AIM: To study the preventive effects of Qianggan-Rongxian Decoction on liver fibrosis induced by dimethylnitrosamine (DMN) in rats.
METHODS: Male Wistar rats were randomly divided into hepatic fibrosis model group, control group and 3 treatment groups (12 rats in each group). Except for the normal control group, all the rats received 1% DMN (10 μL/kg body weight, i.p), 3 times a week for 4 wk. The rats in the 3 treatment groups including a high-dose DMN group (10 mL/kg), a medium-dose DMN group (7 mL/kg), and a low-dose DMN group (4 mL/kg) were daily gavaged with Qianggan-Rongxian Decoction, and the rats in the model and normal control groups were given saline vehicle. Enzyme-linked immunosorbent assay (ELISA) was used to determine the changes in serum hyaluronic acid (HA), laminin (LN), and type IV collagen levels. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using routine laboratory methods. Pathologic changes, particularly fibrosis, were examined by hematoxylin and eosin (HE) and Sirius red staining. Hepatic stellate cells (HSC) were examined by transmission electron microscopy.
RESULTS: Compared with the model control group, the serum levels of HA, LN, type IV collagen, ALT and AST were decreased markedly in the other groups after treatment with Qianggan-Rongxian Decoction, especially in the medium-dose DMN group (P < 0.05). Moreover, the area-density percentage of collagen fibrosis was lower in the Qianggan-Rongxian Decoction treatment groups than in the model group, and a more significant drop was observed in the medium-dose DMN group (P < 0.05).
CONCLUSION: Qianggan-Rongxian Decoction can inhibit hepatic fibrosis due to chronic liver injury, delay the development of cirrhosis, and notably ameliorate liver function. It may be used as a safe and effective thera-peutic drug for patients with fibrosis.
Liver fibrosis; Qianggan-Rongxian Decoction; Prevention; Rat model; Dimethylnitrosamine
Phosphodiesterases (PDEs) are critical regulatory enzymes in cyclic nucleotide signaling. PDEs have diverse expression patterns within the central nervous system (CNS), show differing affinities for cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), and regulate a vast array of behaviors. Here, we investigated the expression profile of the PDE8 gene family members Pde8a and Pde8b in the mouse brain. We find that Pde8a expression is largely absent in the CNS; by contrast, Pde8b is expressed in select regions of the hippocampus, ventral striatum, and cerebellum. Behavioral analysis of mice with Pde8b gene inactivation (PDE8B KO) demonstrate an enhancement in contextual fear, spatial memory, performance in an appetitive instrumental conditioning task, motor-coordination, and have an attenuation of age-induced motor coordination decline. In addition to improvements observed in select behaviors, we find basal anxiety levels to be increased in PDE8B KO mice. These findings indicate that selective antagonism of PDE8B may be an attractive target for enhancement of cognitive and motor functions; however, possible alterations in affective state will need to be weighed against potential therapeutic value.
Photothermal ablation (PTA) is an emerging technique that uses near-infrared laser light-generated heat to destroy tumor cells. However, complete tumor eradication by PTA therapy alone is difficult because heterogeneous heat distribution can lead to sub-lethal thermal dose in some areas of the tumor. Successful PTA therapy requires selective delivery of photothermal conducting nanoparticles to mediate effective PTA of tumor cells, and the ability to combine PTA with other therapy modalities. Here, we synthesized multifunctional doxorubicin (DOX)-loaded hollow gold nanospheres (DOX@HAuNS) that target EphB4, a member of the Eph family of receptor tyrosine kinases overexpressed on the cell membrane of multiple tumors and angiogenic blood vessels. Increased uptake of targeted nanoparticles T-DOX@HAuNS was observed in three EphB4-positive tumors both in vitro and in vivo. In vivo release of DOX from DOX@HAuNS, triggered by near-infrared laser, was confirmed by dual radiotracer technique. Treatment with T-DOX@HAuNS followed by near-infrared laser irradiation resulted in significantly decreased tumor growth when compared to treatments with non-targeted DOX@HAuNS plus laser or HAuNS plus laser. The tumors in six of the eight mice treated with T-DOX@HAuNS plus laser regressed completely with only residual scar tissue by 22 days following injection, and none of the treatment groups experienced a loss in body weight. Together, our findings demonstrate that concerted chemo-photothermal therapy with a single nanodevice capable of mediating simultaneous PTA and local drug release may have promise as a new anticancer therapy.
Hollow Gold Nanospheres; EphB4 receptors; Targeting; Doxorubicin; Multimodal Therapy
Our knowledge of the pathophysiology of affect dysregulation has progressively increased, but the pharmacological treatments remain inadequate. Here, we summarize the current literature on deficits in somatostatin, an inhibitory modulatory neuropeptide, in major depression and other neurological disorders that also include mood disturbances. We focus on direct evidence in the human postmortem brain, and review rodent genetic and pharmacological studies probing the role of the somatostatin system in relation to mood. We also briefly go over pharmacological developments targeting the somatostatin system in peripheral organs and discuss the challenges of targeting the brain somatostatin system. Finally, the fact that somatostatin deficits are frequently observed across neurological disorders suggests a selective cellular vulnerability of somatostatin-expressing neurons. Potential cell intrinsic factors mediating those changes are discussed, including nitric oxide induced oxidative stress, mitochondrial dysfunction, high inflammatory response, high demand for neurotrophic environment, and overall aging processes. Together, based on the co-localization of somatostatin with gamma-aminobutyric acid (GABA), its presence in dendritic-targeting GABA neuron subtypes, and its temporal-specific function, we discuss the possibility that deficits in somatostatin play a central role in cortical local inhibitory circuit deficits leading to abnormal corticolimbic network activity and clinical mood symptoms across neurological disorders.
somatostatin; somatostatin-expressing interneurons; SST; SOM; SRIF; depression; mood disorders; GABA inhibition
This study investigated the propagated sensation along meridians (PSM) produced respectively by acupuncture at a specific acupoint of right-side Quchi (LI11), a nonacupoint on meridian (control meridian point), and neither meridian nor acupoint (control point). All the stimulated points were on the right brachioradialis along the large intestine meridian of hand Yangming. Surface electromyography (sEMG) was used to reflect the activity of the brachioradialis along the large intestine meridian of hand Yangming. The PSM rate of LI11 (59.21%) and the control meridian point (53.95%) were significantly higher than the control point (38.16%) (P < 0.05). After acupuncture, the brachioradialis sEMG amplitude was 5.08 ± 2.93 uV at LI11, 3.08 ± 1.18 uV at the control point, and 2.77 ± 1.36 uV at the control meridian point. The amplitude of LI11 was significantly higher than both the control meridian point and the control point (P < 0.05). When the sEMG activity of brachioradialis returned to the stable base line, brachioradialis sEMG duration at LI11 (265 ± 87.87 s) was significantly longer than that at the control meridian point (91.69 ± 42.98 s) and the control point (83.31 ± 32.76 s) (P < 0.05). In conclusion, acupuncture activated PSM at all points but showed an acupoint specificity at LI11 and a meridian specificity at the control meridian point.
Photoacoustic tomography (PAT) is an emerging molecular imaging modality. Here, we demonstrate use of semiconductor copper sulfide nanoparticles (CuS NP) for PAT with an Nd:YAG laser at a wavelength of 1064 nm. CuS NP allowed visualization of mouse brain after intracranial injection, rat lymph nodes 12 mm below the skin after interstitial injection, and CuS NP-containing agarose gel embedded in chicken breast muscle at the depth of ~ 5 cm. This imaging approach has great potential for molecular imaging of breast cancer.
photoacoustic tomography; CuS nanoparticles; 1064-nm laser; optical imaging
We report the electronic recording of the touch contact and pressure using an active matrix pressure sensor array made of transparent zinc oxide thin-film transistors and tactile feedback display using an array of diaphragm actuators made of an interpenetrating polymer elastomer network. Digital replay, editing and manipulation of the recorded touch events were demonstrated with both spatial and temporal resolutions. Analog reproduction of the force is also shown possible using the polymer actuators, despite of the high driving voltage. The ability to record, store, edit, and replay touch information adds an additional dimension to digital technologies and extends the capabilities of modern information exchange with the potential to revolutionize physical learning, social networking, e-commerce, robotics, gaming, medical and military applications.
Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depression. Individuals with type 2 diabetes (T2DM) have a high prevalence of major depression and low levels of BDNF. We therefore explored whether the BDNF Val66Met polymorphism is associated with co-morbid depression and whether depression affects the serum levels of BDNF in a Han Chinese subjects with T2DM.
A Total of 296 T2DM patients and 70 healthy volunteers (Health control, HC group) were recruited in this study. T2DM patients were divided into two subgroups: depressive diabetes group (DDM group, n = 64) and non-depressive diabetes group (NDDM group, n = 232), according to the presence or the absence of depression assessed by Center for Epidemiologic Studies Depression Scale (CES-D) and Patient Health Questionnaire-9 (PHQ-9). Val66Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). Serum BDNF levels were measured by ELISA kit.
In this study, 21.6% (64/296) patients with T2DM had depression. The BDNF Val66Met genotype distributions were statistically different among the three groups (χ2 = 7.39, p < 0.05). DDM group carried the highest frequencies of Met allele (53.9%) compared to HC group (39.3%) and NDDM group (38.8%). Subjects with Met/Met had lowest serum BDNF levels (76.59 ± 5.12 pg/ml, F = 7.39, p < 0.05) compared to subjects with Val/Met (79.04 ± 5.19 pg/ml) and Val/Val (83.83 ± 3.97 pg/ml). Within T2DM group, it was also observed that the serum BDNF levels in DDM group were significantly lower than those in NDDM group (76.67 ± 5.35 vs. 79.84 ± 3.97 pg/ml, p < 0.05). In type 2 diabetes subjects, BDNF serum levels were significant correlations with genotypes (r = −0.346, p < 0.01), depression scores (r = −0.486, p < 0.01) and HbA1c (r = −0.168, p < 0.05). After adjustment for gender, HbA1c, BMI and numbers of complications, BDNF Val/Met genotype distributions (OR = 2.105, p < 0.05) and decreased serum BDNF levels (OR = 0.835, p < 0.01) were independently associated with depression in T2DM.
The BDNF Val66Met polymorphism might be implicated in the pathogenesis of depression in T2DM by decreasing serum BDNF levels in Han Chinese Subjects.
Type 2 diabetes (T2DM); Depression; Brain-derived neurotrophic factor (BDNF); Polymorphism
Hyperplasia of synovial fibroblasts, infiltration with inflammatory cytokines, and tissue hypoxia are the major characteristics of rheumatoid arthritis (RA). Interleukin 33 (IL-33) is a newly identified inflammatory cytokine exacerbating the disease severity of RA. Hypoxia-inducible factor-1α (HIF-1α) showed increased expression in RA synovium and could regulate a number of inflammatory cytokine productions. Nevertheless, its correlation with IL-33 remains largely unknown. Here, we showed that elevated levels of IL-33 were demonstrated in RA patient synovial fluids, with upregulated expression of HIF-1α and IL-33 in the synovial fibroblasts. Knocking down HIF-1α compromised IL-33 expression in rheumatoid arthritis synovial fibroblasts (RASF), while enforcing HIF-1α expression in RASF substantially upregulated IL-33 levels. HIF-1α promoted the activation of the signalling pathways controlling IL-33 production, particularly the p38 and ERK pathways. Moreover, we showed for the first time that IL-33 in turn could induce more HIF-1α expression in RASF, thus forming a HIF-1α/IL-33 regulatory circuit that would perpetuate the inflammatory process in RA. Targeting this pathological pathway and HIF-1α may provide new therapeutic strategies for overcoming the persistent and chronic inflammatory disease.
Targeted nanoparticle-based delivery systems have been used extensively to develop effective cancer theranostics. However, how targeting ligands affect extravascular transport of nanoparticles in solid tumors remains unclear. Here, we show, using B16/F10 melanoma cells expressing melanocortin type-1 receptor (MC1R), that the nature of targeting ligands, i.e., whether they are agonists or antagonists, directs tumor uptake and intratumoral distribution after extravasation of nanoparticles from tumor vessels into the extravascular fluid space. Pegylated hollow gold nanospheres (HAuNS, diameter≈40 nm) coated with MC1R agonist are internalized upon ligand-receptor binding, whereas MC1R antagonist-conjugated HAuNS remain attached on the cell surface. Transcellular transport of agonist-conjugated HAuNS was confirmed by a multilayer tumor cell model and by transmission electron microscopy. MC1R agonist- but not MC1R antagonist-conjugated nanoparticles exhibit significantly higher tumor uptake than nontargeted HAuNS and are quickly dispersed from tumor vessels via receptor-mediated endocytosis and subsequent transcytosis. These results confirm an active transport mechanism that can be used to overcome one of the major biological barriers for efficient nanoparticle delivery to solid tumors.
Nanoparticles; Melanocortin type-1 receptor (MC1R); Transcytosis; Agonists; Antagonists
Sequencing studies using whole-genome or exome scans are still more expensive than genome wide association studies (GWAS) on a per-subject basis. As a result, subsets of subjects from a larger study are often selected for sequencing. To perform an agnostic investigation of the entire genome, subjects may be selected that capture independent ancestral lineages, i.e. founder genomes, and thus avoid redundant information from regions that were inherited identical by descent (IBD) from a common ancestor. We present SampleSeq2 which can be used to select a subset of optimally unrelated subjects with minimal IBD sharing. It also can be used to estimate the number, GT, of founder chromosomes in a sample or select the minimum number of subjects that will carry a target GT. We evaluated SampleSeq2 compared to a random draw of a small number of subjects both by simulation and using the Anabaptist genealogy. SampleSeq2 provided an increase in GT relative to a random draw across a range of small sample sizes. This increase in founder chromosomes improves the power of association tests, mitigates the effect of cryptic relatedness on parameter estimates, increases the total yield of alleles from sequencing, and minimizes the average size of regions shared IBD around disease alleles in cases.
resequencing; ancestry; cryptic relatedness; study design; subject selection
Objective. The aim of the study was to assess adrenomedullin (AM) as a predictor for development of severe sepsis and septic shock in emergency department (ED). Method. From December 2011 to October 2012, 372 consecutive septic patients admitted to ED were enrolled. AM was examined in every patient. All patients were followed up for 3 days. The outcome variable was development of severe sepsis or septic shock. The predictive ability of AM was evaluated by binary logistic regression analysis and receiver operating characteristic (ROC) curve. Result. On admission, the differences of AM among patients with different comorbidities, infections, and culture results were not significant. AM level was higher in patients who progressed than in who did not (41.63 ± 6.55 versus 31.31 ± 7.71 ng/L, P < 0.001). AM was the only independent predictor of outcome. The area under ROC curve of AM was 0.847. With a cutoff value of 41.24 ng/L, the sensitivity was 67.6%, the specificity was 90.0%, the positive predictive value was 61.5%, the negative predictive value was 92.2%, the positive likelihood ratio was 6.78, and the negative likelihood ratio was 0.36. Conclusion. Adrenomedullin is valuable for predicting development of severe sepsis and septic shock in ED.
To achieve an easily established, safe, and reproducible animal model for the study of heterotopic bone formation around vessels, a small animal series using New Zealand White rabbits was performed. Three different dosages of recombinant human bone morphogenic protein (rhBMP-2) carried by fibrin matrix were tested. A guided tissue regeneration (GTR) membrane sheet was formed into a tube and allowed to harden; it served both to maintain the space around the vessel bundle and to separate the fibrin matrix with rhBMP-2 from skeletal muscle. Wrapped around the femoral vessel bundle and fixed in place, the tube was filled with the fibrin matrix containing rhBMP-2. The surgical site was closed in layers, and the postoperative healing was uneventful. All animals resumed their full preoperative daily activities 3–4 days after the operation. No adverse events such as wound dehiscence or infection occurred, and all animals could be sacrified at the scheduled date. Micro–computed tomography and histological investigations showed heterotopic bone formation around the vessel bundle in the medium- and high-dosage rhBMP-2 groups. An easy, safe, and reproducible animal model that allows the study of heterotopic bone formation around vessels was successfully established.
biomaterials; growth factor; tissue engineering
Slight elevations in cardiac troponin I and T are frequently observed after percutaneous coronary intervention (PCI). Contrast-induced acute kidney injury (CI-AKI) is a complex syndrome induced by exposure to intravascular contrast media (CM). Currently, the relationships between the CM, pre-existing kidney insufficiency, CI-AKI, and myonecrosis after elective PCI are unclear. To investigate the relationship between CI-AKI and post-procedural myonecrosis (PMN) after PCI, we analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. The levels of cardiac troponins (cTns), cTnI and cTnT, at baseline and on at least one occasion 18–24 h after PCI were measured. We also recorded serum levels of creatinine (SCr) and the urine albumin:creatinine ratio (ACR) before coronary angiography, and 24–48 h and 48–72 h after contrast administration. A post-procedure increase in cTns was detected in 16.21% (53/327) of subjects with cTns levels >99th to 5×99th percentile upper reference limit (URL). Twenty-seven patients (8.26%) developed CI-AKI. CI-AKI occurred more often in subjects with PMN than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Multiple logistic regression analysis revealed that pre-existing microalbuminuria (MA) was an important independent predictor of PMN (OR: 3.31; 95% CI: 1.26–8.65, P=0.01). However, there was no correlation between the incidence of CI-AKI and PMN (OR: 2.38; 95% CI: 0.88–6.46, P=0.09). We conclude that pre-existing MA was not only an important independent predictor of CI-AKI but also of PMN.
Percutaneous coronary intervention; Myonecrosis; Contrast-induced nephropathy; Acute kidney injury; Contrast media
Cryptococcosis presenting as endobronchial obstruction was scarce. We report a case of patient with cryptococcosis. A chest CT scan showed masses in the right upper lobe and right hilar, with evidence of narrowing of the right upper lobe bronchus. PET-CT scans showed the mass in the bronchus with the high mSUVs. A biopsy specimen was taken from the mass by lung puncture biopsy and showed cryptococcus infection. Culture of lung tissue was C. neoformans. The serum was positive for cryptococcal antigen, with a titer of more than 1:1,280. He was successfully treated using amphotericin B liposome. This case is worth discussing because it was cryptococcosis presenting as endobronchial obstruction that is often considered tumor.
Cryptococcosis; airway obstruction; amphotericin B liposome
Five new anthranilic acid derivatives, penipacids A–E (1–5), together with one known analogue (6), which was previously synthesized, were characterized from the ethyl acetate extract of the marine sediment-derived fungus Penicillium paneum SD-44. Their structures were elucidated mainly by extensive NMR spectroscopic and mass spectrometric analysis. The cytotoxicity and antimicrobial activity of the isolated compounds were evaluated. Compounds 1, and 5 exhibited inhibitory activity against human colon cancer RKO cell line, while compound 6 displayed cytotoxic activity against Hela cell line.
marine fungus; sediment; anthranilic acid; Penicillium paneum; cytotoxicity
Graphene has a unique atom-thick two-dimensional structure and excellent properties, making it attractive for a variety of electrochemical applications, including electrosynthesis, electrochemical sensors or electrocatalysis, and energy conversion and storage. However, the electrochemistry of single-layer graphene has not yet been well understood, possibly due to the technical difficulties in handling individual graphene sheet. Here, we report the electrochemical behavior at single-layer graphene-based electrodes, comparing the basal plane of graphene to its edge. The graphene edge showed 4 orders of magnitude higher specific capacitance, much faster electron transfer rate and stronger electrocatalytic activity than those of graphene basal plane. A convergent diffusion effect was observed at the sub-nanometer thick graphene edge-electrode to accelerate the electrochemical reactions. Coupling with the high conductivity of a high-quality graphene basal plane, graphene edge is an ideal electrode for electrocatalysis and for the storage of capacitive charges.
The effect of rescue breathing on neurologic prognosis after cardiopulmonary resuscitation (CPR) is controversial. Therefore, we investigated the cerebral microcirculatory and oxygen metabolism during continuous compression (CC) and 30:2 CPR (VC) in a porcine model of cardiac arrest to determine which is better for neurologic prognosis after CPR.
After 4 min of ventricular fibrillation, 20 pigs were randomised into two groups (n=10/group) receiving CC-CPR or VC-CPR. Cerebral oxygen metabolism and blood flow were measured continuously using laser Doppler flowmetry. Haemodynamic data were recorded at baseline and 5 min, 30 min, 2 h and 4 h after restoration of spontaneous circulation (ROSC).
Compared with the VC group, the mean cortical cerebral blood flow was significantly higher at 5 min ROSC in the CC group (P<0.05), but the difference disappeared after that time point. Brain percutaneous oxygen partial pressures were higher, and brain percutaneous carbon dioxide partial pressures were lower, in the VC group from 30 min to 4 h after ROSC; significant differences were found between the two groups (P<0.05). However, no significant difference of the cerebral oxygen extraction fraction existed between the two groups.
Inconsistency of systemic circulation and cerebral microcirculation with regard to blood perfusion and oxygen metabolism is common after CPR. No significant differences in cortical blood flow and oxygen metabolism were found between the CC-CPR and VC-CPR groups after ROSC.
Brain ischemia; Microcirculation; Cardiopulmonary resuscitation; Laser Doppler flowmetry; Haemodynamics
High-grade primary brain tumors possessed poor outcome due to invasiveness. Extracellular matrix metalloproteinase inducer (EMMPRIN) stimulates peri-tumoral fibroblasts to secrete matrix metalloproteinase and promote invasiveness. This study hypothesized that high-grade brain tumors overexpress EMMPRIN. Analyzing the public delinked database from the Gene Expression Omnibus profile, the results showed that the EMMPRIN mRNA level was higher in WHO grade IV (n = 81) than in grade III (n = 19, p < 0.0005) astrocytomas and non-tumor brain tissue controls (n = 23, p < 0.00001). The results of tissue microarray-based immunohistochemical (IHC) staining revealed that EMMPRIN levels positively correlated with WHO grades for astrocytomas (p = 0.008) and meningiomas (p = 0.048). EMMPRIN mRNA levels in conventional glioma cell lines (n = 36) was not less than those in glioma primary culture cells (n = 27) and glioblastoma stem-like cells (n = 12). The GBM8401, U87MG, and LN229 human glioma cell lines also overexpressed EMMPRIN. Hematoxylin and eosin, IHC, and immunofluorescence staining of xenografts confirmed that high-grade brain tumors overexpressed EMMPRIN. Lastly, Kaplan–Meier analysis revealed poorer survival in WHO grade IV (n = 56) than in grade III astrocytomas (n = 21, by log-rank test; p = 0.0001, 95 % CI: 1.842–3.053). However, in high-grade astrocytomas, there was no difference in survival between high and low EMMPRIN mRNA levels. Thus, this study identified that high-grade brain tumors overexpress EMMPRIN, which positively correlates with WHO grades in human astrocytomas and meningiomas, and suggests that EMMPRIN may be a therapeutic target of brain tumor.
Astrocytoma; Meningioma; EMMPRIN; GEO profile; WHO grades; Tumor stem-like cells
Although polymeric magnetic resonance imaging (MRI) agents have significantly improved relaxivity and prolonged circulation time in vivo compared with current imaging agents, the potential for long-term toxicity prevents their translation into the clinic. The aim of this study was to develop a new biodegradable, nonionic polymeric blood pool MRI contrast agent with efficient clearance from the body. We synthesized PHPG-DTPA, which possesses two potentially degradable sites in vivo: protein amide bonds of the polymer backbone susceptible to enzymatic degradation and hydrolytically labile ester bonds in the side chains. After chelation with Gd3+, PHPG-DTPA-Gd displayed an R1 relaxivity of 15.72 mM−1 · sec −1 (3.7 times higher than that of MagnevistT). In vitro, DTPA was completely released from PHPG polymer within 48 h when incubated in mouse plasma. In vivo, PHPG-DTPA-Gd was cleared via renal route as shown by micro-single photon computed tomography of mice after intravenous injection of 111In-labeled PHPG-DTPA-Gd. MRI of nude rats bearing C6 glioblastoma showed significant enhancement of the tumor periphery after intravenous injection of PHPG-DTPA-Gd. Furthermore, mouse brain angiography was clearly delineated up to 2 h after injection of PHPG-DTPA-Gd. PHPG-DTPA-Gd’s biodegradability, efficient clearance, and significantly increased relaxivity make it a promising polymeric blood pool MRI contrast agent.
Four new quinazolinone alkaloids, namely, aniquinazolines A–D (1–4), were isolated and identified from the culture of Aspergillus nidulans MA-143, an endophytic fungus obtained from the leaves of marine mangrove plant Rhizophora stylosa. The structures of the new compounds were elucidated by spectroscopic analysis, and their absolute configurations were determined on the basis of chiral HPLC analysis of the acidic hydrolysates. The structure for 1 was confirmed by single-crystal X-ray diffraction analysis. All these compounds were examined for antibacterial and cytotoxic activity as well as brine shrimp (Artemia salina) lethality.
mangrove; endophytic fungus; Aspergillus nidulans; secondary metabolites; bioactivity
Recent evidence suggests that chloride (CL−) channels are involved in myocardial ischemia. In this study, the impact of acupuncture on the protein expressions of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and CLC-2 CL− channel of the rats with myocardial ischemia were tested and its mechanism was explored. The rats for experiment were distributed randomly into 5 groups: blank control group, modeling control group, Neiguan (PC-6) treatment group, Lieque (LU-7) control group, and Non-acupoint control group. The rats of all groups, except the blank control group, had myocardial ischemia via multiple subcutaneous injection of isoproterenol (ISO). Electroacupuncture treatment was given to Neiguan (PC-6) treatment group, Lieque (LU-7) control group, and Non-acupoints control group, respectively, once a day for 7 days. The results show that acupuncture can alleviate the myocardial ischemia of cardiac tissue, decrease significantly the activities of serum SOD and MDA, and thereby influence the protein expressions of CFTR and CLC-2 in CL− channels. The results of the study implies that acupuncture suppresses the pathological changes of cardiac tissue of rats with myocardial ischemia and regulates the protein expression of CFTR and CLC-2 CL− channels, which may serve as one possible mechanism to reduce myocardial ischemia.
Stem cells are essential for the regeneration and homeostasis of many organs, such as tooth, hair, skin, and intestine. Although human tooth regeneration is limited, a number of animals have evolved continuously growing teeth that provide models of stem cell-based organ renewal. A well-studied model is the mouse incisor, which contains dental epithelial stem cells in structures known as cervical loops. These stem cells produce progeny that proliferate and migrate along the proximo-distal axis of the incisor and differentiate into enamel-forming ameloblasts. Here, we studied the role of E-cadherin in behavior of the stem cells and their progeny. Levels of E-cadherin are highly dynamic in the incisor, such that E-cadherin is expressed in the stem cells, downregulated in the transit-amplifying cells, re-expressed in the pre-ameloblasts and then downregulated again in the ameloblasts. Conditional inactivation of E-cadherin in the cervical loop led to decreased numbers of label-retaining stem cells, increased proliferation, and decreased cell migration in the mouse incisor. Using both genetic and pharmacological approaches, we showed that Fibroblast Growth Factors regulate E-cadherin expression, cell proliferation and migration in the incisor. Together, our data indicate that E-cadherin is an important regulator of stem cells and their progeny during growth of the mouse incisor.
E-cadherin; Epithelial stem cells; Cell migration; Cell proliferation; Incisor; Ameloblasts; Fibroblast Growth factors (FGFs); Sprouty genes; Mouse
The aim of this study was to evaluate the effect of mild hypothermia on the coagulation-fibrinolysis system and physiological anticoagulants after cardiopulmonary resuscitation (CPR). A total of 20 male Wuzhishan miniature pigs underwent 8 min of untreated ventricular fibrillation and CPR. Of these, 16 were successfully resuscitated and were randomized into the mild hypothermia group (MH, n = 8) or the control normothermia group (CN, n = 8). Mild hypothermia (33°C) was induced intravascularly, and this temperature was maintained for 12 h before pigs were actively rewarmed. The CN group received normothermic post-cardiac arrest (CA) care for 72 h. Four animals were in the sham operation group (SO). Blood samples were taken at baseline, and 0.5, 6, 12, 24, and 72 h after ROSC. Whole-body mild hypothermia impaired blood coagulation during cooling, but attenuated blood coagulation impairment at 72 h after ROSC. Mild hypothermia also increased serum levels of physiological anticoagulants, such as PRO C and AT-III during cooling and after rewarming, decreased EPCR and TFPI levels during cooling but not after rewarming, and inhibited fibrinolysis and platelet activation during cooling and after rewarming. Finally, mild hypothermia did not affect coagulation-fibrinolysis, physiological anticoagulants, or platelet activation during rewarming. Thus, our findings indicate that mild hypothermia exerted an anticoagulant effect during cooling, which may have inhibitory effects on microthrombus formation. Furthermore, mild hypothermia inhibited fibrinolysis and platelet activation during cooling and attenuated blood coagulation impairment after rewarming. Slow rewarming had no obvious adverse effects on blood coagulation.