining, the level of NLRP3 protein was determined by immunohistochemical assay, and miR-495 was detected by in situ hybridization (ISH). The infarct size was determined using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The expression of miR-495 and the mRNA and protein levels of NLRP3, TNF-α, IL-1ß, IL-18 and caspase-1 were evaluated by RT-qPCR and western blot analysis. After transfection, the cells were treated with a miR-495 mimic, a miR-495 inhibitor, or siNLRP3. Cell proliferation was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cell cycle and apoptosis by flow cytometry. RESULTS: Mice with myocardial I/R injury had elevated levels of TnT, TnI, NT-proBNP, CK-MB, MYO, TNF-α and IL-1ß; enhanced cell apoptosis; increased expression of NLRP3, TNF-α, IL-1ß, IL-18 and caspase-1; and decreased miR-495 expression. MiR-495 was confirmed to target NLRP3. Moreover, miR-495 reduced the mRNA and protein levels of NLRP3, TNF-α, IL-1ß, IL-18 and caspase-1, inhibited cell apoptosis and decreased cells at the G0/G1 phase while improving cell proliferation and increasing cells at the S phase. However, the effects of NLRP4 were proved to be reciprocal. CONCLUSION: In conclusion, the current study indicated that miR-495 improved CMEC injury and inflammation by suppressing the NLRP3 inflammasome signaling pathway.

[Discussion of mechanism on acupoint embedding for obesity].

To explore the mechanism of acupoint embedding for obesity based on the western pathological mechanism of chronic low inflammatory response inducing the imbalance between"promoting inflammation"and"anti-inflammation"in immune reaction, and the pathological nature of deficient healthy qi and state of evil domination in the TCM theory induced by the"stagnation heat, phlegm heat, dampness heat, stasis heat"on the basis of qi deficiency. The mechanism may be improving the secretory disorder of adipose tissue and metabolic inflammatory response by the enhanced anti-inflammatory phagocytosis clearance ability in the immune system which is caused by the new inflammatory reaction under the stimulation of innate immune response pattern. The model of"inhibiting chronic low inflammation reaction through the innate immunity"may be an important mechanism of acupoint embedding for obesity.

Single-chain Fv Antibodies for Targeting Neurodegenerative Diseases.

BACKGROUND & OBJECTIVE: Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregates damage mitochondria and induce oxidative stress, resulting in neuronal cell death. Prolonged neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal protein aggregates without eliciting any adverse effects are the main treatment strategies. To overcome this, recent studies have deployed single- chain fragment variable antibodies (scFvs) to target the pathological protein aggregates, such as amyloid-beta (Aß) peptides, α-synuclein (α-syn) and Huntingtin (Htt). To date scFv has been effective at inhibiting abnormal protein aggregates formation in both in vitro and in vivo model system of AD, PD and HD. CONCLUSION: Currently active research is still ongoing to improve the scFv gene delivery technology, to further enhance brain penetration, intracellular stability, solubility and efficacy of scFv intrabody.

Discussion of mechanism on acupoint embedding for obesity / 中国针灸

To explore the mechanism of acupoint embedding for obesity based on the western pathological mechanism of chronic low inflammatory response inducing the imbalance between"promoting inflammation"and"anti-inflammation"in immune reaction, and the pathological nature of deficient healthy and state of evil domination in the TCM theory induced by the"stagnation heat, phlegm heat, dampness heat, stasis heat"on the basis of deficiency. The mechanism may be improving the secretory disorder of adipose tissue and metabolic inflammatory response by the enhanced anti-inflammatory phagocytosis clearance ability in the immune system which is caused by the new inflammatory reaction under the stimulation of innate immune response pattern. The model of"inhibiting chronic low inflammation reaction through the innate immunity"may be an important mechanism of acupoint embedding for obesity.

Comparison of postoperative pain and inflammation reaction in dogs undergoing preventive laparoscopic-assisted and incisional gastropexy.

This study compared the effects of postoperative pain and inflammation reaction after preventive laparoscopic-assisted gastropexy (LAG) and incisional gastropexy (IG) in 10 clinically normal Beagles. Surgical time, incision length, visual analog scale (VAS) score, University of Melbourne Pain Scale (UMPS) score, and plasma C-reactive protein (CRP), plasma cortisol (COR), and serum interleukin-6 (IL-6) levels were evaluated. The VAS and UMPS scores and COR and IL-6 levels were recorded at 0.5, 1, 2, 4, 8, 12, 18 and 24 hr after surgery. CRP level was recorded at 12, 24 and 48 hr after surgery. The VAS and UMPS scores showed no significant intergroup differences. Compared to IG, LAG had significantly lower surgical time (45 ± 9.91 min vs 64 ± 5.30 min; P<0.05), incision length (46 ± 8.21 mm vs 129 ± 19.49 mm; P<0.05), CRP level (12 hr after surgery; 4.58 ± 1.58 mg/dl vs 12.4 ± 1.34 mg/dl; P<0.01), and COR level (1 hr after surgery; 10.79 ± 3.07 µg/dl vs 15.9 ± 3.77 µg/dl; P<0.05). IL-6 levels showed no significant intergroup differences at any time point. However, LAG resulted in lower IL-6 levels than did IG at all postoperative time points. Neither procedure resulted in significant surgical complications. LAG produced lower surgical stress than did IG, suggesting that LAG is a safe, minimally invasive, and highly useful technique for preventing canine gastric dilatation-volvulus. Nevertheless, since this study used experimental models, its usefulness should be evaluated in future cases.