This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.
Rats ; Animals ; Mitophagy ; Alzheimer Disease/genetics* ; Powders ; Protein Kinases/metabolism* ; Ubiquitin-Protein Ligases/metabolism*

With the ongoing epidemic of the Coronavirus disease in China and the widespread development of radiotherapy, radiation-induced lung injury has gradually become a clinical problem that has attracted much attention. The pathogenesis of radiation-induced lung injury is complex, involving an imbalance in the polarization state of alveolar macrophages and an upregulation of alveolar epithelial cell apoptosis. Previous studies have shown that vitamin C is an important antioxidant substance, and preventive use of vitamin C can effectively treat acute lung injury. However, whether prophylactic use of vitamin C can effectively prevent or treat lung injury caused by radioactive substances, and its specific molecular mechanism remains to be studied. The purpose of this study is to investigate whether the prophylactic use of vitamin C to treat the alveolar macrophage cell line RAW 264. 7 and human lung epithelial cells BEAS-2B can effectively control the abnormal polarization of macrophages and the abnormal apoptosis of lung epithelial cells. This study found that after 4 weeks and 8 weeks of radioactive X-ray irradiation, the expression of macrophage M1 polarization state markers such as iNOS was significantly up-regulated (P< 0. 05), and preventive use of vitamin C to treat macrophages and lung epithelial cells can alleviate the polarization state disorder of macrophages and the apoptosis of alveolar epithelial cells caused by external radiation exposure, which is manifested in the down-regulation of the expression of Cleaved Caspase3. In addition, the preventive application of vitamin C treatment can inhibit the MAPK signaling pathway activated by external radiation exposure. Further experimental results showed that the inhibition of the MAPK pathway is the key to inhibiting the M1 polarization of macrophages and the apoptosis of lung epithelial cells. In summary, our findings suggest that vitamin C may play a protective role in acute radiation-induced lung injury by inhibiting macrophage M1 polarization/ promoting macrophage M2 polarization and alleviating alveolar epithelial cell apoptosis. This study will help to better understand the process and mechanism of the preventive effect of vitamin C, a common vitamin, on radiation-induced lung injury.

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg

This study investigated the mechanism of baicalin on lipopolysaccharide(LPS)/interferon γ(IFN-γ)-induced inflammatory microglia based on the triggering receptor expressed on myeloid cells 2(TREM2)/Toll-like receptor 4(TLR4)/nuclear factor kappaB(NF-κB) pathway. Specifically, LPS and IFN-γ were used to induce inflammation in mouse microglia BV2 cells. Then the normal group, model group, low-dose(5 μmol·L~(-1)) baicalin group, medium-dose(10 μmol·L~(-1)) baicalin group, high-dose(20 μmol·L~(-1)) baicalin group, and minocycline(10 μmol·L~(-1)) group were designed. Cell viability was detected by CCK-8 assay and cell morphology was observed under bright field. The expression of interleukin-1β(IL-1β), interleukin-4(IL-4), inducible nitric oxide synthase(iNOS), interleukin-6(IL-6), interleukin-10(IL-10), and arginase-1(Arg-1) mRNA was detected by real-time quantitative PCR, the protein expression of tumor necrosis factor-α(TNF-α), IL-1β, TREM2, TLR4, inhibitor kappaB-alpha(IκBα), p-IκBα, NF-κB p65 and p-NF-κB p65 by Western blot, and transfer of NF-κB p65 from cytoplasm to nucleus by cellular immunofluorescence. Compared with the normal group, most of the BV2 cells in the model group tended to demonstrate the pro-inflammatory M1 amoeba morphology, and the model group showed significant increase in the mRNA levels of IL-1β, IL-6, and iNOS, decrease in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), rise of the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.01), reduction in TREM2 protein expression, and increase in the expression of NF-κB p65 in nucleus. Compared with the model group, baicalin groups and minocycline group showed the recovery of BV2 cell morphology, significant decrease in the mRNA levels of IL-1β, IL-6 and iNOS, increase in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), reduction in the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.05), rise of TREM2 protein expression, and decrease in the expression of NF-κB p65 in nucleus. In summary, these results suggest that baicalin can regulate the imbalance between TREM2 and TLR4 of microglia and inhibit the activation of downstream NF-κB, thus promoting the polarization of microglia from pro-inflammatory phenotype to anti-inflammatory phenotype.
Animals ; Flavonoids ; Inflammation/genetics* ; Interferon-gamma ; Lipopolysaccharides/adverse effects* ; Mice ; NF-kappa B/metabolism* ; Toll-Like Receptor 4/metabolism*

Objective:To explore the long-term effect of Zhenzhu Tiaozhi capsule（FTZ） on hemoglobin A1c（HbA1c）in patients with type 2 diabetes mellitus （T2DM） based on real-world data. Method:T2DM patients who were provided with FTZ （FTZ group） and those receiving conventional hypoglycemic drugs （control group） were extracted from the hospital information system （HIS） of the First Affiliated Hospital of Guangdong Pharmaceutical University， followed by propensity score matching （PSM） for balancing the confounding factors between groups. With HbA1c as the efficacy evaluation index， the difference in efficacy between the two groups was compared using t-test and χ² test. For repeated measurement data of the same patient， the difference in efficacy and the stability of FTZ against HbA1c were analyzed by generalized estimating equation （GEE）. The factors that might affect the efficacy of FTZ against HbA1c were subjected to multivariate linear regression analysis （MLRA）， and the subgroup analyses were then conducted after the stratification of relevant factors. Result:There were 46 patients included in the FTZ group and 1 208 patients in the control group. PSM yielded 42 pairs of samples with balanced covariates between groups. As revealed by one-year observation， ① HbA1c in the FTZ group after treatment was 6.51%±1.09%. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. At the same time， the HbA1c compliance rate in the FTZ group was 73.8% after treatment. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. ② The GEE results showed that the post-treatment HbA1c levels in the two groups were not significantly different from each other. Moreover， the HbA1c level remained stable over treatment time. ③ MLRA and subgroup analyses results demonstrated that FTZ was more effective in patients with high baseline HbA1c ［β=-0.530，95% confidence interval（CI） -0.850～-0.209，P<0.01］ or those who were complicated with hypertension （β=-0.918，95%CI -1.614～-0.222，P<0.05）. Conclusion:In the real world， FTZ is able to control the blood sugar， and its effect is similar to those of conventional hypoglycemic drugs. Besides， it is capable of stabilizing the blood sugar for a long time.

Objective:To investigate the neuroprotective effects of Danggui Shaoyaosan （DSS） on APP_swe/PS1_ΔE9 transgenic （APP/PS1） mice and its mechanism related to circular RNA （circRNA）. Method:Totally twenty 6-month-old APP/PS1 mice were divided into model group and DSS group， and 10 C57BL/6 wild-type mice were set as the normal control group. The normal group and model group received the same volume of normal saline， and DSS group received drug by gavage administration， all for 8 weeks. The differentially expressed circRNA of APP/PS1 mice before and after DSS intervention was analyzed by circRNA sequencing to construct circRNA-miRNA mRNA interaction network. The results of cricRNA sequencing were then verified by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of phosphoinositide 3-kinase （PI3K）， p-PI3K， protein kinase B1 （Akt1）， p-Akt1， B lymphocytoma-2 （Bcl-2）， and Bcl-2-Associated X protein （Bax） in the hippocampus were detected by immunoblotting （Western blot）. The protein expression of Caspase-3 in the hippocampus was detected by immunohistochemistry and the level of apoptosis in the hippocampus was detected by the TUNEL method. Result:Compared with the model group， there were 90 differentially expressed circRNA after intervention with DSS， of which 46 were up-regulated and 44 down-regulated. Compared with the normal group， the expression levels of circRNA1398 and circRNA1399 in the model group decreased， and the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p increased. Compared with the model group， the expression levels of circRNA1398 and circRNA1399 in the DSS group were up-regulated， while the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p were down-regulated. Compared with the normal group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the model group decreased （P<0.05， P<0.01）， and the expression of Bax and Caspase in the model group increased （P<0.01）. Compared with the model group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the hippocampus of the DSS group increased （P<0.01）， and the protein expression of Bax and Caspase decreased （P<0.01）. Compared with the normal group， the apoptosis level in the hippocampus of the model group increased， with an apoptosis rate of （43.76±2.92）%. Compared with the model group， the apoptosis rate of DSS group was （24.64±3.39）%. Conclusion:DSS can activate PI3K/Akt pathway and inhibit apoptosis in hippocampal neurons of APP / PS1 mice， and play a neuroprotective role. The specific mechanism may be related to the regulation of circRNA1398 and circRNA1399 expression and the corresponding miRNA expression.

Objective:To know the exercise status of asthmatic in school-age, and to identify possible influen-cing factors.Methods:School-age children with a firm diagnosis of asthma were continuously included in Asthma Clinic of Allergy Department, Children′s Hospital Affiliated to Capital Medical University from January 2016 to January 2017.Patients who complain any symptoms during or after exercise with or without exercise limitation were assigned to the abnormal exercise group (ANE), and children who stated no symptoms and exercise limitation were defined as normal exercise group (NE), correspondingly.These data include age, gender, length of recurrent wheezing history, duration of treatment with inhaled corticosteroids (ICS), asthma control status, body mass index (BMI), pulmonary function parameters by spirometry and plethysmography that were collected and analyzed.Results:A total of 194 cases were included: 135 cases (69.6%) were well controlled, 39 cases (20.1%) were partially controlled, and 20 cases (10.3%) were uncontrolled.Totally, 95 cases (49.0%) were distributed in ANE group, while 99 cases (51.0%) were in NE group.Meanwhile, 111 patients (57.2%) had normal BMI, 32 patients (16.5%) were overweight, and 51 patients (26.3%) were obese.In the Logistic regression model of all cases, the worse asthma control level (partially controlled OR=4.77, 95% CI: 2.07-11.00, P<0.001, uncontrolled OR=10.02, 95% CI: 2.70-37.22, P=0.001) and higher BMI ( OR=1.15, 95% CI: 1.06-1.25, P=0.001) were closely associated with the significantly increased risk of exercise abnormality.Among the patients with normal BMI, ANE group had more cases with hyperinflation than normal exercise group (43.8% vs.19.0%, P=0.005). Conclusions:The results suggested that poor asthma control status and overweight/obesity are risk factors for exercise limitation, and excessive lung inflation may also affect exercise in children with asthma.

ObjectiveTo investigate the relationship between chronic inflammatory response induced by high-fat diet （HFD） and neurological dysfunction in Alzheimer's disease. MethodsTwelve-month-old C57BL/6J and APP_swe/PS1_ΔE9 （APP/PS1） male mice were randomly divided into 4 groups according to body weight： control group （C57BL/6J mice on standard chow， n=6）， control on HFD group （C57BL/6J mice on HFD， n=6）， dementia group （APP/PS1 mice on standard chow， n=6） and dementia on HFD group （APP/PS1 mice on HFD， n=6）. The mice were fed with standard chow or HFD for 6 weeks. Changes in body weight of mice were monitored weekly. Immunohistochemistry was used to examine the activation of microglias in hippocampus. RT-qPCR was performed to detect the expression of inflammatory factors including IL-1β， IL-6 and TNF-α. Nissl staining was conducted to observe the morphology of neuronal Nissl bodies in hippocampal CA1 region. The expression levels of NLRP3 and caspase-1 in hippocampus were measured by Western blot. Neuronal pyroptosis in hippocampus was determined by TUNEL and caspase-1 immunofluorescence double staining. ResultsThe 2×2 factorial design analysis revealed that high-fat diet enhanced the activation of hippocampal microglias， elevated the mRNA levels of inflammatory factors （IL-1β， IL-6 and TNF-α） and the relative protein level of NLRP3 （P<0.05）， and decreased Nissl bodies in hippocampal CA1 region. APP/PS1 genes enhanced the activation of microglias and the expression of IL-1β， TNF-α， NLRP3 and caspase-1 in hippocampus （P<0.05）. High-fat diet interacted with APP/PS1 genes in microglia activation and IL-1β mRNA expression enhancement （P<0.05）. In dementia mice， high-fat diet enhanced the expression of caspase-1/TUNEL in the hippocampus （P<0.05）， aggravated the neuronal pyroptosis， and worsened the damage of Nissl bodies in hippocampal CA1 region. ConclusionHigh-fat diet and APP/PS1 genes both can enhance the inflammatory response in mouse brain. High-fat diet can further aggravate the pyroptosis and impairment of neural function in dementia mice.

Objective: To analyze the dynamic changes in the expression and function of peripheral type Ⅱ innate lymphoid cell (ILC2) subpopulation and the activity of signal transducers and activators of transcription (STAT6) in children with hay fever during pollen season. Methods: A total of 10 patients with hay fever, 10 patients with house dust mite (HDM)-sensitized asthma and 12 healthy controls (HC) were enrolled in this study. Changes in peripheral ILC2 and the intracellular expression of Th2-related cytokines were detected by flow cytometry during and outside the pollen season. Peripheral Lin^- cell population was isolated from each group and cultured with the presence of IL-25 or IL-33 for 7 d. The concentrations of IL-5 and IL-13 in culture supernatants were measured by ELISA. Expression of phospho-STAT6 at protein level was quantified by Western blot. Results: Within the pollen season, the percentage of peripheral ILC2 cells was significantly higher in children with hay fever [(23.09±7.86)%] than in children with HDM-sensitized asthma [(6.84±3.85)%, P<0.05] and healthy children[(1.69±0.87)%, P<0.05]. In the non-pollen season, the peripheral ILC2 cells in children with hay fever presented a decreasing trend [(11.30±2.45)%], but was still higher than that in HDM-sensitized asthmatics [(3.76±1.96)%, P<0.05] and HC [(1.32±0.91)%, P<0.05] at the same time point. Moreover, peripheral IL-13⁺ ILC2 cells in children with hay fever [(6.94±3.16)% vs(4.17±1.98)%, P<0.05] and in HDM-sensitized asthmatics [(1.89±0.70)% vs(1.44±0.55)%, P<0.05] during the pollen season were significantly higher than those in the non-pollen season. After the in vitro stimulation with IL25 or IL-33, the levels of IL-5 and IL-13 in culture supernatants were both increased in children with hay fever and HDM-sensitized asthmatics, and a synergistic action was observed when IL25 and IL-33 were used in combination. Meanwhile, the protein level of phospho-STAT4 in Lin^- cells was significantly up-regulated in the hay fever group after stimulation with IL25 and IL-33. Conclusions During the pollen season, the abnormal number and function of ILC2 subpopulation in children with hay fever might be another cause of the occurrence of clinical symptoms in a short period of time or acute exacerbation.

Agkistrodon acutus is a traditional Chinese herb medicine which has immunological regulation,anti-tumor,anti-inflammatory and analgesic effects,which is mainly used for the treatment of rheumatoid arthritis,ankylosing spondylitis,sjogren's syndrome and tumors. In order to excavate more important functional genes from A. acutus,the transcriptome of the venom gland was sequenced by the Illumina Hi Seq 4000,and 32 862 unigenes were assembled. Among them,26 589 unigenes were mapped to least one public database. 2 695 unigenes were annotated and assigned to 62 TF families,and 5 920 SSR loci were identified. The majority of mapped unigenes was from Protobothrops mucrosquamatus in the NR database,which revealed their closest homology. Three secretory phospholipase A_2 with different amino acid sequences showed similar spatial structures and all had well-conserved active sites. The 3 D structural models of C-type lectin showed conserved glycosylation binding sites( Asn45). This study will lay the foundation for the further study of the function of snake venom protein,and promoting the development and utilization of genome resources from A. acutus.
Agkistrodon/genetics* ; Animals ; Crotalid Venoms ; Gene Expression Profiling ; Snake Venoms/genetics* ; Snakes ; Transcriptome