Aim To investigate the protective effects of methyl rosmarinate(MR)on myocardial injury in-duced by high-altitude hypoxia and explore its underly-ing mechanisms.Methods BALB/c mice were ran-domly divided into a control group,a model group,and low-,medium-,and high-dose MR groups(25,50,and 75 mg·kg-1,respectively).Except for the control group,all other groups were exposed to a hypobaric hypoxia chamber and administered MR via intraperitoneal injection daily for three days.After the experiment,myocardial tissues were collected for he-matoxylin and eosin(HE)staining to observe morpho-logical changes.Levels of malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)were measured to evaluate the anti-myocardial injury activity of MR.Network pharmacology was employed to predict drug-disease interaction targets,construct a protein-protein interaction(PPI)network,and identify core targets.Functional enrichment analysis was car-ried out using Gene Ontology(GO)and Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathways.Molecular docking was used to verify the binding affini-ty of MR to core targets,and Western blot was conduc-ted to detect the expression of related proteins.Results MR significantly alleviated myocardial injury caused by high-altitude hypoxia.Network pharmacology analy-sis identified EGFR,Bcl-2,STAT3,MMP9,ESR1,and MTOR as key targets.Molecular docking con-firmed strong binding between MR and these core tar-gets.Western blot results demonstrated that MR im-proved myocardial injury by regulating the expression of STAT3,Bax,and Bcl-2 proteins.Conclusion MR may exert its protective effects on high-altitude hypoxi-a-induced myocardial injury through a multi-target mechanism.

Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L^-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L^-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe²⁺, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe²⁺ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.
Animals ; Ferroptosis/drug effects* ; Estrogen Receptor alpha/genetics* ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Mice ; Humans ; Mice, Inbred C57BL ; Estradiol/metabolism*

Aim To investigate the protective effects of methyl rosmarinate(MR)on myocardial injury in-duced by high-altitude hypoxia and explore its underly-ing mechanisms.Methods BALB/c mice were ran-domly divided into a control group,a model group,and low-,medium-,and high-dose MR groups(25,50,and 75 mg·kg-1,respectively).Except for the control group,all other groups were exposed to a hypobaric hypoxia chamber and administered MR via intraperitoneal injection daily for three days.After the experiment,myocardial tissues were collected for he-matoxylin and eosin(HE)staining to observe morpho-logical changes.Levels of malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)were measured to evaluate the anti-myocardial injury activity of MR.Network pharmacology was employed to predict drug-disease interaction targets,construct a protein-protein interaction(PPI)network,and identify core targets.Functional enrichment analysis was car-ried out using Gene Ontology(GO)and Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathways.Molecular docking was used to verify the binding affini-ty of MR to core targets,and Western blot was conduc-ted to detect the expression of related proteins.Results MR significantly alleviated myocardial injury caused by high-altitude hypoxia.Network pharmacology analy-sis identified EGFR,Bcl-2,STAT3,MMP9,ESR1,and MTOR as key targets.Molecular docking con-firmed strong binding between MR and these core tar-gets.Western blot results demonstrated that MR im-proved myocardial injury by regulating the expression of STAT3,Bax,and Bcl-2 proteins.Conclusion MR may exert its protective effects on high-altitude hypoxi-a-induced myocardial injury through a multi-target mechanism.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

AIM To study the effects of Dianxianqing Granules on Tau protein in a mouse model of Alzheimer's disease (AD).METHODS The mice expressing P301S mutant Tau variant were randomly divided into the model group,the MCC950 group (NLRP3 inhibitor,10 mg/kg),the Dianxianqing Granules group (12.48 g/kg),the MCC950+Dianxianqing Granules group,in contrast to the C57BL/6 mice of the control group.After 5 months of administration,the mice had their learning and memory ability tested by Y maze test and Morris water maze test;their cerebral morphological changes observed by HE staining;their cerebral expressions of Caspase-1 and GSDMD proteins detected by immunohistochemical method;their expression of cerebral Tau protein detected by immunofluorescence;and their cerebral expressions of Tau,p-Tau (ser202),p-Tau (thr205),NLRP3,Caspase-1,IL-1β and IL-18 detected by Western blot.RESULTS Compared with the control group,the model group displayed decreased rate of spontaneous alternate reaction and times of crossing platform (P<0.05,P<0.01);abnormal hippocampal morphology,decreased number of neurons,increased cerebral positive expressions of Caspase-1 and GSDMD (P<0.05);deposition of a large number of brown granules in cytoplasm,and increased protein expressions of Tau,p-Tau (ser202),p-Tau (thr205),NLRP3,Caspase-1,IL-1βand IL-18 in the hippocampus and the cortex (P<0.05,P<0.01).Compared with the model group,the group intervened with Dianxianqing Granules demonstrated both increased rate of spontaneous alternate reaction and times of crossing platform (P<0.05);complete and normal morphology of the brain,a diversity of fine neurons,reduced cerebral positive expressions of Caspase-1 and GSDMD (P<0.05);and decreased protein expressions of Tau,p-Tau (ser202),p-Tau (thr205),NLRP3,Caspase-1,IL-1β and IL-18 in the hippocampus and the cortex (P<0.05,P<0.01).CONCLUSION Dianxianqing Granules may inhibit Tau protein expression in the mouse model of AD via NLRP3/Caspase-1 pathway.

AIM To study the effects of Dianxianqing Granules on Tau protein in a mouse model of Alzheimer's disease (AD).METHODS The mice expressing P301S mutant Tau variant were randomly divided into the model group,the MCC950 group (NLRP3 inhibitor,10 mg/kg),the Dianxianqing Granules group (12.48 g/kg),the MCC950+Dianxianqing Granules group,in contrast to the C57BL/6 mice of the control group.After 5 months of administration,the mice had their learning and memory ability tested by Y maze test and Morris water maze test;their cerebral morphological changes observed by HE staining;their cerebral expressions of Caspase-1 and GSDMD proteins detected by immunohistochemical method;their expression of cerebral Tau protein detected by immunofluorescence;and their cerebral expressions of Tau,p-Tau (ser202),p-Tau (thr205),NLRP3,Caspase-1,IL-1β and IL-18 detected by Western blot.RESULTS Compared with the control group,the model group displayed decreased rate of spontaneous alternate reaction and times of crossing platform (P<0.05,P<0.01);abnormal hippocampal morphology,decreased number of neurons,increased cerebral positive expressions of Caspase-1 and GSDMD (P<0.05);deposition of a large number of brown granules in cytoplasm,and increased protein expressions of Tau,p-Tau (ser202),p-Tau (thr205),NLRP3,Caspase-1,IL-1βand IL-18 in the hippocampus and the cortex (P<0.05,P<0.01).Compared with the model group,the group intervened with Dianxianqing Granules demonstrated both increased rate of spontaneous alternate reaction and times of crossing platform (P<0.05);complete and normal morphology of the brain,a diversity of fine neurons,reduced cerebral positive expressions of Caspase-1 and GSDMD (P<0.05);and decreased protein expressions of Tau,p-Tau (ser202),p-Tau (thr205),NLRP3,Caspase-1,IL-1β and IL-18 in the hippocampus and the cortex (P<0.05,P<0.01).CONCLUSION Dianxianqing Granules may inhibit Tau protein expression in the mouse model of AD via NLRP3/Caspase-1 pathway.

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO₁₅) and Shen (CO₁₀), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
Humans ; Depression/therapy* ; Magnetic Resonance Imaging/methods* ; Vagus Nerve Stimulation/methods* ; Brain/diagnostic imaging* ; Transcutaneous Electric Nerve Stimulation/methods* ; Vagus Nerve

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, First ; Iodide Peroxidase ; Cohort Studies ; Reproducibility of Results ; Fetal Development ; Fetal Weight ; Fetal Growth Retardation ; Ultrasonography, Prenatal

Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /10⁶ PBMCs) before ART, and droped rapidly (<400 copies /10⁶ PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/10⁶ PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.
China/epidemiology* ; DNA/therapeutic use* ; HIV Infections/drug therapy* ; HIV Seropositivity ; HIV-1/genetics* ; Humans ; Male ; Viral Load

Sarglanoids A-F, six new sesquiterpenoids belonging to eudesmane (1-5) and eremophilane (6) types, were isolated from the leaves of Sarcandra glabra, a famous traditional Chinese medicine (TCM). Their structures including absolute configurations were elucidated through extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Compounds 1-2 were rare N-containing eudesmane-type sesquiterpenoids. Compound 3 exhibited inhibitory activity against nitric oxide (NO) production in lipopolysaccharides (LPS)-induced RAW 264.7 cells with IC₅₀ values at 20.00 ± 1.30 μmol·L^-1. These findings provide scientific evidence for sesquiterpenoids as the material foundation of S. glabra.
Molecular Structure ; Plant Leaves ; Polycyclic Sesquiterpenes ; Seeds ; Sesquiterpenes/pharmacology*