Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 929
Filtrar
1.
J Hum Genet ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427951

RESUMO

Human Y-chromosome haplogroup C2b-F1067 is one of the dominant paternal lineages of populations in Eastern Eurasia. In order to explore the origin, diversification, and expansion of this haplogroup, we generated 206 new Y-chromosome sequences from C2b-F1067 males and coanalyzed 220 Y-chromosome sequences of this haplogroup. BEAST software was used to reconstruct a revised phylogenetic tree of haplogroup C2b-F1067 with age estimates. The revised phylogeny of C2b-F1067 included 155 sublineages, 1986 non-private variants, and >6000 private variants. The age estimation suggested that the initial splitting of C2b-F1067 happened at about 32.8 thousand years ago (kya) and the major sublineages of this haplgroup experienced continuous expansion in the most recent 10,000 years. We identified numerous sublineages that were nearly specific for Korean, Mongolian, Chinese, and other ethnic minorities in China. In particular, we evaluated the candidate-specific lineage for the Dayan Khan family and the Confucius family, the descendants of the ruling family of the Chinese Shang dynasty. These findings suggest that ancient populations with varied C2b-F1067 sublineages played an important role during the formation of most modern populations in Eastern Eurasia, and thus eventually became the founding paternal lineages of these populations.

2.
Toxicon ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32428516

RESUMO

This study evaluated the performance of an easy-cultivation device for the mass culture of Alexandrium minutum (A. minutum), a dinoflagellate that produces paralytic shellfish toxins (PSTs). Five culture conditions including three different sizes of containers (250 mL conical flask, 500 mL beaker, and 20 L jar) in two different environments (out-incubator and incubator) were compared in terms of growth and PSTs production. Compared with the incubator environment, the out-incubator environment had more fluctuations in temperature and light intensity. Results showed that the cell densities of A. minutum increased in all groups, especially in the conical flask (I, out-incubator, 6.29×106 cells/mL) and the beaker (IV, incubator, 7.28×106 cells/mL). When cultured in the 20 L jar under out-incubator condition, the algae had the lowest cell density (2.82×106 cells/mL) but the highest toxicity (93.42 ±â€¯2.55×10-6 MU/cell). The negative correlation between average growth rate and single-cell toxicity could be explained by biocompatibility, thereby indicating that the low growth rate led to high toxicity. HPLC-FLD showed that the cellular toxicity increased due to the quantitative increase in GTX1/4, which are the more toxic derivatives. The PSTs types consistently contained GTX1/4 and GTX2/3. The differences in algae growth and toxin-production could be due to changes in bacteria (out-incubator) and CO2 (incubator) with vessel size. The effects of environmental factors on algae are strain specific. The out-incubator device can be applied for large-scale cultivation of A. minutum considering the algae density and toxin-producing ability.

3.
Oncogene ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439864

RESUMO

Long noncoding RNAs (lncRNAs) were demonstrated to play important roles in gene regulation and cancer progression. However, the functional roles of lncRNAs and the detailed mechanisms underlying gastric cancer (GC) progression remain largely unclear. Here, we identified a novel cancer-related lncRNA, termed lncRNA GCMA (Gastric Cancer metastasis-associated lncRNA), which was upregulated in GC tissues with lymph node metastasis (LNM) compared with tissues without LNM. High expression of GCMA was significantly associated with poor prognosis of patients with GC. Luciferase assays, bioinformatics analyses and chromatin immunoprecipitation (ChIP) assays indicated that SP1 transcription factor directly bound to the GCMA promoter region and activated its transcription. Functionally, upregulation of GCMA dramatically promoted GC cells proliferation, migration and invasion in vitro, whereas knockdown of GCMA elicited the opposite function. Consistently, stable knockdown of GCMA inhibited tumor proliferation, invasion and metastasis in vivo. Mechanistically, by using bioinformatics analyses, RNA binding protein immunoprecipitation (RIP) assays, luciferase assays and western-blot assays, GCMA was demonstrated to function as a competing endogenous RNA (ceRNA) via competitively absorbing miR-124 and miR-34a to upregulate slug and snail, thereby induced epithelial-mesenchymal transition (EMT) and GC cell metastasis in vitro and in vivo. Collectively, these results demonstrate that GCMA functions as an oncogenic lncRNA that may serve as a potential prognostic biomarker for GC and shed new lights on targeted therapy of GC in the future.

4.
Cell ; 181(4): 936-953.e20, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32386544

RESUMO

Recent large-scale collaborations are generating major surveys of cell types and connections in the mouse brain, collecting large amounts of data across modalities, spatial scales, and brain areas. Successful integration of these data requires a standard 3D reference atlas. Here, we present the Allen Mouse Brain Common Coordinate Framework (CCFv3) as such a resource. We constructed an average template brain at 10 µm voxel resolution by interpolating high resolution in-plane serial two-photon tomography images with 100 µm z-sampling from 1,675 young adult C57BL/6J mice. Then, using multimodal reference data, we parcellated the entire brain directly in 3D, labeling every voxel with a brain structure spanning 43 isocortical areas and their layers, 329 subcortical gray matter structures, 81 fiber tracts, and 8 ventricular structures. CCFv3 can be used to analyze, visualize, and integrate multimodal and multiscale datasets in 3D and is openly accessible (https://atlas.brain-map.org/).

5.
Biol Trace Elem Res ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32418160

RESUMO

Women with gestational diabetes mellitus (GDM) may have lower serum selenium levels than healthy controls, which may be associated with preterm birth. We explored the association of serum selenium levels in early pregnancy with the risk of GDM and preterm birth among Chinese women. We included 398 women with a singleton pregnancy, who were followed up prospectively from the first prenatal visit until delivery. Serum selenium levels were measured in the first trimester. After delivery, data concerning mothers and their children were sourced from medical records by researchers who were blind to the participants' selenium status. Of the 398 women, 71 (17.8%) had GDM, 21(5.3%) had preterm birth, and 266 (66.8%) had selenium deficiency (serum selenium < 70 µg/L). Women in the upper three quartiles of serum selenium level did not have a significantly lower risk of GDM or preterm birth than those in the lowest quartile after adjustment for covariates (all p > 0.05). When serum selenium levels were classified as normal or deficient, the risk of GDM or preterm birth among women with normal serum selenium levels was still not lower than that of women with deficient serum selenium levels after adjustment for covariates (all p > 0.05). Although selenium deficiency was common in the Chinese women in our cohort, our results indicate that low serum selenium level during early pregnancy may not be a strong predictor of the risk of GDM and preterm birth. However, our sample size was small, and future studies with larger populations are warranted.

6.
Behav Brain Res ; 390: 112660, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32387350

RESUMO

Exposure to maternal high-fat (HF) diet during gestation and lactation alters adult offspring's feeding behavior and diet preference. However, the impact of maternal exercise on offspring's diet preference and reward system development is less studied. In this study, we investigate the effect of perinatal maternal exercise on the development of diet preference, dopamine- and opioid-related gene expression in the central reward system in female offspring from HF-fed Sprague-Dawley rat dams. We found maternal HF diet did not alter adult offspring HF preference, but influenced offspring's dopamine and opioid system both at weaning and in adulthood, and these offspring retained higher body weight in adulthood. However, offspring from dams exposed to both HF diet and exercise during gestation and lactation had normalized body weight, decreased fat mass and lower HF-diet preference but increased energy intake in adulthood. The dopamine- and opioid-related gene expression in central reward system and POMC expression in hypothalamus was elevated in these adult offspring. We conclude that maternal exercise during gestation and lactation can potentially overcome the negative effects of perinatal exposure to HF diet in female offspring by altering their diet preference, central reward system signaling and hypothalamus neuropeptide expression.

7.
Cell Rep ; 31(7): 107648, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32433957

RESUMO

Subicular regions play important roles in spatial processing and many cognitive functions, and these are mainly attributed to the subiculum (Sub) rather than the prosubiculum (PS). Using single-cell RNA sequencing, we identify 27 transcriptomic cell types residing in sub-domains of the Sub and PS. Based on in situ expression of reliable transcriptomic markers, the precise boundaries of the Sub and PS are consistently defined along the dorsoventral axis. Using these borders to evaluate Cre-line specificity and tracer injections, we find bona fide Sub projections topographically to structures important for spatial processing and navigation. In contrast, the PS sends its outputs to widespread brain regions crucial for motivation, emotion, reward, stress, anxiety, and fear. The Sub and PS, respectively, dominate dorsal and ventral subicular regions and receive different afferents. These results reveal two molecularly and anatomically distinct circuits centered in the Sub and PS, respectively, providing a consistent explanation for historical data and a clearer foundation for future studies.

8.
Cochrane Database Syst Rev ; 4: CD012253, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32309880

RESUMO

BACKGROUND: This is an updated version of the original Cochrane Review published in 2018, Issue 5. Epilepsy affects over 70 million people worldwide, and nearly a quarter of patients with seizures have drug-resistant epilepsy. People with drug-resistant epilepsy have increased risks of premature death, injuries, psychosocial dysfunction, and a reduced quality of life. OBJECTIVES: To assess the efficacy and tolerability of clonazepam when used as an add-on therapy for adults and children with drug-resistant focal onset or generalised onset epileptic seizures, when compared with placebo or another antiepileptic agent. SEARCH METHODS: For the latest update we searched the following databases on 4 June 2019: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid) 1946 to 3 June, 2019. The Cochrane Register of Studies (CRS Web) includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised or quasi-randomised, controlled trials from Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Double-blind randomised controlled studies of add-on clonazepam in people with resistant focal or generalised onset seizures, with a minimum treatment period of eight weeks. The studies could be of parallel or cross-over design. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted relevant data, and assessed trial quality. We contacted study authors for additional information. MAIN RESULTS: We found no double-blind randomised controlled trials which met the inclusion criteria. AUTHORS' CONCLUSIONS: There is no evidence from double-blind randomised controlled trials for or against the use of clonazepam as an add-on therapy for adults and children with drug-resistant focal or generalised onset epileptic seizures. Since the last version of this review no new studies have been found.

9.
Bioorg Med Chem ; 28(11): 115498, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32291146

RESUMO

δ-tocotrienol (DT3), a member of vitamin E family, has been shown to have a potent radio-protective effect. However, its application as a radioprotectant is limited, at least in part, by its short plasma elimination half-life and low bioavailability. In an effort to increase the metabolic stability of DT3, a deuterium substituted DT3 derivative, d6-DT3, was designed and synthesized. d6-DT3 showed improved in vitro and in vivo metabolic stability compared to DT3. The unexpected lower potency of d6-DT3 in inducing granulocyte-colony stimulating factor (G-CSF) production in mouse revealed that the metabolite(s) of DT3 might play a major role in inducing G-CSF induction.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32346936

RESUMO

Hierarchical FeCoS2 -CoS2 double-shelled nanotubes have been rationally designed and constructed for efficient photocatalytic CO2 reduction under visible light. The synthetic strategy, engaging the two-step cation-exchange reactions, precisely integrates two metal sulfides into a double-shelled tubular heterostructure with both of the shells assembled from ultrathin two-dimensional (2D) nanosheets. Benefiting from the distinctive structure and composition, the FeCoS2 -CoS2 hybrid can reduce bulk-to-surface diffusion length of photoexcited charge carriers to facilitate their separation. Furthermore, this hybrid structure can expose abundant active sites for enhancing CO2 adsorption and surface-dependent redox reactions, and harvest incident solar irradiation more efficiently by light scattering in the complex interior. As a result, these hierarchical FeCoS2 -CoS2 double-shelled nanotubes exhibit superior activity and high stability for photosensitized deoxygenative CO2 reduction, affording a high CO-generating rate of 28.1 µmol h-1 (per 0.5 mg of catalyst).

11.
J Nutr Biochem ; 80: 108377, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32278117

RESUMO

Deteriorated nicotinamide adenine dinucleotide (NAD+)/sirtuins (SIRTs) metabolism in adipose tissue is implicated in diet-induced obesity, while calorie restriction (CR)-induced beneficial effects require sufficient NAD+ biosynthesis. Mechanistic links have not been defined. This study aims to identify changes of specific components of NAD+/SIRTs system in white adipose tissue (WAT) and brown adipose tissue (BAT) of mice upon energy imbalance, focusing on key enzymes in NAD+ salvage (Nampt, Nmnat1, Nrk1), clearance (Nnmt, Aox1, Cyp2e1) and consumption pathways (Sirt1, Sirt2, Sirt3, Sirt6, Parp1). Male C57BL/6J mice were fed ad libitum with the standard laboratory chow diet, high-fat diet (HFD) or 40% CR diet, respectively. The epididymal and inguinal WAT (eWAT and iWAT) and interscapular BAT (iBAT) were harvested for histological, NAD+ assay, gene and protein expression analysis after 16 weeks of dietary regimen. HFD decreased, while CR increased, the NAD+ and NADH levels in eWAT, iWAT and iBAT. NAD+ content negatively correlated with plasma cholesterol, TNF-α levels and calorie intake, while it positively correlated with plasma adiponectin level. The change trend of SIRT1 is quite the same as that of NAD+/NADH ratio. Nmnat1 gene is sensitive to energy imbalance in WAT but not in BAT. Nrk1 gene expression was decreased in eWAT and iWAT but increased in iBAT of HFD mice. Nnmt mRNA and protein abundance was increased in iWAT of HFD mice. Nampt, Cyp2e1 and Sirt3 were the most robust genes responding to energy imbalance. In summary, adipose tissue responds to long-term energy excess or shortage with depot-specific transcriptional activation or repression of NAD+/SIRTs metabolic components.

12.
Acta Biomater ; 108: 313-325, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32268236

RESUMO

Tumor hypoxia is believed to be a factor limiting successful outcomes of oxygen-consuming cancer therapy, thereby reducing patient survival. A key strategy to overcome tumor hypoxia is to increase the prevalence of oxygen at the tumor site. Oxygen-containing microbubbles/nanobubbles have been developed to supply oxygen and enhance the effects of therapies such as radiotherapy and photodynamic therapy. However, the application of these bubbles is constrained by their poor stability, requiring major workarounds to increase their half-lives. In this study, we explore the potential of biogenic gas vesicles (GVs) as a new kind of oxygen carrier to alleviate tumor hypoxia. GVs, which are naturally formed, gas-filled, protein-shelled compartments, were modified on the surface of their protein shells by a layer of liposome. A substantial improvement of oxygen concentration was observed in hypoxic solution, in hypoxic cells, as well as in subcutaneous tumors when lipid-GVs(O2) were added/tail-injected. Significant enhancement of tumor cell apoptosis and necrosis was also observed during photodynamic therapy (PDT) in the presence of lipid-GVs(O2) both in vitro and in vivo. Lipid-GVs(O2) alone induced no obvious change in cell viability in vitro or any apparent pathological abnormalities after mice were tail-injected with them. In all, lipid-GVs exhibited promising performance for intravenous gas delivery, enhanced PDT efficacy and low toxicity, a quality that may be applied to alleviate hypoxia in cancers, as well as hypoxia-related clinical treatments. STATEMENT OF SIGNIFICANCE: The development of stable oxygen-filled micro/nanobubbles capable of delivering oxygen to tumor sites is a major hurdle to enhancing the efficacy of cancer therapy. Currently, micro/nanobubbles are limited by their instability when oxygen is encapsulated, creating a large pressure gradient and surface tension. To improve stability, we modified the surfaces of GVs, a biogenic stable nanoscale hollow structure, as a new class of oxygen carriers. Lipid-coated GVs were found to be stable in solution and effective O2 carriers. This will overcome the limitations of coalescence, short circulation time of synthetic bubbles during application. Our surface-modified GVs demonstrated low toxicity in vitro cell in vivo, while also being able to overcome hypoxia-associated therapy resistance when combined with photodynamic therapy.

13.
Nat Commun ; 11(1): 1996, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332723

RESUMO

Small molecules that selectively kill senescent cells (SCs), termed senolytics, have the potential to prevent and treat various age-related diseases and extend healthspan. The use of Bcl-xl inhibitors as senolytics is largely limited by their on-target and dose-limiting platelet toxicity. Here, we report the use of proteolysis-targeting chimera (PROTAC) technology to reduce the platelet toxicity of navitoclax (also known as ABT263), a Bcl-2 and Bcl-xl dual inhibitor, by converting it into PZ15227 (PZ), a Bcl-xl PROTAC, which targets Bcl-xl to the cereblon (CRBN) E3 ligase for degradation. Compared to ABT263, PZ is less toxic to platelets, but equally or slightly more potent against SCs because CRBN is poorly expressed in platelets. PZ effectively clears SCs and rejuvenates tissue stem and progenitor cells in naturally aged mice without causing severe thrombocytopenia. With further improvement, Bcl-xl PROTACs have the potential to become safer and more potent senolytic agents than Bcl-xl inhibitors.

14.
J Ethnopharmacol ; 256: 112799, 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32243989

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sulfur-fumigation has been developed to prevent insects and molds during post-harvest handling of Panax ginseng C.A. Mey (ginseng) in the near decades. Our previous study indicated sulfur-fumigation could transform ginsenosides, the active components of ginseng, into sulfur-containing derivatives (SFCDs), the artifacts with unknown toxicity. However, whether the biotransformation could be occurred and absorption characteristics between ginsenosides and SFCDs are still needed to further investigate. AIM OF THE STUDY: To evaluate the effect of sulfur-fumigation process on ginseng through comparing the metabolic profile and absorption characteristics between ginsenoside Rg1, Re and their SFCDs. MATERIALS AND METHODS: Intestinal microflora and liver S9 fraction were utilized to compare the metabolic profile, and single-pass intestinal perfusion and Caco-2 cell models were applied to compare the absorption characteristics, between Rg1, Re and their SFCDs. RESULTS: Rg1 and Re were metabolized to 7 none sulfur-containing metabolites, while their SFCDs were metabolized to 18 sulfur-containing metabolites. The intestinal absorption and transport of Rg1 and Re were much greater than their SFCDs. Besides, the uptakes of Rg1 and Re were transport-dependent, but their SFCDs were non-transport-dependent. CONCLUSION: Ginsenosides and their SFCDs could not be bio-transformed with each other and their absorption characteristics were quite different, which suggested that sulfur-fumigation is not a feasible post-harvest process of ginseng.

15.
Exp Anim ; 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32336744

RESUMO

Schisandrin, an active component extracted from Schisandra chinensis (Turcz.) Baill has been reported to alleviate the cognitive impairment in neurodegenerative disorder like Alzheimer's disease (AD). However, the mechanism by which schisandrin regulates the cognitive decline is still unclear. In our study, intracerebroventricular injection of streptozotocin (STZ) was employed to establish AD model in male Wistar rats, and indicated dose of schisandrin was further administered. The Morris water maze test was performed to evaluate the ability of learning and memory in rats with schisandrin treatment. The results indicated that schisandrin improved the capacity of cognition in STZ-induced rats. The contents of pro-inflammatory cytokines in brain tissue were determined by ELISA, and the expressions of these cytokines were assessed by western-blot and immunohistochemistry. The results showed that treatment of schisandrin significantly reduced the production of inflammation mediators including tumor necrosis factor-α, interleukin-1ß and interleukin-6. Further study suggested a remarkable decrease in the expressions of ER stress maker proteins like C/EBP-homologous protein, glucose-regulated protein 78 and cleaved caspase-12 in the presence of schisandrin, meanwhile the up-regulation of sirtuin 1 (SIRT1) was also observed in the same group. Additionally, the results of western-blot and EMSA demonstrated that schisandrin inhibited NF-κB signaling in the brain of STZ-induced rats. In conclusion, schisandrin ameliorated STZ-induced cognitive dysfunction, ER stress and neuroinflammation which may be associated with up-regulation of SIRT1. Our study provides novel mechanisms for the neuroprotective effect of schisandrin in AD treatment.

16.
JMIR Form Res ; 4(4): e12098, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32314975

RESUMO

BACKGROUND: Smartphone-based dating apps are rapidly transforming how people seek potential sexual and romantic partners. However, they can also increase the risk of unsafe sexual behaviors, harassment, and infringement of personal privacy. Current research on interventions for safer dating app use remains insufficient. OBJECTIVE: The goal of this study was to describe the development of an intervention for safer dating app usage using crowdsourcing and peer-led approaches. METHODS: This paper describes the development of an intervention program designed to promote safer dating app use among college students. Crowdsourcing and peer-led approaches were adopted during key stages of the development process. Focus group discussions were held to assess the experience and needs of dating app users. A crowdsourcing contest then solicited ideas for performance objectives for the intervention. These objectives were grouped to further identify practical strategies. A one-day intensive workshop was subsequently held with peer mentors to brainstorm ideas for the production of creative interventional materials. The intervention programs were produced and tested in a pilot study. The app's effectiveness will be evaluated in a cluster randomized controlled trial. RESULTS: The intervention program consists of a risk assessment tool, a first-person scenario game, and four short videos. The risk assessment tool, comprised of 14 questions, will give the participant a score to determine their level of risk of adverse events when using dating apps. The scenario game is a first-person simulation game where the players are presented with choices when faced with different scenarios. The short videos each last 2-4 minutes, with points of discussion aimed at addressing the risks of using dating apps. The programs were piloted and were found to be relatable and helpful when further modifications were made. CONCLUSIONS: Potential challenges identified during the development process included data management and analysis, sustaining peer mentors' interests and participation, and balancing between providing more information and perpetuating social stigma around dating app use. By integrating new approaches, such as crowdsourcing and the peer-led approach, in developing an intervention for safer dating app use, our development process provides a viable model for developing future interventions to address the risks associated with dating app use.

18.
Radiat Res ; 193(4): 394-405, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32126187

RESUMO

The current treatment for liver failure is restricted to surgical liver transplantation, which is technically complicated, limited by the shortage of available organs and presents major risks to the patient. Bone marrow mesenchymal stem cells (BMSCs) represent promising sources of hepatocyte-like cells for cell transplantation treatment. However, a safe and efficient induction method for their differentiation remains to be defined. Here we further optimized an effective technique by combining high-dose treatment with hepatocyte growth factor (HGF) and ultrasound stimulation. The optimized ultrasound parameter (1.0 W/cm2 intensity, 1 MHz frequency, 20% duty cycle, 100 Hz pulse repetition frequency, 60-s irradiation duration, triple times in three days) combined with different HGF doses (10, 20 and 50 ng/ml) was used to treat BMSCs. The results showed that the specific hepatic markers, including α-fetoprotein (αFP/AFP), cytokeratin 18 (CK18), albumin (ALB) and glycogen, were increased in a dose-dependent manner. Their concentration was then further increased when ultrasound irradiation was administered (P < 0.05), as indicated by PCR, Western blot and immunofluorescence staining as well as a glycogen synthesis test. Furthermore, analysis of the hepatocyte-derived chemokines showed elevated stromal cell-derived factor 1alpha (SDF-1α) and C-X-C chemokine receptor type 4 (CXCR4) after HGF treatment. Again, concentrations of those chemokines were further increased by ultrasound radiation (P < 0.05). The observed increased effect was sustained for 21 days. To summarize, we further defined the optimal combination of HGF and ultrasound treatment to increase the differentiation and chemotaxis of BMSCs in a safe, sustained and efficient manner. These findings provide a new perspective for stem cell orientation in the field of tissue engineering.

19.
Fish Shellfish Immunol ; 100: 358-367, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32169665

RESUMO

Class B scavenger receptor type 1 (SRB1) serves as a high-density lipoprotein (HDL) receptor essential for HDL metabolism, and plays vital roles in innate immunity. In this study, the turbot (Scophthalmus maximus) SRB1 was cloned and characterized. The gene structure consists of a coding region of 1,527 bp nucleotides dividing into 13 exons and 12 introns. Such genome structure is highly conserved among teleost fishes. The deduced SRB1 encodes 508 amino acids that mainly has a CD36 transmembrane domain. Tissue distribution of SRB1 showed the lowest expression in liver, while the highest expression was found in intestine. Significantly down-regulation pattern of SmSRB1 expression in intestine was shared after infection with Vibrio anguillarum and Streptococcus iniae. Brach and site models in CODEML program showed that SmSRB1 underwent a conservative evolutionary and three potential positive selected sites 470K, 496E, and 501Y were detected, which requires further investigation and confirmation using base-editing technologies. Subcellular localization demonstrated that turbot SRB1 was distributed in the membrane and cytoplasm. rSmSRB1 showed binding ability in vitro to bacteria, LPS, PGN, LTA and virus. Protein-protein interaction network agrees the function of SRB1 as lipoprotein receptor. Our results indicated SmSRB1 might act as co-receptors to TLRs and NLRs to modulate the immune response to pathogens. Further studies should pay attention to evaluate the specific co-receptor for SRB1 in recognition of different pathogens and selective mechanisms involved.

20.
Nat Commun ; 11(1): 1172, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127543

RESUMO

von Economo neurons (VENs) are bipolar, spindle-shaped neurons restricted to layer 5 of human frontoinsula and anterior cingulate cortex that appear to be selectively vulnerable to neuropsychiatric and neurodegenerative diseases, although little is known about other VEN cellular phenotypes. Single nucleus RNA-sequencing of frontoinsula layer 5 identifies a transcriptomically-defined cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons. Cross-species alignment of this cell cluster with a well-annotated mouse classification shows strong homology to extratelencephalic (ET) excitatory neurons that project to subcerebral targets. This cluster also shows strong homology to a putative ET cluster in human temporal cortex, but with a strikingly specific regional signature. Together these results suggest that VENs are a regionally distinctive type of ET neuron. Additionally, we describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons.


Assuntos
Neurônios/fisiologia , Lobo Temporal/citologia , Transcriptoma , Animais , Encéfalo/citologia , Encéfalo/fisiologia , Eletrofisiologia/métodos , Perfilação da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Camundongos , Neurônios/citologia , Células Piramidais/fisiologia , Telencéfalo/citologia , Lobo Temporal/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA