Methylated Chromenoquinoline as a Novel Nucleus Fluorescent Probe for Nucleic Acid Imaging.

Two chromenoquinoline-based fluorescent probes 1a-b have been synthesized and investigated. Photofading behaviors of compounds 1a-b showed that at least 89% absorption remained after 6 h irradiating, meanwhile, many of ions and amino acids had negligible impacts on their fluorescence intensity, which meant they had excellent photostability and selectivity. Probes 1a-b exhibited strong absorption and emission in organic solvents with large fluorescence quantum yields, even in water probe 1a still had a relatively large fluorescence quantum yield (20%). Combined with DFT calculation, the influence of alkylation on optical properties of 1b was elucidated. In addition, the fluorescence intensity of probe 1b with red emission enhanced by 5.4-fold and 5.3-fold after DNA and RNA added, and the fluorescence quantum yield increased from 3% to 17% and 14%, respectively, but the neutral molecule 1a had no response to nucleic acid. Furthermore, confocal microscopy imaging of probes 1a-b showed that 1a targeted lipid droplets while the methylated probe 1b to nucleus in living HeLa cells. The results indicated that the subcellular targeting zone could be changed by alkylation of nitrogen atom on chromenoquinoline-based conveniently, which provided a new idea for designing and synthesizing new subcellular labeled probes.

An active glutamine/α-ketoglutarate/HIF-1α axis prevents pregnancy loss by triggering decidual IGF1+GDF15+NK cell differentiation.

Deficiency of decidual NK (dNK) cell number and function has been widely regarded as an important cause of spontaneous abortion. However, the metabolic mechanism underlying the crosstalk between dNK cells and embryonic trophoblasts during early pregnancy remains largely unknown. Here, we observed that enriched glutamine and activated glutaminolysis in dNK cells contribute to trophoblast invasion and embryo growth by insulin-like growth factor-1 (IGF-1) and growth differentiation factor-15 (GDF-15) secretion. Mechanistically, these processes are dependent on the downregulation of EGLN1-HIF-1α mediated by α-ketoglutarate (α-KG). Blocking glutaminolysis with the GLS inhibitor BPTES or the glutamate dehydrogenase inhibitor EGCG leads to early embryo implantation failure, spontaneous abortion and/or fetal growth restriction in pregnant mice with impaired trophoblast invasion. Additionally, α-KG supplementation significantly alleviated pregnancy loss mediated by defective glutaminolysis in vivo, suggesting that inactivated glutamine/α-ketoglutarate metabolism in dNK cells impaired trophoblast invasion and induced pregnancy loss.

Fluorescent probes based on acridine derivatives and their application in dynamic monitoring of cell polarity variation.

Polarity and viscosity, as important microenvironment parameters, play an essential role in cell metabolism. Therefore, 9-acridine carboxaldehyde reacted with cyano compounds to obtain polarity-sensitive probes 1a-b and viscosity-sensitive probes 1c-d. Among them, with the increase in solvent polarity, the maximum emission wavelength of acridine-dicyanoisophorone-based probe 1a red-shifted from 553 nm to 594 nm, the fluorescence quantum yield increased from 0.5% to 35.6%, and the fluorescence intensity enhanced 38 fold. The acridine-cyanofuranone based probe 1b also has a polarity response similar to 1a. Nevertheless, when the solution viscosity increased from 0.89 cP (100% water) to 856 cP (1% water), the fluorescence intensity of the acridine-tricyanodihydrofuran based probe 1c at 430 nm enhanced 5.6 times. The acridine-cyanobenzothiazole based probe 1d also had a viscosity response similar to 1c. In addition, probes 1a-b were used for further HeLa cell imaging experiments due to their good photostability and the results suggested that probe 1a could locate lipid droplets and probes 1b-c could stain lysosomes. Moreover, probes 1a-b could dynamically monitor the changes in intracellular polarity.

Near-infrared fluorescent probes based on a quinoxaline skeleton for imaging nucleic acids in mitochondria.

In this paper, two cationic probes 1a and 1b and a neutral dye 1c were successfully designed and synthesized according to the Knoevenagel condensation reaction, which combines the good optical properties of hemocyanine and the biocompatibility of nitrogen-containing heterocyclic rings based on a quinoxaline skeleton. Probes 1a and 1b showed an OFF-ON fluorescence response to nucleic acids with excellent selectivity. Specifically, the fluorescence intensity of probe 1a was enhanced by 18 and 133 times, respectively, along with the increase of DNA or RNA concentrations (0-600 µg mL-1). Furthermore, a good linear correlation between the fluorescence intensity of probes 1a and 1b and the concentrations of DNA or RNA (0-350 µg mL-1) was obtained. In particular, the maximum emission wavelengths of probes 1a and 1b reached the near-infrared region (660-664 nm) when DNA or RNA was detected, which might reduce the light damage to cells and facilitate cell experiments. Fluorescence imaging revealed that all three dyes could be localized in the mitochondria of HeLa cells. The difference was that probes 1a and 1b could stain the nucleic acid in the mitochondria, while dye 1c was only a neutral mitochondrial biomarker. The results indicated that probes 1a and 1b are promising in the development of low toxicity mitochondrial nucleic acid probes and are expected to be used in monitoring the normal state of mitochondrial nucleic acids for living cells, which will help improve the situation in that currently reported studies of fluorescent probes are mainly focused on the nucleic acids in the nucleus, but less so on DNA in the mitochondria.

Follistatin-like I promotes endometriosis by increasing proinflammatory factors and promoting angiogenesis.

Endometriosis (EMS) is a chronic benign inflammatory disease characterized by the growth of endometrial-like tissue in aberrant locations outside of the uterine cavity. Angiogenesis and abnormal immune responses are the fundamental requirements of endometriotic lesion survival in the peritoneal cavity. Follistatin-like I (FSTL1) is a secreted glycoprotein that exhibits varied expression levels in cardiovascular disease, cancer and arthritis. However, the role of FSTL1 in the development of EMS remains to be fully elucidated. Results of the present study demonstrated that the expression of FSTL1 was significantly increased in ectopic endometrial stromal cells (ESCs) and peritoneal fluid from patients with EMS, compared to the control group. Both conditions of hypoxia and estrogen treatment induced human ESCs to produce increased levels of FSTL1 and disco-interacting protein 2 homolog A (DIP2A). Furthermore, the expression levels of DIP2A, IL8 and IL1ß were increased in FSTL1 overexpressed HESCs. Additionally, FSTL1 treatment increased the proliferation of HUVECs in a dose-dependent manner in vitro and markedly increased the tube formation of HUVECs. Moreover, treatment with FSTL1 facilitated M1 polarization of macrophages, increased the secretion of proinflammatory factors and inhibited the expression of scavenger receptor CD36. Results of the present study suggested that the elevated expression of FSTL1 may play a key role in accelerating the development of EMS via enhancing the secretion of proinflammatory factors and promoting angiogenesis.

High glucose induces dysfunction of human umbilical vein endothelial cells by upregulating miR-137 in gestational diabetes mellitus.

Recent studies have revealed considerable dysfunction of vascular endothelial cells (VECs) and abnormal expression of microRNA (miR)-137 in women with gestational diabetes mellitus (GDM), and the aim of this study was to clarify the underlying mechanism and possible role of microRNA (miR)-137 in dysfunction of VECs during GDM. We found increased levels of miR-137 in the plasma of GDM women and high-glucose (HG)-exposed HUVECs. Upregulating miR-137 in HUVECs elevated the chemokine (C-C motif) ligand 2 (CCL2) secretion and enhanced the chemotaxis and adhesion of U937 and THP-1 (two human acute monocytic leukemia cell lines) cells to HUVECs in a co-culture system. Moreover, HG stimulation and/or overexpression of miR-137 inhibited the viability, upregulated the expression levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, and inflammatory cytokine interleukin (IL)-6, and downregulated the production of IL-8, vascular endothelial growth factor (VEGF), and angiogenesis of HUVECs in vitro. These results imply that up-regulated miR-137 by HG can restrict the viability and angiogenesis, promote the activation and inflammatory cytokine secretion of VECs, and stimulate the monocyte chemotaxis and adhesion to VECs. Ultimately, we have concluded that miR-137 is crucial to HG-induced VEC dysfunction and may be involved in pathology of GDM.

Solasodine inhibits human colorectal cancer cells through suppression of the AKT/glycogen synthase kinase-3ß/ß-catenin pathway.

Solasodine is a main active component isolated from Solanum incanum L. that performs a wide range of functions containing anti-oxidant, anti-infection, and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. The results show that solasodine prohibited CRC cell proliferation dose- and time-dependently and impeded CRC cell motility by downregulating MMPs. Solasodine was also found to fuel caspase-cascade reaction and increase the ratio between Bax and Bcl-2 so as to induce CRC cell apoptosis. When cells were pretreated with AKT activator (insulin-like growth factor-1) followed by solasodine, the solasodine-induced apoptosis was partially abrogated by insulin-like growth factor-1. Moreover, solasodine hindered tumor development and stimulated similar mechanisms in vivo. In general, our study provides the first evidence that solasodine has a suppressive effect on CRC cells and that this agent may be a novel therapeutic drug for CRC treatment.

Self-Assembled Polymeric Ionic Liquid-Functionalized Cellulose Nano-crystals: Constructing 3D Ion-conducting Channels Within Ionic Liquid-based Composite Polymer Electrolytes.

Composite polymeric and ionic liquid (IL) electrolytes are some of the most promising electrolyte systems for safer battery technology. Although much effort has been directed towards enhancing the transport properties of polymer electrolytes (PEs) through nanoscopic modification by incorporating nano-fillers, it is still difficult to construct ideal ion conducting networks. Here, a novel class of three-dimensional self-assembled polymeric ionic liquid (PIL)-functionalized cellulose nano-crystals (CNC) confining ILs in surface-grafted PIL polymer chains, able to form colloidal crystal polymer electrolytes (CCPE), is reported. The high-strength CNC nano-fibers, decorated with PIL polymer chains, can spontaneously form three-dimensional interpenetrating nano-network scaffolds capable of supporting electrolytes with continuously connected ion conducting networks with IL being concentrated in conducting domains. These new CCPE have exceptional ionic conductivities, low activation energies (close to bulk IL electrolyte with dissolved Li salt), high Li+ transport numbers, low interface resistances and improved interface compatibilities. Furthermore, the CCPE displays good electrochemical properties and a good battery performance. This approach offers a route to leak-free, non-flammable and high ionic conductivity solid-state PE in energy conversion devices.

ESIPT-based fluorescent enhanced probes prompted by methylated ß-cyclodextrin for the detection of thiophenols.

Thiophenol and its derivatives are compounds with high toxicity to organisms and environmental pollution, so it is necessary to detect the level of thiophenols in the environment and biological samples. The probes 1a-b were obtained by introducing the 2,4-dinitrophenyl ether group into diethylcoumarin-salicylaldehyde based compounds. And they can form host-guest compounds with methylated ß-cyclodextrin (M-ß-CD), the association constants of inclusion complexes are 49.2 M-1, 125 M-1 respectively. The fluorescence intensities of probes 1a-b at 600 nm (1a) and 670 nm (1b) increased significantly in thiophenols detection. Meanwhile, with the addition of M-ß-CD, the hydrophobic cavity of M-ß-CD significantly increased the fluorescence intensity of probes 1a-b, thus the detection limits of probes 1a-b to thiophenols were reduced from 410 nM, 365 nM to 62 nM, 33 nM respectively. Whereas, the good selectivity and short response time of probes 1a-b towards thiophenols was not affected in the presence of M-ß-CD. Moreover, probes 1a-b were used for further water sample detection and HeLa cell imaging experiments due to their good response to thiophenols and the results suggested that probes 1a-b had the potential to detect the content of thiophenols in water samples and living cells.

PrPC Promotes Endometriosis Progression by Reprogramming Cholesterol Metabolism and Estrogen Biosynthesis of Endometrial Stromal Cells through PPARα Pathway.

Endometriosis (EMs) is characterized as an estrogen-dependent disease. Whereas, the underlying mechanism for activated estrogen biosynthesis in EMs lesions is largely unknown. We analyzed cholesterol metabolism and estrogen biosynthesis condition of EMs lesions by biological information analysis of GEO datasets, and further verified both in vitro and in vivo by constructing EMs models with uterus fragments from donors of PRNP knockout mouse (Prnp-/-, KO119), Octapeptide repeat region of PRNP knockout mouse (KO120) and PRNP transgenic mouse (Tg20). We found that transcriptome of cholesterol metabolism and estrogen-converting enzymes were disturbed in EMs patients, and cellular cholesterol concentration and local estradiol level were substantially increased in EMs lesions, as well as the high level of prion (PrPC, encoded by PRNP). Notably, 17-ß estradiol stimulation significantly up-regulated PrPC expression in endometrial stromal cells (ESC) and PrPC promoted the proliferative, migratory and invasive abilities of ESC, and was further verified to accelerate EMs progression in mouse models. More importantly, PrPC promoted cholesterol accumulation and activated estrogen biosynthesis of ESC in a PPARα pathway-dependent manner. Taken together, this study suggests that PrPC-cholesterol metabolism/estrogen biosynthesis contributes to the progression of EMs by negatively regulating PPARα pathway, and could be potential therapeutic targets for EMs intervention.

A family cluster of infections by a newly recognized bunyavirus in eastern China, 2007: further evidence of person-to-person transmission.

BACKGROUND: Seven persons in one family living in eastern China developed fever and thrombocytopenia during May 2007, but the initial investigation failed to identify an infectious etiology. In December 2009, a novel bunyavirus (designated severe fever with thrombocytopenia syndrome bunyavirus [SFTSV]) was identified as the cause of illness in patients with similar clinical manifestations in China. We reexamined this family cluster for SFTSV infection. METHODS: We analyzed epidemiological and clinical data for the index patient and 6 secondary patients. We tested stored blood specimens from the 6 secondary patients using real time reverse transcription polymerase chain reaction (RT-PCR), viral culture, genetic sequencing, micro-neutralization assay (MNA), and indirect immunofluorescence assay (IFA). RESULTS: An 80-year-old woman with fever, leucopenia, and thrombocytopenia died on 27 April 2007. Between 3 and 7 May 2007, another 6 patients from her family were admitted to a local county hospital with fever and other similar symptoms. Serum specimens collected in 2007 from these 6 patients were positive for SFTS viral RNA through RT-PCR and for antibody to SFTSV through MNA and IFA. SFTSV was isolated from 1 preserved serum specimen. The only shared characteristic between secondary patients was personal contact with the index patient; none reported exposure to suspected animals or vectors. CONCLUSIONS: Clinical and laboratory evidence confirmed that the patients of fever and thrombocytopenia occurring in a family cluster in eastern China in 2007 were caused by a newly recognized bunyavirus, SFTSV. Epidemiological investigation strongly suggests that infection of secondary patients was transmitted to family members by personal contact.

ß-asarone suppresses HCT116 colon cancer cell proliferation and liver metastasis in part by activating the innate immune system.

Studies have revealed that ß-asarone exerts a powerful inhibitory effect on the proliferation of human cancer cells. The authors' previous study demonstrated that ß-asarone could induce LoVo colon cancer cell apoptosis in vitro and in vivo, indicating its anticancer properties. The present study aimed to determine the antineoplastic effect of ß-asarone in HCT116 colon cancer cells. An in vitro proliferation assay using a real time cell analyzer demonstrated that ß-asarone effectively decreased HCT116 cell proliferation in a dose-dependent manner. Bioinformatics analysis revealed that differentially expressed genes following ß-asarone inhibition were involved in the 'cell cycle', 'cell division', 'cell proliferation' and 'apoptosis'. Subsequently, a xenograft assay evidenced the inhibitory effect of ß-asarone on the growth of HCT116 tumors in vivo. Further detection of immune-associated cytokines and cells suggested that ß-asarone might be involved in the antitumor immune response by stimulating granulocyte-colony stimulating factor and increasing the number of macrophage cells in the spleen. Additionally, a murine model of splenic-transplantation verified the strong suppressive role of ß-asarone in colon cancer liver metastasis in vivo. Taken together, the results of the current study revealed that ß-asarone decreased HCT116 colon cancer cell proliferation and liver metastasis potentially by activating the innate immune system, supporting the multi-system regulation theory and providing a basis for further mechanistic studies on colon cancer.

Synthesis and photophysical studies of chiral helical macrocyclic scaffolds via coordination-driven self-assembly of 1,8,9,16-tetraethynyltetraphenylene. formation of monometallic platinum(II) and dimetallic platinum(II)-ruthenium(II) complexes.

This paper is concerned with the synthesis and reactions of enantiopure 1,8,9,16-tetraethynyltetraphenylene (3). We obtained 3 in 34% yield through four steps starting from 1,8,9,16-tetrahydroxytetraphenylene (2a) via a functional group interconversion strategy. On the basis of this chiral "helical" building block, three rigid helical macrocycles 14, 15, and 22 were designed. Complexes 14 and 15 were constructed via coordination-driven self-assembly with platinum(II) complexes 8 and 9b, while 22 cannot be obtained successfully. Then macrocycle 28 was designed on the structural basis of 22 to which octyl chains were introduced, in the hope of improving the solubility of the complex. Macrocycle 28 was finally formed and was characterized by NMR spectroscopy, elemental analysis, and electrospray mass spectrometry. For the enantiopure 15 and 28, circular dichroism (CD) spectra also exhibited chiral properties. Complexes 27 and 28 both exhibited an intense emission band at 621 nm in acetonitrile at 298 K upon excitation at λ > 420 nm.

Downregulated ABHD5 Aggravates Insulin Resistance of Trophoblast Cells During Gestational Diabetes Mellitus.

Lipid metabolism-associated molecule abhydrolase domain containing 5 (ABHD5) has been reported to have a role in insulin-mediated glucose uptake, the deregulation of it is associated with gestational diabetes mellitus (GDM). However, whether ABHD5 participates in glucose metabolism disorders in GDM patients has remained elusive. The present study aimed to clarify the role of ABHD5 in regulating insulin signaling in placentae during GDM. Reverse transcription-quantitative polymerase chain reaction (qRT-PCR) analysis was used for detecting the levels of ABHD5 and AMP kinase (AMPK), the insulin signaling molecules insulin receptor (INSR), INSR substrate (IRS1, IRS2), phosphoinositide 3-kinase (PI3K) and AKT, as well as the glucose transporter type 4 (GLUT-4) in placentae and the trophoblast cell line HTR-8/SVneo, while the protein level of ABHD5 was determined by western blotting. Pearson correlation analysis was performed to assess the correlation between the levels of ABHD5 and AMPK in placentae. In addition, ABHD5 overexpression in HTR-8/SVneo cells was achieved using plasmid vectors. The results indicated that the expression of ABHD5 and AMPK was dampened in placental tissues of females with GDM, and the levels of ABHD5 were positively correlated with AMPK. High-glucose (HG) treatment suppressed the expression of ABHD5, AMPK, GLUT-4, INSR, IRS, PI3K, and AKT in HTR-8/SVneo cells, and the overexpression of ABHD5 caused an elevation of the expression of these genes under normal and HG conditions in vitro. In conclusion, HG conditions induce insulin resistance of HTR-8/SVneo cells through downregulating ABHD5, which may account for impaired insulin signaling of placental tissues in GDM women.

Estrogen-regulated CD200 inhibits macrophage phagocytosis in endometriosis.

OBJECTIVES: Endometriosis (EMS) is a benign disease that is related to estrogen, immune disorders and inflammation. The purpose of this research was to determine the expression of CD200 in EMS and to clarify its role in the pathogenesis of the disease. METHODS: The levels of serum CD200 in patients with and without EMS were determined by ELISA. Furthermore, the expression of CD200 in normal eutopic endometrium and ectopic endometrium was detected by immunohistochemistry and western blotting. The CD200 receptor (CD200R) in macrophages in peritoneal fluid (pMØ) obtained from controls and patients with EMS was examined by western blotting. CD200 expression in human endometrial stromal cells (HESCs) stimulated with 17ß-estradiol (E2) was measured by western blotting. Furthermore, macrophages were stimulated with different concentrations of CD200 and the effect on phagocytosis was analyzed. RESULTS: The plasma CD200 levels of patients with EMS was significantly increased compared with controls (P = 0.0173, 95%CI [18.75, 159.6]). Compared with normal eutopic endometrium, the expression of CD200 was significantly increased in ectopic endometrial tissues. The CD200R expression in pMØ obtained from patients with EMS was increased compared with the controls (P = 0.0244). CD200 expression in HESCs stimulated with E2 was up-regulated. As the levels of CD200 increased, macrophage phagocytosis in vitro gradually decreased. CONCLUSIONS: CD200 is an estrogen-induced molecule that impairs macrophage phagocytosis and may contribute to the immune escape of ectopic lesions in EMS.

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study.

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

MiR-137 Restricts the Viability and Migration of HTR-8/SVneo Cells by Downregulating FNDC5 in Gestational Diabetes Mellitus.

BACKGROUND: An increasing number of studies have described the pathological changes of placenta tissues in gestational diabetes mellitus (GDM), although the underlying mechanisms involved in this process remain uncertain. The aim of the present study was to verify the possible role of microRNA-137 (miR)-137 and FNDC5 in regulating the biological function of trophoblasts in high glucose (HG) conditions during the GDM period. METHODS: Expression levels of miR-137 and FNDC5 were measured in placenta specimens, the HG-treated trophoblast cell line HTR-8/SVneo and miR-137- overexpressing HTR-8/SVneo cells using reverse transcription quantitative-PCR or western blotting. The viability of HTR-8/SVneo cells was tested using a Cell Counting kit- 8 (CCK8) assay, with cell migration assessed using scratch and transwell assays. RESULTS: It was observed that the expression levels of miR-137 were increased and the expression levels of FNDC5 were decreased in the placenta tissues of women with severe GDM and in HG-exposed HTR-8/SVneo cells. In addition, upregulating miR-137 in HTR-8/SVneo cells downregulated the expression levels of FNDC5. The viability and migration of HTR-8/SVneo cells were suppressed by increased miR-137 expression levels, and upregulating FNDC5 in miR-137-overexpressing HTR-8/SVneo cells resulted in the reversal of all these effects. CONCLUSIONS: The data from the present study suggest that miR-137 suppresses the viability and migration of trophoblasts via downregulating FNDC5 in GDM, which may contribute to the pathology of placenta tissues and occurrence of adverse pregnancy outcomes.

Chinese Patent medicine to treat a 32-year-old man with sinus bradycardia and cardiac sinus arrests: A case report.

RATIONALE: Sinus bradycardia refers to a sinus heart rate <60 bpm. Cardiac sinus arrests refer to the omission of atrial activation caused by transient cessation of impulse generation at the sinoatrial node. Normally, drugs such as atropine, isoproterenol, dopamine, dobutamine, or epinephrine can be used for the acute treatment of bradycardia. Temporary pacing is used for treating severe symptomatic bradycardia due to a reversible cause. Permanent cardiac pacing is used for chronic therapy of bradycardia. However, for traditional Chinese medicine (TCM), benefiting qi and nourishing yin and activating blood circulation is the general principle in treatment and show remarkable curative effects. PATIENT CONCERNS: A 32-year-old man was found to have 1-degree atrioventricular block and sinus bradycardia during a physical examination. He reported suffering from palpitation and shortness of breath occasionally. An ambulatory electrocardiogram showed sinus arrhythmia, sinus bradycardia, and significant sinus arrhythmia. The minimum heart rate was 33 bpm (beats per minute). The number of sinus arrest was 42 and the maximum RR interval was 2216 ms. DIAGNOSES: The patient was diagnosed with bradyarrhythmia in Western medicine and "palpitation" in TCM. INTERVENTIONS: The patient was treated with methods of benefiting qi and nourishing yin and activating blood circulation along with warming yan for nearly 5 months. CPM (Chinese patent medicine) such as Yixinshu capsule, Bingdouling oral liquid, Zhenyuan capsule, Zhibaidihuang pills were used for treatment. At the same time, he was suggested to change his lifestyles including falling asleep before 10:00 PM and abandoning spicy diets. OUTCOMES: The symptoms of palpitation and shortness of breath disappeared. The minimum heart rate increased from 33 to 42 bpm and sinus arrests did not occur. The maximum RR interval decreased from 2216 to 1650 ms and the remarkable sinus arrhythmia had improved obviously. LESSONS: This case report shows that TCM can be an effective alternative therapy for sinus bradycardia and cardiac sinus arrests. CPM may have been a successful intervention in arrhythmias.

Postischemic administration of Z-Ligustilide ameliorates cognitive dysfunction and brain damage induced by permanent forebrain ischemia in rats.

Previous studies have demonstrated that Z-Ligustilide (LIG), a characterized phthalide constituent present in numerous medical Umbelliferae plants, has significant neuroprotective effects in transient forebrain ischemia and permanent cerebral focal ischemia. The present study further investigated the effect of LIG on chronic cerebral hypoperfusion. Male Wistar rats were subjected to permanent ligation of both common carotid arteries (2VO). On Days 8-12 postsurgery, rat cognition was assessed in the Morris water maze. Rats with significantly impaired acquisition of spatial information were randomly allocated to three groups and orally administered LIG (10 or 40 mg/kg/day) or volume-matched vehicle on Days 13-40 post-2VO surgery. The sham-operated group served as controls. After long-term treatment with LIG, the impaired animals' behavioral, biochemical, and histopathological features were examined. Compared to the sham-operated group, significant cognitive impairment was observed in the vehicle-treated group 40 days after 2VO. Shortened mean escape latency was detected in the Morris water maze in rats treated with LIG (p<0.01 vs. vehicle-treated group) during the same trial days. Chronic 2VO-induced pathological changes included neuronal loss and an increase of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the hippocampus. These effects were prevented with LIG treatment (p<0.01 vs. vehicle-treated group). LIG also significantly reduced malondialdehyde levels and increased superoxide dismutase activity in ischemic brain tissue (p<0.05 and p<0.01 vs. vehicle-treated group). In addition, LIG significantly increased choline acetyltransferase activity and inhibited acetylcholinesterase activity in ischemic brain tissues (p<0.05 and p<0.01 vs. vehicle-treated group). The present data demonstrate that LIG significantly prevented chronically hypoperfused cognitive deficits and brain damage at least partly through an antioxidant effect and improved cholinergic activity. The present findings suggest that LIG may have therapeutic potential in treating vascular dementia and cerebrovascular insufficiency.