Humans ; Myocardium ; Stem Cell Transplantation ; Stem Cells ; Tissue Engineering

Catheter Ablation ; methods ; Child ; Epicardial Mapping ; Female ; Heart Aneurysm ; complications ; surgery ; Humans ; Tachycardia, Ventricular ; complications ; surgery

Aim To investigate the effects of emodin on the contraction of gallbladder smooth muscle(GBSM)and the L-type calcium current in GBSM cells.Methods Gallbladder muscle strips were obtained from adult guinea pigs and the resting tension was recorded.Gallbladder smooth muscle cells were isolated by enzymatic digestion,and calcium current was recorded by the whole-cell patch clamp method.Results Emodin-induced contraction of GBSM was significantly attenuated by pretreatment with nifedipine.Emodin increased the L-type calcium current in a dose-dependent manner.When 10 ?mol?L-1 emodin was applied to GBSM cells,the amplitude of L-type calcium current at +10 mV was enhanced by(45.2?2.26)%.In the presence of PKC inhibitor,staurosporine,emodin did not significantly affect the calcium current.Conclusion Emodin enhances L-type calcium current via PKC-dependent pathway and promotes gallbladder contraction.

Objective To investigate the relationship between peripheral blood circulating follicular helper T cells and antibody-secreting B cells in patients with ankylosing spondylitis (AS). The role of circulating follicular helper T cells and antibody-secreting B cells in the pathogenesis of AS were explored. Methods Flow cytometry was used to detect the levels of peripheral blood CD4 +CXCR5+ T (cTfh), CD4+CXCR5+PD-1+ T, CD4+CXCR5+ICOS+ T, CD19+ B, CD19+CD38+ B cells in 59 patients with AS (including 36 cases of active AS patients and 23 cases of inactive AS patients). In addition, twenty healthy persons were selected as the controls. Data analysis were performed by independent-sample t test, One way ANOVA analysis, Pearson's and Spearman's correlation test. Results The percentages of cTfh [(26.8 ±10.4)%], CD4+CXCR5+PD-1+T [(12.1±14.0)%], CD4+CXCR5+ICOS+T [(13.6±9.5)%], CD19+CD38+B [(80.7±13.0)%] in the peripheral blood of AS group were significantly higher than healthy controls [(15.6 ±4.5)%, (6.4 ±2.4)%, (9.4 ± 4.5)%, (68.2±13.0)%] (t=6.663, P<0.01; t=2.999, P<0.01; t=2.573, P<0.05; t=2.712, P<0.01). The percentages of cTfh in the active AS group [(30.2 ±11.0)%] were significantly higher than those in the inactive AS group [(21.4±6.5)%] and HC (t=3.444, P<0.01;t=7.004, P<0.01). The percentage of CD19+CD38+B[(85.1±10.0)%] in the peripheral blood of active AS group was significantly higher than that of the inactive AS group [(73.8 ±14.2)%] and HC (t=3.561, P<0.01;t=5.410, P<0.01). The relationship between Bath AS disease activity index (BASDAI) and the percentage of cTfh, CD19+CD38+B was a positive correlation (r=0.442, P<0.01; r=0.405, P=0.001), and significant positive correlation was observed between the percentages of cTfh and CD19+CD38+B cells (r=0.420, P=0.001). Conclusion CD4+CXCR5+cTfh cells are significantly increased in peripheral blood in AS patients with aberrant CD19+CD38+ antibody-secreting B cells, suggesting that cTfh and CD19+CD38+antibody-secreting B cells may play an important role in the pathogenesis of AS .

Asialoglycoprotein receptor (ASGPR) is highly expressed on the surface of parenchymal liver cells. It can specifically recognize and bind to desialylated glycoproteins which contain terminal galactose or N-acetylgalactosamine residues, and endocytosed by clathrin-mediated endocytosis, transported and then degraded in lysosome. Based on this character, ASGPR mediated liver-targeted drug delivery is likely to increase drug distribution, reduce potential side effects and lower dose. This article reviewed the expression, structure, ligand binding and endocytosis of ASGPR, and summarized the design and optimization of ASGPR ligands and the release strategies. Finally, we put forward some expects about the clinical drug development for ASGPR.

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg^-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.

Adult ; Glutathione Peroxidase ; blood ; Hearing Tests ; Humans ; Male ; Malondialdehyde ; blood ; Military Personnel ; Noise, Occupational ; adverse effects

OBJECTIVETo observe the clinical effects of lipid-reducing red rice minute powder (LRRMP) on the levels of blood lipids, carotid artery intima-media thickness (IMT), and the plaque integral of hyperlipidemia patients complicated with carotid atherosclerosis.

METHODSThis study was conducted from April 2005 to April 2006 according to inclusion criteria. Sixty hyperlipidemia patients complicated with carotid atherosclerosis were randomly assigned to the treatment group (20 cases), the Chinese medicine control group (CM control group, 20 cases), and the Western medicine control group (WM control group, 20 cases). They were recruited from the community of secondary machine tool factory of Jinan. Patients in the treatment group took LRRMP (175 mg/pill), one pill each time, twice daily. Patients in the CM control group took Xuezhikang Capsule (300 mg/pill), 2 pills each time, twice daily. Patients in the WM control group took Lovastatin Tablet (20 mg/tablet), 1 tablet each time, once daily. The course of treatment was 6 successive months for all. They avoided taking any lipid-regulating or anti-atherosclerotic drugs during the therapeutic course. The changes of Chinese medicine symptom scores, serum TC, TG, LDL-C, and HDL-C levels, IMT of the carotid artery, and the plaque integral before and after treatment were observed.

RESULTSAfter 6 months of treatment the Chinese medicine symptom scores reduced in each group ( P<0.05 or P<0.01), and the treatment group was superior to WM control group (P<0.05). Serum TC, TG and LDL-C levels were significantly lowered (P<0.05 or P<0.01), showing no significant difference in inter-group comparison (P>0.05). There was no statistical significance of the serum HDL-C level in each group (P>0.05). The IMT and the plaque integral significantly reduced (P<0.05, P<0.01), showing no statistical difference among all groups. One patient in the WM control group dropped out because of transaminase elevation. No serious adverse reaction correlated with the drugs occurred during the therapeutic course in the rest two groups.

CONCLUSIONSLRRMP showed definite effects on lipid-regulating and anti atherosclerosis. Its effects were equivalent to Xuezhikang Capsule and Lovastatin Tablet. Besides, it was safe and economic, and deserved further studies.

Aged ; Carotid Artery Diseases ; blood ; complications ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hyperlipidemias ; complications ; drug therapy ; Lipids ; blood ; Male ; Middle Aged ; Phytotherapy

Objective To evaluate the role of Janus kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) signaling pathway in sevoflurane postconditioning-induced inhibition of mitochondrial permeability transition pore (mPTP) opening during myocardial ischemia-reperfusion (I/R)in rats.Methods Sixty pathogen-free healthy male Sprague-Dawley rats,weighing 250-300 g,were divided into 4 groups (n=15 each) using a random number table:I/R group,sevoflurane postconditioning group (group SP),AG-490 group (group AG) and sevoflurane postconditioning plus AG-490 group (group SP+AG).Myocardial I/R was induced by 30 min ligation of the left anterior descending branch of coronary artery followed by 120 min reperfusion.In group SP,2.8％ sevoflurane was inhaled for 15 min starting from 2 min before reperfusion.JAK2 inhibitor AG-490 3 mg/kg was intravenously injected at 10 min before reperfusion in group AG.In group SP+AG,AG-490 3 mg/kg was intravenously injected at 10 min before reperfusion,and 2.8％ sevoflurane was inhaled for 15 min starting from 2 min before reperfusion.At 15 min of reperfusion,5 rats were sacrificed and myocardial specimens were obtained for determination of the expression of JAK2,phosphorylated JAK2 (p-JAK2),STAT3 and phosphorylated STAT3 (p-STAT3)in myocardial tissues by Western blot.The ratios of p-JAK2 to JAK2 expression (p-JAK2/JAK2) and pSTAT3 to STAT3 expression (p-STAT3/STAT3) were calculated.Five rats were sacrificed at the end of reperfusion for measurement of myocardial infarct size.The left 5 rats were selected and sacrificed,myocardial specimens were obtained,and the opening of mPTP was detected by a calcein-cobalt quenching method.Results Compared with group I/R,the myocardial infarct size and mPTP opening were significantly decreased,and JAK2/p-JAK2 and STAT3/p-STAT3 were increased in group SP (P＜0.05),and no significant change was found in the parameters mentioned above in SP+AG and AG groups (P＞0.05).Compared with group SP,the myocardial infarct size was significantly enlarged,the extent of mnPTP opening was aggravated,and JAK2/p-JAK2 and STAT3/p-STAT3 were decreased in SP+AG and AG groups (P＜0.05).Conclusion The mechanism by which sevoflurane postconditioning inhibits the opening of mPTP during myocardial I/R is related to activation of JAK2-STAT3 signaling pathway in rats.

AIM: To observe the expression change of growth and differentiation factor 10 ( GDF10 ) in the spinal cord of the rats with neuropathic pain .METHODS:Male SD rats (n=60) were used.The neuropathic pain was induced by ligation of left L 5 spinal nerves of the animals .The paw withdrawal threshold was detected 1 d before surgery , and 0 d, 1 d, 3 d, 10 d and 21 d after surgery.The changes of GDF10 in the dorsal horn of L5 spinal cord were detected by immunofluorescence staining and Western blot .RESULTS:The paw withdrawal threshold of the rats with spinal nerve ligation was decreased from 1 d after surgery until 3 d with obvious difference compared with the na ve rats ( P<0.05 ) , continuously decreased until 10 d, and then stabilized at 21 d.The GDF10 was located in the cytoplasm of the neurons in the dorsal horn of L5 spinal cord detected by immunofluorescence staining .The expression of GDF10 in L5 dorsal horn de-tected by immunofluorescence staining was reduced after surgery , significantly decreased from 10 d ( P<0.05) until more than 21 d after surgery in spinal nerve ligation group compared with na ve group.GDF10 in L5 spinal cord detected at 10 d after surgery by Western blot was significantly down-regulated in spinal nerve ligation group compared with na ve group (P<0.05).CONCLUSION:Spinal nerve ligation induces the decrease in GDF 10 expression in spinal dorsal horn .The down-regulation of GDF10 may contribute to the regulation of hyperpathia caused by mechanical stimulation after the injury of spinal nerve .