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1.
J Clin Invest ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32365055

RESUMO

De novo lipogenesis is tightly regulated by insulin and nutritional signals to maintain metabolic homeostasis. Excessive lipogenesis induces lipotoxicity, leading to nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Genetic lipogenic programs have been extensively investigated, but epigenetic regulation of lipogenesis is poorly understood. Here, we identified Slug as an important epigenetic regulator of lipogenesis. Hepatic Slug levels were markedly upregulated in mice by either feeding or insulin treatment. In primary hepatocytes, insulin stimulation increased Slug expression, stability, and interactions with epigenetic enzyme lysine-specific demethylase-1 (Lsd1). Slug bound to the fatty acid synthase (Fasn) promoter where Slug-associated Lsd1 catalyzed H3K9 demethylation, thereby stimulating Fasn expression and lipogenesis. Ablation of Slug blunted insulin-stimulated lipogenesis. Conversely, overexpression of Slug, but not a Lsd1 binding-defective Slug mutant, stimulated Fasn expression and lipogenesis. Lsd1 inhibitor treatment also blocked Slug-stimulated lipogenesis. Remarkably, hepatocyte-specific deletion of Slug inhibited the hepatic lipogenic program and protected against obesity-associated NAFLD, insulin resistance, and glucose intolerance in mice. Conversely, liver-restricted overexpression of Slug, but not the Lsd1 binding-defective Slug mutant, had the opposite effects. These results unveil an insulin/Slug/Lsd1/H3K9 demethylation lipogenic pathway that promotes NAFLD and type 2 diabetes.

2.
Hum Cell ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350750

RESUMO

The tumor microenvironment (TM) is an essential factor of tumor progression. Mesenchymal stem cells (MSCs) are important components of the TM and play critical roles in cancer metastasis. Resveratrol (RES) is a potential antitumor drug that has attracted extensive attention. However, it remains unclear whether RES can exert its antitumor activity by targeting MSCs located in the TM. In this study, we demonstrated that the conditioned medium of gastric-cancer-derived MSCs (GC-MSCs) promoted gastric cancer (GC) metastasis and facilitated the progression of epithelialmesenchymal transition (EMT) of GC cells. However, after pretreatment with RES, the prometastatic effect of GC-MSCs on GC cells was reversed. Furthermore, RES reduced GC-MSC (IL-6, IL-8, MCP-1, VEGF) gene expression and protein secretion, and counteracted the activation of the GC-MSC-induced Wnt/ß-catenin signaling of GC cells, with less ß-catenin nuclear transport and declined expression of ß-catenin, CD44, and CyclinD3 in GC cells. Re-expression of ß-catenin impaired the inhibitory effect of RES on GC cells. In conclusion, RES restricted the mobility increase of GC cells and reversed the progress of EMT induced by GC-MSCs by inactivating the Wnt/ß-catenin signaling. GC-MSCs are promising target for RES in the inhibition of GC metastasis.

3.
Dis Markers ; 2020: 6103542, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32377271

RESUMO

Aerobic glycolysis is a hallmark of tumor cells. SGLT1 plays a vital role in glucose metabolism. However, whether SGLT1 could promote cell growth and proliferation in breast cancer remains unclear. Here, we investigated the expression of SGLT1 in breast cancer and examined its role in malignant behavior and prognosis. Further, we examined the SGLT1 expression in breast cancer tissues and its relationship with clinicopathologic characteristics. We clarified that SGLT1 was overexpressed in HER2+ breast cancer cell lines and was affected by HER2 status. We further found that SGLT1 affected breast cancer cell proliferation and patient survival by mediating cell survival pathway activation. SGLT1 was overexpressed in HER2+ breast cancers and associated with lymph node metastasis and HER2+ status. Inhibition of HER2 decreased SGLT1 expression, and the extracellular acidification rate was also reduced in the UACC812 and SKBR3 cell lines. These changes could be reversed by proteasome inhibitor treatment. Knockdown of SGLT1 blocked PI3K/Akt/mTOR signaling, thereby inhibiting cell proliferation. Further, we demonstrated that high SGLT1 was significantly correlated with shorter survival in all breast cancer patients and specifically in HER2+ breast cancer patients. Therefore, we conclude that SGLT1 is overexpressed in HER2+ breast cancer, thereby promoting cell proliferation and shortening survival by activating PI3K/Akt/mTOR signaling. This study submits that SGLT1 is promising not only as a novel biomarker of HER2+ breast cancer subtype but also as a potential drug target.

4.
Nano Lett ; 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32369375

RESUMO

Two-dimensional materials have been widely used in electronics due to their electrical properties that are not accessible in traditional materials. Here, we present the first demonstration of logic functions of unipolar memristors made of functionalized HfSe2-xOx flakes and memtransistors made of MoS2/graphene/HfSe2-xOx van der Waals heterostructures. The two-terminal memristors exhibit stable unipolar switching behavior with high switching ratio (>106), high operating temperature (106 °C), long-term endurance (>104 s), and multibit data storage and can operate as memory latches and logic gates. Benefiting from these superior memristive properties, the three-terminal heterostructure memtransistors show wide tunability in electrical switching behaviors, which can simultaneously implement logic operation and data storage. Finally, we investigate their application prospect in logical units with memory capability, such as D-type flip-flop. These results demonstrate the potential of two-dimensional materials for resistive switching applications and open up an avenue for future in-memory computing.

5.
Oncol Rep ; 43(6): 2017-2027, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32323833

RESUMO

Tamoxifen is widely used as a highly effective drug for treating estrogen­receptor (ER) alpha­positive breast cancer. However, tamoxifen resistance developed during cancer treatment remains a significant challenge. Tongue cancer resistance­related protein1 (TCRP1), which is recognized as a novel drug target, is related to chemo­resistance in human cancers, moreover, it is often overexpressed in various cancer cells, such as in lung cancer, breast cancer, and tongue cancer. However, the effects of TCRP1 on tamoxifen­resistant breast cancer cells and tissues are far from clear. The present study revealed that TCRP1 induced tamoxifen resistance in breast cancer cells. Western blotting, quantitative real­time polymerase chain reaction (RT­PCR) and immunohistochemical staining were performed to detect the expression level of TCRP1 in vivo and in vitro between primary breast cancer tissues and tamoxifen­resistant breast cancer tissues. The data revealed that the expression of TCRP1 was upregulated in the tamoxifen­resistant breast cancer tissues and human breast cancer cell line, MCF­7. Further study revealed that knocking down TCRP1 inhibited the growth of MCF­7 cells with tamoxifen­resistance (MCF7­R cells) and induced cell apoptosis. Moreover, TCRP1 promoted serum­ and glucocorticoid­inducible kinase 1 (SGK1) activation via phosphorylation of phosphoinositide­dependent kinase 1 (PDK1) in MCF7­R cells. In addition, it was also observed that knocking down TCRP1 inhibited tumorigenesis of MCF­7 cells in nude mice. In conclusion, these data indicated that TCRP1 could induce tamoxifen resistance by regulating the PDK1/SGK1 signaling pathway. Thus, TCRP1 could be explored as a promising candidate for treating tamoxifen­resistant breast cancer in the future.

6.
Epigenetics ; : 1-18, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32303148

RESUMO

The epitranscriptomic writer Alkylation Repair Homolog 8 (ALKBH8) is a transfer RNA (tRNA) methyltransferase that modifies the wobble uridine of selenocysteine tRNA to promote the specialized translation of selenoproteins. Using Alkbh8 deficient (Alkbh8def) mice, we have investigated the importance of epitranscriptomic systems in the response to naphthalene, an abundant polycyclic aromatic hydrocarbon and environmental toxicant. We performed basal lung analysis and naphthalene exposure studies using wild type (WT), Alkbh8def and Cyp2abfgs-null mice, the latter of which lack the cytochrome P450 enzymes required for naphthalene bioactivation. Under basal conditions, lungs from Alkbh8def mice have increased markers of oxidative stress and decreased thioredoxin reductase protein levels, and have reprogrammed gene expression to differentially regulate stress response transcripts. Alkbh8def mice are more sensitive to naphthalene induced death than WT, showing higher susceptibility to lung damage at the cellular and molecular levels. Further, WT mice develop a tolerance to naphthalene after 3 days, defined as resistance to a high challenging dose after repeated exposures, which is absent in Alkbh8def mice. We conclude that the epitranscriptomic writer ALKBH8 plays a protective role against naphthalene-induced lung dysfunction and promotes naphthalene tolerance. Our work provides an early example of how epitranscriptomic systems can regulate the response to environmental stress in vivo.

7.
J Pharm Pharmacol ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32346882

RESUMO

OBJECTIVE: The purpose of this study is to reveal the pharmacokinetic profiles of astilbin with various doses in rats and investigate the oral absolute bioavailability and tissue distribution of astilbin after oral administration. METHODS: Wistar rats were orally administered astilbin 12, 24 mg/kg and intravenous administered astilbin 6 mg/kg randomly. The concentration of astilbin in rat plasma and various tissue samples was determined by LC-MS/MS method. Noncompartmental pharmacokinetic parameters including AUC and t1/2 were calculated from plasma concentration-time data of astilbin with the DAS 3.0. KEY FINDINGS: After oral administration of astilbin 12 and 24 mg/kg to rats, the oral absolute bioavailability of astilbin were 1.16 ± 0.695% and 1.27 ± 0.379%; the plasma elimination half-lives (t1/2 ) were 101 ± 35.8 and 109 ± 25.3 min, respectively. Astilbin had a rapid absorption and a wide distribution throughout the whole body except liver and fat following oral administration. Astilbin could penetrate the blood-brain barrier of rat. CONCLUSIONS: The oral absolute bioavailability of astilbin is poor because of the low permeability and solubility. Both oral absorption and clearance of astilbin in rats are rapid after oral administration.

8.
Sci Rep ; 10(1): 6568, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32300186

RESUMO

The function and susceptibility of various drugs are tested with renal proximal tubular epithelial cells; yet, replicating the morphology and kidneys function using the currently available in vitro models remains difficult. To overcome this difficulty, in the study presented in this paper, a device and a three-layer microfluidic chip were developed, which provides a simulated environment for kidney organs. This device includes two parts: (1) microfluidic drug concentration gradient generator and (2) a flow-temperature controlled platform for culturing of kidney cells. In chip study, renal proximal tubular epithelial cells (RPTECs) and peritubular capillary endothelial cells (PCECs) were screened with the drugs to assess the drug-induced nephrotoxicity. Unlike cells cultured in petri dishes, cells cultured in the microfluidic device exhibited higher performance in terms of both cell growth and drug nephrotoxicity evaluation. It is worth mentioning that a significant decrease in cisplatin-induced nephrotoxicity was found because of the intervention of cimetidine in the microfluidic device. In conclusion, the different in the cell performance between the microfluidic device and the petri dishes demonstrates the physiological relevance of the nephrotoxicity screening technology along with the microfluidic device developed in this study. Furthermore, this technology can also facilitate the development of reliable kidney drugs and serve as a useful and efficient test-bed for further investigation of the drug nephrotoxicity evaluation.

9.
Minerva Urol Nefrol ; 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32284528

RESUMO

BACKGROUND: Concerns have been raised in regard to the management of bladder cuff with these minimally invasive approaches. This study is to describe a modified radical nephroureterectomy (RNU) with pure retroperitoneoscopic extravesical standardized seeable (PRESS) bladder cuff excision (BCE) and to assess its outcomes based on a novel concept of intraoperative "trifecta". METHODS: Twenty-four patients with upper urinary tract urothelial carcinoma underwent retroperitoneoscopic RNU from Aug 2017 to Aug 2019. A modified RNU with PRESS BCE and lymph node dissection (LND) was performed. Descriptive analysis of patients' characteristics, surgical technique, perioperative outcomes, and follow-up data was performed. BCE trifecta was defined as en bloc excision, mucosa- to-mucosa reliable closure and no urine spillage. RESULTS: In 23 out of 24 cases (95.8%) the procedure was successfully completed. One patient was converted to open distal ureterectomy with a Gibson incision due to peritoneum rupture during dissection of the distal ureter. BCE trifecta was achieved in 95.7% (22/23) cases of all patients finished with PRESS technique. Median OT was 260 min (IQR: 220-305) with median EBL of 100 ml (IQR: 100-250). Median OT for distal ureterectomy was 52 min (IQR: 40-69). No positive surgical margin occurred. Median postoperative hospital stay was 6 d (IQR: 5-7). Median follow-up time was 7 mo (IQR: 5-17). One patient (4.3%) experienced bladder recurrence and no patient developed distant metastasis or died of the disease. CONCLUSIONS: Herein, we demonstrate a standardized retroperitoneoscopic RNU technique that is safe and reproducible, enabling the visual confirmation of complete BCE and facilitating LND. BCE trifecta should be a routine goal in minimally invasive RNU. Prospective comparison with the standard open surgical technique is warranted.

10.
Metabolism ; 107: 154222, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32246987

RESUMO

Fructose over-consumption contributes to the development of liver steatosis in part by stimulating ChREBPα-driven de novo lipogenesis. However, the mechanisms by which fructose activates ChREBP pathway remain largely undefined. Here we performed affinity purification of ChREBPα followed by mass spectrometry and identified DDB1 as a novel interaction protein of ChREBPα in the presence of fructose. Depletion and overexpression of Ddb1 showed opposite effects on the ChREBPα stability in hepatocytes. We next tested the impact of hepatic Ddb1 deficiency on the fructose-induced ChREBP pathway. After 3-week high-fructose diet feeding, both Ddb1 liver-specific knockout and AAV-TBG-Cre-injected Ddb1flox/flox mice showed significantly reduced ChREBPα, lipogenic enzymes, as well as triglycerides in the liver. Mechanistically, DDB1 stabilizes ChREBPα through CRY1, a known ubiquitination target of DDB1 E3 ligase. Finally, overexpression of a degradation-resistant CRY1 mutant (CRY1-585KA) reduces ChREBPα and its target genes in the mouse liver following high-fructose diet feeding. Our data revealed DDB1 as an intracellular sensor of fructose intake to promote hepatic de novo lipogenesis and liver steatosis by stabilizing ChREBPα in a CRY1-dependent manner.

11.
J Org Chem ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32255650

RESUMO

A new type of 1-unsymmetrical D-A cyclopropanes containing a cyclic enone motif was obtained by the desymmetrization of 1-symmetrical D-A cyclopropanes via first the Lewis acid-catalyzed O-nucleophilic ring-opening reaction with 1,3-cyclodiones followed by an organobase-promoted unexpected multistep intramolecular transformation.

12.
Mater Sci Eng C Mater Biol Appl ; 111: 110836, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279765

RESUMO

Solid dispersion is a widely used method to improve the dissolution and oral bioavailability of water-insoluble drugs. However, due to the strong hydrophobicity, the drug crystallization in the release media after drug dissolution and the resulted decreased drug absorption retards the use of solid dispersions. It is widely known that the amphiphilic copolymer can encapsulate the hydrophobic compounds and help form stable nano-dispersions in water. Inspired by this, we tried to formulate the solid dispersion of nimodipine by using amphipathic copolymer as one of the carriers. Concerning the solid dispersions, there are many important points involved in these formulations, such as the miscibility between the drug and the carriers, the storage stability of solid dispersions, the dissolution enhancement and so on. In this study, a systemic method is proposed. In details, the supersaturation test and the glass transition temperature (Tg) measurement to predict the crystallization inhibition, the ratios of different components and the storage stability, the interactions among the components were investigated in detail by nuclear magnetic resonance (1H NMR) and isothermal titration calorimetry (ITC) and, the final dissolution and oral bioavailability enhancement. It was found that the amphiphilic copolymer used in the solid dispersion encouraged the formation the drug loading micelles in the release media and, finally, the problem of drug crystallization in the dissolution process was successfully solved.

13.
Hereditas ; 157(1): 11, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264962

RESUMO

BACKGROUND: Inflammation is one of the factors associated with prostate cancer. The cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in inflammation. Several studies have focused on the association between TNF-α polymorphisms and prostate cancer development. Our meta-analysis aimed to estimate the association between TNF-α rs1800629 (- 308 G/A), rs361525 (- 238 G/A) and rs1799724 polymorphisms and prostate cancer risk. METHODS: Eligible studies were identified from electronic databases (PubMed, Embase, Wanfang and CNKI) using keywords: TNF-α, polymorphism, prostate cancer, until Nov 15, 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to determine the association from a quantitative point-of-view. Publication bias and sensitivity analysis were also applied to evaluate the power of current study. All statistical analyses were done with Stata 11.0 software. RESULTS: Twenty-two different articles were included (22 studies about rs1800629; 8 studies for rs361525 and 5 studies related to rs1799724). Overall, no significant association was found between rs1800629 and rs1799724 polymorphisms and the risk of prostate cancer in the whole (such as: OR = 1.03, 95% CI = 0.92-1.16, P = 0.580 in the allele for rs1800629; OR = 0.95, 95% CI = 0.84-1.07, P = 0.381 in the allele for rs1799724). The rs361525 polymorphism also had no association with prostate cancer in the cases (OR = 0.93, 95% CI = 0.66-1.32, P = 0.684 in the allele) and ethnicity subgroup. The stratified subgroup of genotype method, however, revealed that the rs361525 variant significantly decreased the risk of prostate cancer in the Others (OR = 0.65, 95% CI = 0.47-0.89, P = 0.008, A-allele vs G-allele) and PCR-RFLP (OR = 2.68, 95% CI = 1.00-7.20, P = 0.050, AG vs GG or AA+AG vs GG) methods. CONCLUSIONS: In summary, the findings of the current meta-analysis indicate that the TNF-α rs1800629, rs361525 and rs1799724 polymorphisms are not correlated with prostate cancer development, although there were some pooled positive results. Further well-designed studies are necessary to form more precise conclusions.

14.
Am J Emerg Med ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32327248

RESUMO

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-pro BNP) increases in patients with heart failure and renal failure. Hemodialysis is a useful treatment to these patients. The aim of this study was to conduct a systematic and meta-analysis to evaluate the influence of hemodialysis on NT-pro BNP concentration. METHODS: Relevant studies were identified by searching in PubMed, Medline, Embase, OVID, Web of Science, China Biology Medicine (CBM) and Google Scholar. Standard errors of mean difference along with its 95% CI were calculated to assess the association of hemodialysis and NT-pro BNP concentration. Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored. RESULTS: Individual patient data was obtained from 270 participants in seven articles suffered from chronic renal failure with regular hemodialysis, which was standard normal distribution. A fixed effects model suggested a pooled mean difference of 79.265 (95% CI: -331.172-489.702) without heterogeneity (Q = 0.70 df = 6 p = 0.994 I2 = 0.0%). The adults group estimated a MD of 209.958 (95% CI: -3080.76-3500.67; p = 0.900) with no heterogeneity (Q = 0.70 df = 4 p = 0.983 I2 = 0.0%). In the four articles whose data were not standard normal distribution, hemodiafiltration protocols were similar; three articles reported increasing and one decreasing in NT-proBNP concentration. CONCLUSIONS: Finding of this systematic review and meta-analysis demonstrated that NT-pro BNP may not been influenced by hemodialysis, and it could not been used to determine if heart failure is improving in patients with renal failure who are treated with hemodialysis.

15.
Dalton Trans ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32348385

RESUMO

The 1,2-diaza-4-phospholide (dp-) dipotassium ate complexes of chromium(ii) {[(η1-N-3,5-tBu2dp)4Cr][(η5-(N,N,C,C,P))2-K(η1-O-THF)2]2} (5) and {[(η1-N-3,5-Ph2dp)4Cr][(η5-(N,N,C,C,P))2-K(η1-O-THF)2]2}∞ (6) were synthesized and characterized by X-ray single crystal structure analysis. Complex 5 with a near-square planar geometry at the chromium(ii) ion was unambiguously characterized by the high field electron paramagnetic resonance (HF-EPR) technique and magnetic measurements, revealing that it is a field-induced single-molecule magnet (SMM).

16.
Nano Lett ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32338924

RESUMO

The manipulation of magnetism provides a unique opportunity for the development of data storage and spintronic applications. Until now, electrical control, pressure tuning, stacking structure dependence, and nanoscale engineering have been realized. However, as the dimensions are decreased, the decrease of the ferromagnetism phase transition temperature (Tc) is a universal trend in ferromagnets. Here, we make a breakthrough to realize the synthesis of 1 and 2 unit cell (UC) Cr2Te3 and discover a room-temperature ferromagnetism in two-dimensional Cr2Te3. The newly observed Tc increases strongly from 160 K in the thick flake (40.3 nm) to 280 K in 6 UC Cr2Te3 (7.1 nm). The magnetization and anomalous Hall effect measurements provided unambiguous evidence for the existence of spontaneous magnetization at room temperature. The theoretical model revealed that the reconstruction of Cr2Te3 could result in anomalous thickness-dependent Tc. This dimension tuning method opens up a new avenue for manipulation of ferromagnetism.

17.
J Am Chem Soc ; 142(20): 9203-9209, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32330022

RESUMO

CpG methylation of DNA is common in mammalian cells. In sperm, the DNA has the highest level of CpG methylation and is condensed into toroidal structures. How CpG methylation affects DNA structures and interactions is important to understand its biological roles but is largely unknown. Using an RNA-DNA-RNA structure, we observed the equilibrium hopping dynamics between the condensed and extended states of DNA in the presence of polyamines or polylysine peptide as a reduced model of histone tails. Combing with the measured DNA elasticities, we report that CpG methylation of each cytosine nucleotide substantially increases DNA-DNA attraction by up to 0.2 kBT. For the DNA with 57% GC content, the relative increase caused by CpG methylation is up to 32% for the spermine-induced DNA-DNA attraction and up to 9% for the polylysine-induced DNA-DNA attraction. These findings help us to evaluate the energetic contributions of CpG methylation in sperm development and chromatin regulation.

18.
Clin Immunol ; 214: 108387, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32194234

RESUMO

Biallelic variants in BLNK cause primary B-cell immunodeficiency that usually results in absence of B cells and immunoglobulin. Here, we identified disease-causing variant(s) in two unrelated Chinese patients with agammaglobulinemia. Patient 1 showed a moderate reduction in total B-cell count but demonstrated both extremely low levels of memory B-cells and lower levels of memory T cells relative to those in healthy controls. Whole-exome sequencing (WES) revealed a novel heterozygous splice variant (c.676+1G>A), and suggested exon 9 deletion from BLNK, which was subsequently validated by quantitative polymerase chain reaction. For Patient 2, WES revealed novel compound heterozygous of a frameshift variant (p.T152Pfs*6) and a synonymous variant (c.525G>A) that resulted in exon 6 skipping, according to cDNA sequencing. These findings represent the first report of a BLNK-deficient patient presenting with impaired memory B-cell and memory T-cell development. Furthermore, this study is the first reporting a pathogenic synonymous splice variant in BLNK.

19.
FASEB J ; 34(5): 6038-6054, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32202355

RESUMO

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF-1α pathway were determined by measuring expression of VEGF, EGF, HIF-1α, and HSP-90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF-1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α-SMA in skin tissues, and reduced TNF-α, IL-1ß, and IL-6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF-1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF-1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF-1α pathway.

20.
Nano Lett ; 20(5): 3378-3387, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32212734

RESUMO

Optoelectronic synaptic devices have been attracting increasing attention due to their critical role in the development of neuromorphic computing based on optoelectronic integration. Here we start with silicon nanomembrane (Si NM) to fabricate optoelectronic synaptic devices. Organolead halide perovskite (MAPbI3) is exploited to form a hybrid structure with Si NM. We demonstrate that synaptic transistors based on the hybrid structure are very sensitive to optical stimulation with low energy consumption. Synaptic functionalities such as excitatory post-synaptic current (EPSC), paired-pulse facilitation, and transition from short-term memory to long-term memory (LTM) are all successfully mimicked by using these optically stimulated synaptic transistors. The backgate-enabled tunability of the EPSC of these devices further leads to the LTM-based mimicking of visual learning and memory processes under different mood states. This work contributes to the development of Si-based optoelectronic synaptic devices for neuromorphic computing.

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