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1.
BMC Cardiovasc Disord ; 19(1): 216, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31601179

RESUMO

BACKGROUND: Infantile hepatic hemangioma (IHH) is a rare endothelial cell neoplasm, which may be concurrent with severe complications and result in poor outcomes. Moreover, the coexistence of IHH and congenial heart disease is even rarer. CASE PRESENTATION: We present a 10-day-old male born with IHH associated with patent ductus arteriosus (PDA), atrial septal defect (ASD) and pulmonary hypertension. Moreover, we reviewed a series of studies of IHH-associated high-output cardiac failure between 1974 and 2018, and summarized the treatment outcomes. CONCLUSIONS: Infantile hepatic hemangioma (IHH) has been known to induce high-output heart failure. There is no literature to summarize the severity of its impact on heart, which can lead to a high mortality rate. When IHH is detected by ultrasound, the heart should be evaluated to facilitate treatment. The outcomes of IHH associated with heart failure are good.

2.
Arterioscler Thromb Vasc Biol ; : ATVBAHA119313253, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31578081

RESUMO

OBJECTIVE: HDL (high-density lipoprotein) infusion reduces atherosclerosis in animal models and is being evaluated as a treatment in humans. Studies have shown either anti- or proinflammatory effects of HDL in macrophages, and there is no consensus on the underlying mechanisms. Here, we interrogate the effects of HDL on inflammatory gene expression in macrophages. Approach and Results: We cultured bone marrow-derived macrophages, treated them with reconstituted HDL or HDL isolated from APOA1Tg;Ldlr-/- mice, and challenged them with lipopolysaccharide. Transcriptional profiling showed that HDL exerts a broad anti-inflammatory effect on lipopolysaccharide-induced genes and proinflammatory effect in a subset of genes enriched for chemokines. Cholesterol removal by 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine liposomes or ß-methylcyclodextrin mimicked both pro- and anti-inflammatory effects of HDL, whereas cholesterol loading by 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine/cholesterol-liposomes or acetylated LDL (low-density lipoprotein) before HDL attenuated these effects, indicating that these responses are mediated by cholesterol efflux. While early anti-inflammatory effects reflect reduced TLR (Toll-like receptor) 4 levels, late anti-inflammatory effects are due to reduced IFN (interferon) receptor signaling. Proinflammatory effects occur late and represent a modified ER stress response, mediated by IRE1a (inositol-requiring enzyme 1a)/ASK1 (apoptosis signal-regulating kinase 1)/p38 MAPK (p38 mitogen-activated protein kinase) signaling, that occurs under conditions of extreme cholesterol depletion. To investigate the effects of HDL on inflammatory gene expression in myeloid cells in atherosclerotic lesions, we injected reconstituted HDL into Apoe-/- or Ldlr-/- mice fed a Western-type diet. Reconstituted HDL infusions produced anti-inflammatory effects in lesion macrophages without any evidence of proinflammatory effects. CONCLUSIONS: Reconstituted HDL infusions in hypercholesterolemic atherosclerotic mice produced anti-inflammatory effects in lesion macrophages suggesting a beneficial therapeutic effect of HDL in vivo.

3.
JMIR Mhealth Uhealth ; 7(10): e14120, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31579026

RESUMO

BACKGROUND: Wrist-worn activity trackers are popular, and an increasing number of these devices are equipped with heart rate (HR) measurement capabilities. However, the validity of HR data obtained from such trackers has not been thoroughly assessed outside the laboratory setting. OBJECTIVE: This study aimed to investigate the validity of HR measures of a high-cost consumer-based tracker (Polar A370) and a low-cost tracker (Tempo HR) in the laboratory and free-living settings. METHODS: Participants underwent a laboratory-based cycling protocol while wearing the two trackers and the chest-strapped Polar H10, which acted as criterion. Participants also wore the devices throughout the waking hours of the following day during which they were required to conduct at least one 10-min bout of moderate-to-vigorous physical activity (MVPA) to ensure variability in the HR signal. We extracted 10-second values from all devices and time-matched HR data from the trackers with those from the Polar H10. We calculated intraclass correlation coefficients (ICCs), mean absolute errors, and mean absolute percentage errors (MAPEs) between the criterion and the trackers. We constructed decile plots that compared HR data from Tempo HR and Polar A370 with criterion measures across intensity deciles. We investigated how many HR data points within the MVPA zone (≥64% of maximum HR) were detected by the trackers. RESULTS: Of the 57 people screened, 55 joined the study (mean age 30.5 [SD 9.8] years). Tempo HR showed moderate agreement and large errors (laboratory: ICC 0.51 and MAPE 13.00%; free-living: ICC 0.71 and MAPE 10.20%). Polar A370 showed moderate-to-strong agreement and small errors (laboratory: ICC 0.73 and MAPE 6.40%; free-living: ICC 0.83 and MAPE 7.10%). Decile plots indicated increasing differences between Tempo HR and the criterion as HRs increased. Such trend was less pronounced when considering the Polar A370 HR data. Tempo HR identified 62.13% (1872/3013) and 54.27% (5717/10,535) of all MVPA time points in the laboratory phase and free-living phase, respectively. Polar A370 detected 81.09% (2273/2803) and 83.55% (9323/11,158) of all MVPA time points in the laboratory phase and free-living phase, respectively. CONCLUSIONS: HR data from the examined wrist-worn trackers were reasonably accurate in both the settings, with the Polar A370 showing stronger agreement with the Polar H10 and smaller errors. Inaccuracies increased with increasing HRs; this was pronounced for Tempo HR.

4.
J Pharm Biomed Anal ; 177: 112732, 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31568965

RESUMO

Dingkun Dan (DKD) has been widely used for a variety of gynecological disease. However, the systematic analysis of the chemical constituents of DKD has not been well established because of the complexity of the formula and confidentiality. In this paper, liquid chromatography Q Exactive high resolution accurate mass spectrometry (UHPLC-QE-HRMS) with automated MetaboLynx analysis was established to characterize the chemical constituents of DKD. The analysis was performed on a Water Acquity UPLC® HSS T3 using a gradient elution system. Full scan ranged 100-1500 m/z in positive and negative ion mode combined with MS/MS fragmentation for top 5 ions was proposed for aiding the structural identification of the components. All of the peaks were tentatively characterized by not only comparing the retention time and MS data with those from reported literature and database, but also summarizing the fragmentation pathways and promoting to other ingredients identification. Additionally, the network pharmacology study had been used to analysis the identified ingredients and DKD's clinical diseases. In this work, a total of 121 components and isomers were characterized, including amino acids, phenolic acids, lactones, terpenoids, alkaloids, saponins, flavonoids, and other compounds. Network pharmacology analysis showed that identified compounds, such as ginsenosides and notoginsenosides, crocin I, echinacoside, rutin and verbascoside, could be responsible for the pharmacological activity of DKD by regulating the hormone with related metabolism pathways, estrogen signaling pathways and serotonergic synapse pathways. It could indicate that UHPLC-MS showed obvious superiority used to find the potential bioactive compounds of complicated TCM formula without the process of extraction and isolation.

5.
Protein Expr Purif ; 166: 105503, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31550499

RESUMO

The N-glycosylation process that occurs in the Pichia pastoris protein expression system can have a significant effect on the yield of heterologous glycoproteins secreted from the yeast. The basis of the effect of N-glycosylation on yield, however, has not been elucidated. In order to investigate the effect of N-glycosylation on heterologous protein production, site-directed mutation was performed on five potential N-glycosylation sites of the tetanus toxin fragment C (TetC). Unaltered TetC (wild-TetC) and eight mutants, in which different numbers and locations of N-glycosylation sites were altered, were expressed in P. pastoris GS115. The recombinant target proteins presented different levels of N-glycosylation. The wild Tet-C and 4 mutations sites of putative N-glycosylation (4Gly mutant: N280Q) had the highest level of secreted protein, while 1 mutation of putative N-glycosylation sites (1Gly mutant: N39/64/85/205Q) had the highest level of intracellular, non-secreted heterologous protein. Reducing the number of native N-glycosylation sites decreased the level of glycosylation, as well as the level of secretion. Introduction of a N-glycosylation site at position 320, however, also reduced the level of expression and secretion of recombinant protein. These results indicate that the number and location of N-glycosylation sites jointly have an effect on the expression and secretion of heterologous glycoproteins in P. pastoris.

6.
Zhen Ci Yan Jiu ; 44(9): 649-52, 2019.
Artigo em Chinês | MEDLINE | ID: mdl-31532133

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Baihui" (GV20) and "Zusanli" (ST36) on the expression of stromal cell derived factor-1α (SDF-1α) and CD34 in ischemic cortex tissue of cerebral ische-mia /reperfusion injury (CI/RI) rats, so as to study its mechanisms underlying improving CI/RI. METHODS: Thirty male SD rats were equally and randomly divided into sham operation, model and EA groups (n=10 rats in each group). The CI/RI model was established by occlusion of the middle cerebral artery for 120 min, followed by reperfusion. EA (40 Hz, 1-2 mA) was applied to GV20 and left ST36 for 20 min, once daily for successive 14 days. The neurological deficit severity was assessed by using Longa's and colleagues' methods. The histopathological changes of the ischemic tissues were observed after H.E. staining and the expression of SDF-1α and CD34 in the ischemic cortex tissues was detected by immunohistochemistry. RESULTS: After modeling, the neurological deficit score, and the numbers of SDF-1α and CD34-positive cells in the ischemic cerebral cortex tissue were significantly increased in the model group (P<0.05). Following EA intervention, the increased neurological deficit score was reversed at the 3rd, 7th and 14th day, and the increased SDF-1α and CD34-positive cells were significantly further up-regulated in the EA group (P<0.05). H.E. staining showed tissue edema, widening of the intercellular space, cavitation-like changes, neuronal shrinkage, nuclear pyknosis with hyperchroma or even disappearance, and aggregation of inflammatory and neurogliocytes in the model group. These situations were relatively milder in the EA group. CONCLUSION: EA of GV20 and ST36 can improve neurological function of CI/RI rats, which may be associated with its effect in up-regulating the expression of SDF-1α and CD34 proteins in the ischemic cerebral cortex tissues.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Traumatismo por Reperfusão , Animais , Quimiocina CXCL12 , Masculino , Ratos , Ratos Sprague-Dawley , Células Estromais
7.
J Immunol ; 203(7): 1701-1714, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484729

RESUMO

Intrathecal morphine infusion is often applied to treat chronic pain related to cancer and other conditions. However, persistent pain can be caused by nerve compression because of granuloma formation. In this study, a mouse model of morphine-induced granuloma formation by intrathecal catheterization morphine infusion into the atlanto-occipital membrane of the foramen magnum was established in wild-type mice, MrgprB2 mutant (MrgprB2-/-) mice, and in mast cell-deficient W-sash c-kit mutant (KitW-sh/W-sh) mice. Heat-related pain after surgery was performed to investigate the antipain effect of morphine. H&E staining and immunofluorescence staining of the spinal cord were applied to analyze the mechanism of granuloma formation. Morphine-induced mast cell degranulation was assessed by measuring the Ca2+ influx and mediator release. Anaphylactoid reactions were measured after s.c. morphine infusion to the paws. Chemokine release by mast cells was determined by Human XL Cytokine Array. Experiments with wild-type, MrgprB2 mutant, and mast cell-deficient W-sash c-kit mutant mice demonstrated that morphine activated mast cells and inflammatory cell aggregation through MrgprB2 in intrathecal infusion sites. The chemokine production of human mast cells demonstrated that granuloma formation is correlated with chemokines release. In addition, morphine activated mouse primary mast cells and de novo chemokine synthesis via the MRGPRX2 in human LAD2 cells. We concluded that granuloma formation during intrathecal morphine infusion was associated with MrgprB2/X2. Reducing MRGPRX2 potentially blocks morphine-induced side effects, including granuloma formation.

8.
BMJ Open ; 9(9): e031513, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31542763

RESUMO

OBJECTIVES: To determine the prevalence of physical violence and threats against health workers and the aftermath in tertiary, secondary and primary care facilities in China. DESIGN: A cross-sectional questionnaire study. SETTING: 5 tertiary hospitals, 8 secondary hospitals and 32 primary care facilities located in both urban and rural areas of Zhejiang Province, China, were chosen as the study sites. PARTICIPANTS: A total of 4862 health workers who have contact with patients completed a survey from July 2016 to July 2017. OUTCOME MEASURES: The prevalence of physical violence, threats and Yi Nao, specific forms of physical violence and their aftermath were measured by a self-designed and verified questionnaire. Multivariable logistic regression models were used to examine the association between perceived organisational encouragement of reporting workplace violence (WPV) and physical violence, threats and Yi Nao after controlling for age, sex, level of facility, professional ranking and type of health worker. RESULTS: Among all respondents, 224 (4.6%) were physically attacked and 848 (17.4%) experienced threats in the past year. Respondents in secondary hospitals were more likely to experience physical violence (AOR=3.29, 95% CI 2.21 to 4.89), threats (AOR=1.61, 95% CI 1.32 to 1.98) and Yi Nao (AOR=2.47, 95% CI 2.10 to 2.91), compared with primary care providers. Lack of organisational policies to report WPV was associated with higher likelihood of physical violence (AOR=3.64, 95% CI 2.57 to 5.18) and threats (AOR=2.21, 95% CI 1.76 to 2.78). Among physical violence cases, only 29.1% reported the attack to police mainly because most felt it useless to do so (58.8%). Only 25.7% were investigated and 72.4% of attackers received no punishment. Of all those attacked or threatened, 59.4% wanted to quit current post and 76.0% were fearful of dealing with urgent or severe cases. CONCLUSIONS: Proper management of the aftermath of violence against health workers is inadequate. Formal guidelines for reporting and managing WPV are urgently needed.

9.
Cytotechnology ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31535308

RESUMO

ßKlotho as the major role is a necessary auxiliary protein when fibroblast growth factor 21 (FGF21) binds FGF21 receptors (FGFR) for activating intracellular signaling pathways that ultimately generate biological effects. To achieve the aim of high throughput screening of FGF21 analogues, we established 3T3-L1-ßKlotho cells that could stably express ßklotho protein. The glucose uptake, expression of GLUT1 mRNA and activation of FGF signaling molecules ERK1/2 phosphorylation were detected by GOD-POD assay, real-time PCR analysis and western blotting assay in 3T3-L1-ßKlotho cells and 3T3-L1 adipocytes, respectively. The results showed that FGF21 increased glucose uptake significantly in a dose-dependent and time-dependent manner in 3T3-L1-ßKlotho cells. 3T3-L1-ßKlotho cells stimulated with FGF21 up-regulated the transcriptional levels of GLUT1 mRNA obviously. FGF21 activated the FGF signaling molecules ERK1/2 in 3T3-L1-ßKlotho cells. In addition, the same results were obtained in 3T3-L1 adipocytes. Furthermore, FGF21-stimulated elevation of glucose uptake, GLUT1 mRNA transcription and the phosphorylation of ERK1/2 were dramatically attenuated by pretreatment of cells with FGFR specific inhibitor SU5402 in 3T3-L1-ßKlotho cells. This study demonstrated that the cell model could be applied to high throughput screen FGF21 analogues.

10.
Int J Cancer ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31525266

RESUMO

Chitinase-like proteins (CLP) are chitin-binding proteins that lack chitin hydrolyzing activity, but possess cytokine-like and growth factor-like properties, and play crucial role in intercellular crosstalk. Both human and mice express two members of CLP family: YKL-40 and stabilin-1 interacting chitinase-like protein (SI-CLP). Despite numerous reports indicating the role of YKL-40 in the support of angiogenesis, tumor cell proliferation, invasion and metastasis, the role of its structurally related protein SI-CLP in cancer was not reported. Using gain-of-function approach, we demonstrate in the current study that the expression of recombinant SI-CLP in mouse TS/A mammary adenocarcinoma cells results in significant and persistent inhibition of in vivo tumor growth. Using quantitative immunohistochemistry, we show that on the cellular level this phenomenon is associated with reduced infiltration of tumor-associated macrophages (TAM), CD4+ and FoxP3+ cells in SI-CLP expressing tumors. Gene expression analysis in TAM isolated from SI-CLP-expressing and control tumors demonstrated that SI-CLP does not affect macrophage phenotype. However, SI-CLP significantly inhibited migration of murine bone-marrow derived macrophages and human primary monocytes towards monocyte-recruiting chemokine CCL2 produced in the tumor microenvironment (TME). Mechanistically, SI-CLP did not affect CCL2/CCR2 interaction, but suppressed cytoskeletal rearrangements in response to CCL2. Altogether, our data indicate that SI-CLP functions as a tumor growth inhibitor in mouse breast cancer by altering cellular composition of TME and blocking cytokine-induced TAM recruitment. Taking into consideration weak to absent expression of SI-CLP in human breast cancer, it can be considered as a therapeutic protein to block TAM-mediated support of breast tumor growth. This article is protected by copyright. All rights reserved.

11.
Phys Rev Lett ; 123(8): 087801, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31491225

RESUMO

We present a controlled cascade of self-assemblings of colloidal droplets at a nematic liquid crystal-air interface into large-scale ordered structures. Changing the tilt of the droplet-induced elastic dipoles via its dependence on the nematic film thickness, we are able to control the dipole-dipole interaction and thus the self-assembling regime. For a progressively large tilt, droplets form anisotropic lattices, which then transform into arrays of repulsive chains, then to bands of half-period-shifted densely bound chains. These structures with chain order at the inner scale aggregate into different large-scale clusters that have a pronounced circular pattern and are stabilized by the many-body elastocapillary attraction.

12.
Surg Radiol Anat ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506842

RESUMO

PURPOSE: The aim of this study was to determine the anatomical variations of the superior transverse scapular ligament (STSL) for better understanding the possible predisposing factors for suprascapular nerve entrapment. METHODS: The study was using fifty 10% formalin solution-fixed human cadaveric shoulders. After dissection of the suprascapular region, the length, medial width, lateral width and middle width of the suprascapular opening were measured for each STSL. RESULTS: The STSL displayed six types as: (1) band-shaped in 11 cases; (2) fan-shaped in 27 cases; (3) triangular-shaped in 5 cases; (4) linear type in 2 cases; (5) bifid in 1 case; (6) absent in 1 case. The ossified type of STSL was found in 3 cases. There were statistically significant differences in the length (P = 0.009), medial width (P = 0.001), lateral width (P = 0.029) of the three types of fan-shaped, band-shaped and triangular-shaped. However, there was no statistical difference in the middle width of the suprascapular opening of the three types (P = 0.340). CONCLUSION: Knowing the morphological features and variations of the STSL is important for better understanding the anatomical conditions, which could be taken into consideration during open suprascapular operations or arthroscopic decompressions.

13.
Opt Express ; 27(15): 21646-21651, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510237

RESUMO

We demonstrate an improved approach to integrate various color filters on a chip-scale by using stepwise metal-insulator-metal FP cavities. The cavity is composed of a thick silver mirror, an SU8 gap layer of controlled thickness, and a thin nickel layer. Reflective colors from red to blue can be generated from these filters through a simple UV lithography process. The filters were also fabricated on a flexible substrate which could be incorporated into wearable devices. This method can realize large-scale filter arrays with simple processing and may facilitate the use of structural color filters in displays and sensing.

14.
J Neurovirol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31512144

RESUMO

Enterovirus A71 (EV-A71) is the major cause of severe hand-foot-and-mouth diseases (HFMD), especially encephalitis and other nervous system diseases. EV-A71 capsid protein VP1 mediates virus attachment and is the important virulence factor in the EV-A71pathogenesis. In this study, we explored the roles of VP1 in the permeability of blood-brain barrier (BBB). Sera albumin, Evans blue, and dextran leaked into brain parenchyma of the 1-week-old C57BL/6J mice intracranially injected with VP1 recombinant protein. VP1 also increased the permeability of the brain endothelial cells monolayer, an in vitro BBB model. Tight junction protein claudin-5 was reduced in the brain tissues or brain endothelial cells treated with VP1. In contrast, VP1 increased the expression of virus receptor vimentin, which could be blocked with VP1 neutralization antibody. Vimentin expression in the VP1-treated brain endothelial cells was regulated by TGF-ß/Smad-3 and NF-κB signal pathways. Moreover, vimentin over-expression was accompanied with compromised BBB. From these studies, we conclude that EV-A71 virus capsid protein VP1 disrupted BBB and increased virus receptor vimentin, which both may contribute to the virus entrance into brain and EV-A71 CNS infection.

15.
Hum Mol Genet ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31518400

RESUMO

Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularization. To further investigate the causes and histopathology of exudative AMD, we conditionally induced hypoxia in a novel preclinical AMD model (Pde6gcreERT2/+;Vhl-/-) by targeting Vhl and used multimodal imaging and immunohistochemistry to track the development of hypoxia-induced neovascularization. In addition to developing a preclinical model that phenocopies exudative AMD, our studies revealed that the photoreceptor hypoxic response initiates and drives Type 3 neovascularization, mainly in the outer retina. Activation of the VHL-HIF1a-VEGF-EPO pathway in the adult retina led to long-term neovascularization, retinal hemorrhages, and compromised retinal layers. Our novel preclinical model would accelerate the testing of therapies that use metabolomic approaches to ameliorate AMD.

16.
PLoS One ; 14(9): e0221827, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532782

RESUMO

Chloroplasts significantly influence species phylogenies because of their maternal inheritance and the moderate evolutionary rate of their genomes. Avocado, which is a member of the family Lauraceae, has received considerable attention from botanists, likely because of its position as a basal angiosperm. However, there is relatively little avocado genomic information currently available. In this study, six complete avocado chloroplast genomes from three ecological races were assembled to examine the sequence diversity among the three avocado ecological races. A comparative genomic analysis revealed that 515 simple sequence repeat loci and 176 repeats belonging to four other types were polymorphic across the six chloroplast genomes. Three highly variable regions (trnC-GCA-petN, petN-psbM, and petA-psbJ) were identified as highly informative markers. A phylogenetic analysis based on 79 common protein-coding genes indicated that the six examined avocado accessions from three ecological races form a monophyletic clade. The other three genera belonging to the Persea group clustered to form a sister clade with a high bootstrap value. These chloroplast genomes provide important genetic information for future attempts at identifying avocado races and for the related biological research.

17.
Surg Radiol Anat ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31563971

RESUMO

PURPOSE: The connective tissue between suboccipital muscles and the cervical spinal dura mater (SDM) is known as the myodural bridge (MDB). However, the adjacent relationship of the different connective tissue fibers that form the MDB remains unclear. This information will be highly useful in exploring the function of the MDB. METHODS: The adjacent relationship of different connective tissue fibers of MDB was demonstrated based upon three-dimensional visualization model, P45 plastinated slices and histological sections of human MDB. RESULTS: We found that the MDB originating from the rectus capitis posterior minor muscle (RCPmi), rectus capitis posterior major muscle (RCPma) and obliquus capitis inferior muscle (OCI) in the suboccipital region coexists. Part of the MDB fibers originate from the ventral aspect of the RCPmi and, together with that from the cranial segment of the RCPma, pass through the posterior atlanto-occipital interspace (PAOiS) and enter into the posterior aspect of the upper cervical SDM. Also, part of the MDB fibers originate from the dorsal aspect of the RCPmi, the ventral aspect of the caudal segment of the RCPma, and the ventral aspect of the medial segment of the OCI, enter the central part of the posterior atlanto-axial interspace (PAAiS) and fuse with the vertebral dura ligament (VDL), which connects with the cervical SDM. CONCLUSIONS: Our findings prove that the MDB exists as a complex structure which we termed the 'myodural bridge complex' (MDBC). In the process of head movement, tensile forces could be transferred possibly and effectively by means of the MDBC. The concept of MDBC will be beneficial in the overall exploration of the function of the MDB.

18.
Mol Genet Genomic Med ; 7(10): e00906, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429517

RESUMO

BACKGROUND: Mutations of human androgen receptor (AR) gene are responsible for androgen insensitivity syndrome (AIS). Variable phenotypes and androgen receptor binding activity have permitted the classification of AIS into complete (CAIS), partial (PAIS), and minimal or mild (MAIS) forms. Somatic mosaicism in AIS is a rare condition which happened when de novo mutations occur after the zygotic stage. METHODS: Clinical evaluation, hormone measurements, and molecular analysis were performed to diagnose the patient in the study. RESULTS: A 46, XY girl who conceived through in vitro fertilization (IVF), presented with partial virilization of external genitalia, was found to have the p.C620R in heterozygosity. The variant p.C620R of AR has been previously reported in a patient with completely feminized external genitalia, which was inherited from the heterozygote carrier mother. Mutation analysis of the mother of our patient revealed that the variant was de novo and presented as a somatic mosaicism which indicated an insufficient amount of wild-type AR in our patient. CONCLUSION: This is the first case that AIS was caused by de novo mutation of AR in a 46, XY Disorder of Sexual Development (DSD) patient by the assisted reproduction technique (ART). The phenotype of partial virilization could be explained by AR mutation in somatic mosaicism.

19.
Int J Mol Med ; 44(4): 1357-1365, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432092

RESUMO

It has been demonstrated that miR­222 is upregulated in human intervertebral disc (IVD) degeneration tissues; however, the underlying mechanisms remain unclear. In this study, we aimed to elucidate the mechanisms of action of miR­222 in IVD tissues. Nucleus pulposus (NP) cells were treated with lipopolysaccharide (LPS) to simulate IVD degeneration. The expression level of miR­222 was detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) in cells and tissues. Cell apoptosis was analyzed by flow cytometry. Additionally, western blot analysis was used to determine the levels of Toll­like receptor 4 (TLR4), Iκß­alpha (IκBα) and p65. Interleukin (IL)­1ß, tumor necrosis factor­α (TNF­α) and IL­6 protein expression levels were determined by enzyme­linked immunosorbent assay (ELISA). The target gene of miR­222 was determined by TargetScan7.2 and dual luciferase reporter gene analysis. Western blot analysis and RT­qPCR were used to determine the mRNA and protein levels of tissue inhibitor of metalloproteinase 3 (TIMP3). The mRNA expression level of miR­222 was found to be increased in IVD tissues and in LPS­stimulated cells, and its expression was positively associated with the clinical MRI grade. In vitro, apoptosis was promoted/inhibited by miR­222 mimics/inhibitors. Transfection with miR­222 mimics/inhibitors significantly increased/decreased the production of TNF­α, IL­1ß and IL­6 and suppressed/enhanced collagen II and aggrecan expression. The protein levels of TLR4, p­IκΒα and p­p65 were upregulated/downregulated by transfection with the mimics/inhibitors. In addition, it was demonstrated that TIMP3 was a direct target gene of miR­222, and was negatively regulated by miR­222 in NP cells. The silencing of TIMP3 reversed the inhibitory effects of miR­222 inhibitor on cell apoptosis, which was induced by LPS. Thus, on the whole, the findings of this study demonstrate that miR­222 functions as a promoter of IVD development, partly via the regulation of TIMP3.

20.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1126-1127: 121737, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377565

RESUMO

Gamboge, a dried resin secreted by Garcinia hanburyi Hook. f. (Guttiferae), possesses remarkable anticancer activity. However, due to toxicity, it must be processed before use in clinics. Xanthones are the main bioactive ingredients in gamboge. In order to elucidate the influence of processing technology on pharmacological properties of gamboge, an efficient, sensitive, and selective ultra-performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-MS/MS) method of five critical xanthones, including ß-morellic acid (ß-MA), isogambogenic acid (IGNA), gambogenic acid (GNA), R-gambogic acid (GA), and S-GA in rat plasma was established for a comparative pharmacokinetics study of these xanthones after oral administration of crude and processed G. hanburyi extracts. The chromatographic separation of these five xanthones along with an internal standard (I.S.) was carried out on a Waters Acquity UPLC BEH C8 column with a gradient elution method using acetonitrile/0.1% formic acid-water as mobile phases. The eluate was detected by multiple-reaction monitoring (MRM) scanning with an electrospray ionization source operating in the positive ionization mode. Sample preparation involved a liquid-liquid extraction of the five analytes with ethyl acetate. Deoxyschizandrin was employed as an internal standard. This assay method was validated for selectivity, linearity, intra-day and inter-day precision, accuracy, recovery, matrix effect, and stability. The results revealed that the calibration curves displayed good linear regression (r > 0.995), and the lower limit of quantification (LLOQ) was <5.52 ng/mL for each analyte. The intra-day and inter-day precision (RSD) of the five xanthones at low, medium, and high levels was <10.58%, and the bias of the accuracy ranged from -8.54 to 10.2%. All other parameters fulfilled the FDA criteria for bioanalytical validation. In addition, the assay was successfully applied to the determination and pharmacokinetic study of these five xanthones after oral administration of crude and processed gamboge. Furthermore, Cmax of GNA and AUC0-t of IGNA were increased significantly (P < 0.05) after processing, while AUC0-t of ß-MA, R-GA, and S-GA decreased remarkably (P < 0.05), which suggested that processing exerted different effects on the absorption of xanthones. The results might be valuable for the clinical reasonable application and understanding the processing mechanism of gamboge.

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