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1.
J Cell Physiol ; 235(1): 221-231, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31187497

RESUMO

The motility of mesenchymal stem cells (MSCs) is highly related to their homing in vivo, a critical issue in regenerative medicine. Our previous study indicated copper (Cu) might promote the recruitment of endogenous MSCs in canine esophagus defect model. In this study, we investigated the effect of Cu on the motility of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanism in vitro. Cu supplementation could enhance the motility of BMSCs, and upregulate the expression of hypoxia-inducible factor 1α (Hif1α) at the protein level, and upregulate the expression of rho family GTPase 3 (Rnd3) at messenger RNA and protein level. When Hif1α was silenced by small interfering RNA (siRNA), Cu-induced Rnd3 upregulation was blocked. When Rnd3 was silenced by siRNA, the motility of BMSCs was decreased with or without Cu supplementation, and Cu-induced cytoskeleton remodeling was neutralized. Furthermore, overexpression of Rnd3 also increased the motility of BMSCs and induced cytoskeleton remodeling. Overall, our results demonstrated that Cu enhanced BMSCs migration through, at least in part, cytoskeleton remodeling via Hif1α-dependent upregulation of Rnd3. This study provided an insight into the mechanism of the effect of Cu on the motility of BMSCs, and a theoretical foundation of applying Cu to improve the recruitment of BMSCs in tissue engineering and cytotherapy.

2.
Opt Lett ; 44(19): 4698-4701, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31568420

RESUMO

We report fabrication of a multifunctional photonic integrated chip on lithium niobate on insulator, which is achieved by femtosecond laser-assisted chemomechanical polish. We demonstrate a high-extinction-ratio beam splitter, a 1×6 optical switch, and a balanced 3×3 interferometer on the fabricated chip by reconfiguring the microelectrode array integrated with the multifunctional photonic circuit.

3.
Front Med ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31571161

RESUMO

In order to unveil ubiquitin pathway genes (UPGs) that are essential for non-small cell lung cancer (NSCLC) cell proliferation, we recently conducted a siRNA screening experiment to knockdown the expression of 696 UPGs found in the human genome in A549 and H1975 NSCLC cells. We found that silencing of one of the candidates, RFWD3 that encodes an E3 ubiquitin ligase essential for the repair of DNA interstrand cross-links in response to DNA damage, led to dramatic inhibition of NSCLC cell proliferation with significant Z-scores. Knockdown of RFWD3 suppressed colony forming activity of NSCLC cells.We further evaluated the significance of RFWD3 in NSCLCs and found that this gene was more elevated in tumor samples than in paired normal lung tissues and was inversely associated with the clinical outcome of patients with NSCLC. Moreover, RFWD3 expression was significantly higher in smokers than in non-smokers. These results show for the first time that RFWD3 is required for NSCLC cell proliferation and may have an important role in lung carcinogenesis.

4.
Appl Radiat Isot ; 155: 108915, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590101

RESUMO

To develop PET radiotracers for imaging of Alzheimer's disease, a new carbon-11 labeled potent and selective γ-secretase modulator (GSM) has been synthesized. The reference standard tetrahydrobenzisoxazole derivative 8 and its desmethylated precursor 9 were synthesized from cyclohex-2-en-1-one and 3-hydroxy-4-nitrobenzaldehyde in eight and nine steps with 11% and 5% overall chemical yield, respectively. The radiotracer [11C]8 was prepared from its corresponding precursor 9 with [11C]CH3OTf through O-11C-methylation and isolated by RP-HPLC combined with SPE in 45-50% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was 555-740 GBq/µmol.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31600907

RESUMO

Facebook Groups facilitate information exchange and engagement for patients with chronic conditions, including those living with Chronic Obstructive Pulmonary Disease (COPD); however, little is known about how knowledge is diffused throughout these communities. This study aimed to evaluate the content that is available on COPD-related Facebook Groups, as well as the communication (self-disclosures, social support) and engagement (agreement, emotional reaction) strategies used by members to facilitate these resources. Two researchers independently searched the "Groups" category using the terms "COPD", "emphysema", and "chronic bronchitis". Twenty-six closed (n = 23) and public (n = 3) COPD Facebook Groups were identified with 87,082 total members. The vast majority of Group members belonged to closed (n = 84,684; 97.25%) as compared to open (n = 2398; 2.75%) groups. Medications were the most commonly addressed self-management topic (n = 48; 26.7%). While overall engagement with wall posts was low, the number of "likes" (an indicator of agreement) was significantly greater for wall posts that demonstrated social support as compared to posts that did not (p < 0.001). Findings from this study showed that COPD Facebook group members share specific disease-related experiences and request information about select self-management topics. This information can be used to improve the quality of self-management support provided to members of popular COPD Facebook groups.

6.
Molecules ; 24(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600996

RESUMO

Acetaminophen (APAP) overdose is very common worldwide and has been widely recognized as the leading cause of drug-induced liver injury in the Western world. In our previous investigation, auriculatone, a natural product firstly obtained from Aster auriculatus, has demonstrated a potent protective effect against APAP-induced hepatotoxicity in HL-7702 cells. However, the poor water solubility and low bioavailability restrict its application. Auriculatone sulfate (AS) is a sulfated derivative of auriculatone with highly improved water-solubility. Hepatoprotective effects against APAP-induced liver injury (AILI) showed that intragastric pretreatment with AS at 50 mg/kg almost completely prevented mice against APAP-induced increases of serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and ATPase. Histological results showed that AS could protect the liver tissue damage. In addition, AS pretreatment not only significantly retained hepatic malondialdehyde and the activities of glutathione, superoxide dismutase, and glutathione peroxidase at normal levels, but also markedly suppressed the increase of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 levels in mouse liver caused by overdose APAP. Immunohistochemical analysis showed that AS obviously attenuated the expression of CD45 and HNE in liver tissue. Further mechanisms of action investigation showed that inhibition of cytochrome P450 3A11 (CYP 3A11) and CYP2E1 enzymatic activities (but not that of CYP1A2) was responsible for APAP bioactivation. In conclusion, AS showed a hepatoprotective effect against AILI through alleviating oxidative stress and inflammation and inhibiting CYP-mediated APAP bioactivation. It may be an effective hepatoprotective agent for AILI and other forms of human liver disease.

7.
Rev Cardiovasc Med ; 20(3): 179-186, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601092

RESUMO

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathyis a rare form of inherited cerebral small vessel disease associated with mutations in the high-temperature requirement serine peptidase A1 gene. As of now, only about 50 cases have been reported. In 2012, our group reported a family with a novel mutant of the high-temperature requirement serine peptidase A1 gene in China for the first time. To further explore the molecular pathogenesis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, a recombination mouse model expressed human high-temperature requirement serine peptidase A1 gene mutant identified by our group was generated using the Donor & Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 system and termed the Mut-high-temperature requirement serine peptidase A1 geneL364P mouse model. Results show that Mut-high-temperature requirement serine peptidase A1 geneL364P mice present similar pathological characteristics to patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, suggesting that the Mut-high-temperature requirement serine peptidase A1 geneL364P mouse model was generated successfully. Moreover, apoptosis was induced in mouse brain vascular smooth muscle cells derived from Mut-high-temperature requirement serine peptidase A1 geneL364P mice. In summary, the cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy mouse model described in this study will be beneficial to demonstrate the pathological mechanism of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy and provide new therapeutic targets for clinical treatment.

8.
Plant Physiol ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591151

RESUMO

N6-methyladenosine (m6A) is the most abundant modification of eukaryotic messenger RNA. Although m6A has been demonstrated to affect almost all aspects of RNA metabolism, its global contribution to the post-transcriptional balancing of translational efficiency remains elusive in plants. In this study, we performed a parallel analysis of the transcriptome-wide mRNA m6A distribution and polysome profiling in two maize (Zea mays) inbred lines to assess the global correlation of m6A modification with translational status. m6A sites are widely distributed in thousands of protein-coding genes, confined to a consensus motif and primarily enriched in the 3' untranslated regions, and highly coordinated with alternative polyadenylation usage, suggesting a role of m6A modification in regulating alternative polyadenylation site choice. More importantly, we identified that the m6A modification shows multifaceted correlations with the translational status depending on its strength and genic location. Moreover, we observed a substantial intraspecies variation in m6A modification, and this natural variation was shown to be partly driven by gene-specific expression and alternative splicing. Together, these findings provide an invaluable resource for ascertaining transcripts that are subject to m6A modification in maize and pave the way to a better understanding of natural m6A variation in mediating gene expression regulation.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31566862

RESUMO

The radical-mediated monofluoroalkylative alkynylation of alkenes is disclosed for the first time. The reaction demonstrates a remarkably broad substrate scope in which both activated and unactivated alkenes are suitable materials. Concurrent incorporation of an alkynyl and a monofluoroalkyl groups into alkenes proceeds through the docking-migration sequence, affording a vast array of valuable fluoroalkyl-substituted alkynes. Many complex natural products and drug derivatives are readily functionalized, thus providing an ingenious protocol for the late-stage alkynylation.

10.
J Plast Surg Hand Surg ; : 1-7, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581878

RESUMO

Soft tissue reconstruction of the distal lower leg and foot sole is a challenge for surgeons. In this article, we describe our experience and outcomes with distal lower leg and foot sole reconstruction using the medial plantar flap. From January 2007 to December 2017, 29 consecutive patients from our department underwent reconstruction of soft tissue defects over the distal lower leg, heel and plantar forefoot using medial plantar flaps. Of the 29 patients, the defects were located in the distal lower leg (n = 8 [27.6%]), heel (n = 14 [48.3%]) and plantar forefoot (n = 7 [24.1%]). The mean follow-up period was 18.6 months, 28 (96.6%) survived completely. Lateral partial necrosis occurred in one flap. No patient had recurrence of ulcer and two (6.9%) patients died within 1 year post-reconstruction owing to metastatic malignant melanoma. At last follow-up, all survived patients could walk for more than 1 h in normal shoes. All donor sites were covered with a split-thickness skin graft, no early nor late complications were encountered, and no patients complained about the donor site scar. The medial plantar flap may be considered as an effective method for the repair of small to medium soft tissue defects in the distal lower leg, heel and plantar forefoot.

11.
Int J Sports Med ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593991

RESUMO

Previous cross-sectional studies have reported that higher drop heights do not always result in improved performance, and may increase injury risk during drop jumps (DJ). The purpose of this study was to analyze the kinematics and kinetics during the DJ in order to determine the relative drop height that maximize performance without exposing the lower extremity joints to unnecessary loads. Twenty male Division I college volleyball players volunteered. Data were collected using 11 infrared cameras and two force platforms. Participants performed three maximal effort countermovement jumps (CMJ). Subsequently, 50, 75, 100, 125, and 150% CMJ height (CMJH) was used to scale their relative drop height for three DJ trials per height. There was a significant increase in the landing phase impulse when the drop height exceeded 100%CMJH (p<0.05). At 125% and 150%CMJH, the negative work of knee and ankle significantly increased. The incoming velocity, kinetic energy, landing depth, maximum ground reaction force, landing impulse and power absorption of knee and ankle all increased with drop height (p<0.05). DJ height and reactive strength index following the drop landing were not statistically different between any of the drop heights (p>0.05). 50% to 100%CMJH may be the appropriate individual relative drop height for the DJ.

12.
J Alzheimers Dis ; 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31594231

RESUMO

BACKGROUND: Detecting subtle changes in visual attention from electroencephalography (EEG) and the perspective of eye movement in mild cognitive impairment (MCI) patients can be of great significance in screening early Alzheimer's disease (AD) in a large population at primary care. OBJECTIVE: We proposed an automatic, non-invasive, and quick MCI detection approach based on multimodal physiological signals for clinical decision-marking. METHODS: The proposed model recruited 152 patients with MCI and 184 healthy elderly controls (HC) who underwent EEG and eye movement signal recording under a visual stimuli task, as well as other neuropsychological assessments. Forty features were extracted from EEG and eye movement signals by linear and nonlinear analysis. The features related to MCI were selected by logistic regression analysis. To evaluate the efficacy of this MCI detection approach, we applied the same procedures to achieve the Clinical model, EEG model, Eye movement model, EEG+ Clinical model, Eye movement+ Clinical model, and Combined model, and compared the classification accuracy between the MCI and HC groups with the above six models. RESULTS: After the penalization of logistic regression analysis, five features from EEG and eye movement features exhibited significant differences (p <  0.05). In the classification experiment, the combined model resulted in the best accuracy. The average accuracy for the Clinical/EEG/Eye movement/EEG+ Clinical/Eye movement+ Clinical/Combined model was 68.69%, 61.79%, 73.13%, 69.46%, 75.61%, and 81.51%, respectively. CONCLUSION: These results suggest that the proposed MCI detection tool has the potential to screen MCI patients from HCs and may be a powerful tool for personalized precision MCI screening in the large-scale population under primary care condition.

13.
J Sep Sci ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31508887

RESUMO

The ripened seeds of Strychnos nux-vomica L. have been extensively used as herbal medicines in Asian countries. Dihydroindole-type alkaloids are not only the active constituents but also the toxicants in Strychnos. However, the simultaneous determination of these alkaloids in both crude and processed Semen Strychni is still lacking. The present study represents the first quantitation and relative quantitation assay of 12 dihydroindole-type alkaloids in Strychnos nux-vomica unprocessed and sand-processed seeds using high-performance liquid chromatography coupled with diode array detection and mass spectrometry. The relative concentration of ten alkaloids was calculated by semi-quantification using the internal standard and their amounts in unprocessed and detoxified Semen Strychni were compared. We report here for the first time the significant increase of the two alkaloids, 19-N-methyl-strychnine, and 2,3-dimethoxy-19-N-methyl-strychnine, during the processing of Semen Strychni. Our study provides new insight into the true complexity of seed processing procedure and valuable information for assessing the efficacy and safety for clinical applications of Semen Strychni-containing drugs.

14.
Stem Cell Res Ther ; 10(1): 289, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547878

RESUMO

BACKGROUND: Stem cell-derived pancreatic ß-like cells hold great promise for treating diabetes. Gallbladder belongs to the extrahepatic bile duct system and possesses stem-like cells. These stem cells could be expanded in vitro and have the potential of differentiating into hepatocytes, cholangiocytes, or pancreatic cells. As the gallbladder is highly available, gallbladder stem cells provide a new cell source of pancreatic ß-like cells. In this study, we aimed to investigate an approach for the generation of pancreatic ß-like cells from gallbladder stem cells (GSCs) without genetic modification. METHODS: A CK19CreERT;Rosa26R-GFP mouse was used to isolate CK19+ cells, which represented EpCAM+ stem cells in the gallbladder. They were cultured in the modified Kubota's medium for expansion and further analyzed. Then, we developed a strategy to screen a combination of small molecules that can generate insulin-secreting cells from gallbladder stem cells. These cells were identified with markers of pancreatic cells. Finally, they were seeded into the cellulosic sponge and transplanted to the diabetic mice for functional examination in vivo. RESULTS: Gallbladder stem cells could be expanded for more than 15 passages. They expressed typical hepatic stem cell markers including CK19, EpCAM, Sox9, and albumin. By screening method, we found that adding Noggin, FR180204, and cyclopamine could efficiently induce gallbladder stem cells differentiating into insulin-secreting cells. These cells expressed Pdx1, Nkx6.1, and insulin but were negative for Gcg. After transplantation with the cellulosic sponge, they could ameliorate hyperglycemia in the diabetic mice. CONCLUSION: This study provides a new approach which can generate insulin-secreting cells from the gallbladder without genetic modification. This offers an option for ß cell therapy in treating type 1 diabetes.

15.
Environ Technol ; : 1-8, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31560605

RESUMO

This study was to evaluate the adsorption capability of a magnetic resin (NDMP) to the removal of Congo red (CR) from aqueous solution. The adsorption kinetic and isotherm of NDMP were studied, as well as the desorption performance of NDMP. The results showed that the adsorption process of NDMP on CR was more suitable for Pseudo-second-order kinetic model. The whole adsorption process was affected by intraparticle diffusion and ion exchange. The adsorption isotherm of CR by NDMP was fitted better with Langmuir model. It showed that the adsorption of CR on NDMP resin was single layer adsorption. The maximum adsorption capacity (Qm) of CR at 308 K can reach 354.29 mg/g. In the desorption, 10% NaCl and NaOH eluents had better desorption rate for CR than other mass fraction. While NaCl(10%)-MeOH mixed eluent with volume ratio of 3:7 had the best regeneration performance. The desorption rate can reach 90% within 30 min. The adsorption performance of NDMP on CR didn't decrease after 13 times successive adsorption-desorption by NaCl(10%)-methanol eluent, indicating that NDMP can be efficiently regenerated. The excellent adsorption-desorption performance of NDMP on CR suggests that the magnetic resin has a great potential for treating CR dye wastewater.

16.
Pathol Res Pract ; 215(10): 152606, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31500928

RESUMO

BACKGROUND: Extended from our previously observation that expression of miR-1307 in chemoresistant primary ovarian cancer tissues is elevated, here we are aiming to dissect the function of miR-1307 and its predicted target gene, CIC (capicua transcriptional repressor), in ovarian cancer chemotherapy. METHODS: We evaluated the expression of miR-1307 and CIC in chemoresistant and chemosensitive ovarian cancer tissues and cells by real time-PCR and western blot. We used chemoresistant/chemosensitive cells with miR-1307 suppression/overexpression to study the biological effects of miR-1307 by MTT and flow cytometer. Dual luciferase reporter gene assay was used to validate direct binding between miR-1307 and the 3'-UTR of CIC. Real-time PCR and western blot analyses, MTT and flow cytometry were used to reveal the biological effects of miR-1307 and CIC, as well as their regulation. RESULTS: We found that miR-1307 affects cell cycle dynamics, cell viability in ovarian cancer cells. In addition, its expression level can influence chemosensitivity to paclitaxel in ovarian cancer cells. We also validate that CIC is a downstream target of miR-1307 via its regulation on 3'-UTR of CIC gene and ETV4 and ETV5 are also regulated by miR-1307/CIC axis. CONCLUSIONS: Our data suggested that miR-1307 may be involved in the resistance of ovarian cancer to chemotherapy drugs via regulation of CIC, and should be further explored as a potential therapeutic target.

17.
Arch Oral Biol ; 108: 104537, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31525533

RESUMO

OBJECTIVE: Tobacco smoking is one of the main risk factors for oral squamous cell carcinoma (OSCC) and can induce generation of reactive oxygen species (ROS). In our previous studies, we demonstrated that nicotine, the major ingredient in tobacco, can upregulate an important antioxidant enzyme Peroxiredoxin 1 (Prx1), in oral leukoplakia (OLK), an oral precancerous lesion. The underlying regulatory mechanisms, however, remain unclear. This study aims to identify regulatory mechanisms of nicotine and identify Prx1 interacting proteins in nicotine-associated OLK. DESIGN: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with bioinformatics analysis was conducted to profile Prx1 binding proteins in human dysplastic oral keratinocyte (DOK) cells. Candidate interaction proteins were further verified using Co-immunoprecipitation (Co-IP), Western blot or Duolink assay in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK in mice and human OLK tissues. RESULTS: We identified Thioredoxin (Trx), Nucleolar GTP-binding protein 1 (GTPBP4), GTP-binding protein Di-Ras2 (DIRAS2) and apoptosis signal-regulating kinase 1 (ASK1) as key Prx1 interacting proteins regulated by nicotine. Our data showed that nicotine upregulated Trx, GTPBP4, DIRAS2, and downregulated ASK1 in 4NQO-induced OLK in mice, at least in part dependent on Prx1. The modulations of Trx, GTPBP4, DIRAS2 and ASK1 by nicotine were also found in OLK smokers compared to OLK non-smokers. The in-situ interaction of Trx, GTPBP4, DIRAS2 and ASK1 with Prx1 were validated in human OLK tissues. CONCLUSION: Nicotine may promote OLK development via regulating Prx1 binding proteins Trx, GTPBP4, DIRAS2 and ASK1. The results of this study will help to develop therapeutic approaches for OLK in humans targeting Prx1 interacting protein network.

18.
Mater Sci Eng C Mater Biol Appl ; 105: 109879, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546456

RESUMO

In this study, a porous Ti-alloy based implant with an interconnected channel structure (MAO-CaP-BMP2) is fabricated using a method combining 3D printing, microarc oxidation (MAO) treatment, and co-precipitation of Ca,P layer with BMP-2 technique. The macroporous structure with pore size of 600 µm made by 3D printing not only enhances the ingrowth of cells but also allows the formation of blood vessels inside the implant. As a result, the new bond formation is promoted. In addition, the microporous dioxide layer formed on the implant surface by MAO provides the sites for co-precipitation of Ca,P layer with BMP-2. The microstructure allows the prolonged release of BMP-2. Our results show that a sustained release of BMP-2 over 35 days is achieved for MAO-CaP-BMP2 group longer than Ti without MAO modification group and without Ca,P electrochemical deposition group. The slow release of BMP-2 at the bone/implant interface for a long period of time leads to enhancement of the osseointegration between the implant and surrounding bones. This result indicates that MAO-CaP-BMP2 is a good candidate of growth factor carrier. Successful regeneration of bone requires the concomitant processes of osteogenesis and neovascularization. MAO-CaP-BMP2 modified Ti-alloy implant is both osteoinductive and osteoconductive which can create better osteogenesis and angiogenesis. As a result, it can enhance bone formation.

19.
CNS Neurosci Ther ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549780

RESUMO

AIMS: Insufficient sleep has been found to result in varying degrees of cognitive impairment and emotional changes. Sleep was reported probably responsible for cleaning metabolic wastes in brain by increasing extracellular bulk flow. Herein, we propose that chronic sleep insufficiency in young adult wild-type mice is also linked with dysfunction of intracellular protein degradation pathways and microglia-mediated neuroinflammation, which are potentially important mechanisms in the initiation of neurodegeneration. METHODS: We applied the chronic sleep fragmentation (CSF) model to induce chronic sleep insufficiency in wild-type mice. After 2 months of CSF, cognitive function, amyloid-ß accumulation, dysfunction of endosome-autophagosome-lysosome pathway, and microglia activation were evaluated. RESULTS: Following CSF, impairment of spatial learning and memory, and aggravated anxiety-like behavior in mice were identified by behavioral experiments. Increased intracellular amyloid-ß accumulation was observed in cortex and hippocampus. Mechanistically, CSF could significantly enhance the expression of Rab5 (early endosome marker), Rab7 (late endosome marker), as well as LC3B (autophagosome marker), and autophagy-positive regulatory factors in brain detected by immunofluorescent staining and Western blot. In addition, activation of microglia was evident by enhanced CD68, CD16/32, and CD206 levels after CSF treatment. CONCLUSIONS: Chronic sleep fragmentation could initiate pathogenetic processes similar to the early stage of neurodegeneration, including dysfunction of endosome-autophagosome-lysosome pathway and microglia-mediated neuroinflammation. Our findings further strengthen the link between chronic sleep insufficiency and the initiation of neurodegeneration even if lack of genetic predisposition.

20.
Cell Prolif ; : e12688, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31557368

RESUMO

OBJECTIVES: With age, bone marrow mesenchymal stem cells (BMSC) have reduced ability of differentiating into osteoblasts but have increased ability of differentiating into adipocytes which leads to age-related bone loss. MicroRNAs (miRNAs) play major roles in regulating BMSC differentiation. This paper explored the role of miRNAs in regulating BMSC differentiation swift fate in age-related osteoporosis. MATERIAL AND METHODS: Mice and human BMSC were isolated from bone marrow, whose miR-130a level was measured. The abilities of BMSC differentiate into osteoblast or fat cell under the transfected with agomiR-130a or antagomiR-130a were analysed by the level of ALP, osteocalcin, Runx2, osterix or peroxisome proliferator-activated receptorγ (PPARγ), Fabp4. Related mechanism was verified via qT-PCR, Western blotting (WB) and siRNA transfection. Animal phenotype intravenous injection with agomiR-130a or agomiR-NC was explored by Micro-CT, immunochemistry and calcein double-labelling. RESULTS: MiR-130a was dramatically decreased in BMSC of advanced subjects. Overexpression of miR-130a increased osteogenic differentiation of BMSC and attenuated adipogenic differentiation in BMSC, conversely, Inhibition of miR-130a reduced osteogenic differentiation and facilitated lipid droplet formation. Consistently, overexpression of miR-130a in elderly mice dropped off the bone loss. Furthermore, the protein levels of Smad regulatory factors 2 (Smurf2) and PPARγ were regulated by miR-130a with an negative effect through directly combining the 3'UTR of Smurf2 and PPARγ. CONCLUSIONS: The results indicated that miR-130a promotes osteoblastic differentiation of BMSC by negatively regulating Smurf2 expression and suppresses adipogenic differentiation of BMSC by targeting the PPARγ, and supply a new target for clinical therapy of age-related bone loss.

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