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1.
Chem Commun (Camb) ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633013

RESUMO

A novel chromium(VI)-based compound, [(CH3CH2)3N(CH2Cl)][CrO3Cl] (1), undergoes a high-temperature phase transition at around 340.9 K, accompanied by an ultra-large entropy change of 63.49 J mol-1 K-1. Compound 1 exhibits a moderate ferroelectric polarization of 0.48 µC cm-2 and a remarkable CD signal. Strikingly, 1 occupies a narrow band gap of 2.22 eV, which is chiefly attributed to the inorganic [CrO3Cl]- tetrahedron. It is believed that these findings will contribute to an alternative pathway for the design of multifunctional ferroelectric materials, whose potential applications will be in semiconductors, energy storage, etc.

2.
Transl Neurodegener ; 10(1): 39, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34657636

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disorder that primarily affects the elderly. While the etiology of PD is likely multifactorial with the involvement of genetic, environmental, aging and other factors, α-synuclein (α-syn) pathology is a pivotal mechanism underlying the development of PD. In recent years, astrocytes have attracted considerable attention in the field. Although astrocytes perform a variety of physiological functions in the brain, they are pivotal mediators of α-syn toxicity since they internalize α-syn released from damaged neurons, and this triggers an inflammatory response, protein degradation dysfunction, mitochondrial dysfunction and endoplasmic reticulum stress. Astrocytes are indispensable coordinators in the background of several genetic mutations, including PARK7, GBA1, LRRK2, ATP13A2, PINK1, PRKN and PLA2G6. As the most abundant glial cells in the brain, functional astrocytes can be replenished and even converted to functional neurons. In this review, we discuss astrocyte dysfunction in PD with an emphasis on α-syn toxicity and genetic modulation and conclude that astrocyte replenishment is a valuable therapeutic approach in PD.

3.
Immunity ; 54(10): 2218-2230.e5, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34644557

RESUMO

The RNA sensor MDA5 recruits the signaling adaptor MAVS to initiate type I interferon signaling and downstream antiviral responses, a process that requires K63-linked polyubiquitin chains. Here, we examined the mechanisms whereby K63-polyUb chain regulate MDA5 activation. Only long unanchored K63-polyUbn (n ≥ 8) could mediate tetramerization of the caspase activation and recruitment domains of MDA5 (MDA5CARDs). Cryoelectron microscopy structures of a polyUb13-bound MDA5CARDs tetramer and a polyUb11-bound MDA5CARDs-MAVSCARD assembly revealed a tower-like formation, wherein eight Ubs tethered along the outer rim of the helical shell, bridging MDA5CARDs and MAVSCARD tetramers into proximity. ATP binding and hydrolysis promoted the stabilization of RNA-bound MDA5 prior to MAVS activation via allosteric effects on CARDs-polyUb complex. Abundant ATP prevented basal activation of apo MDA5. Our findings reveal the ordered assembly of a MDA5 signaling complex competent to recruit and activate MAVS and highlight differences with RIG-I in terms of CARD orientation and Ub sensing that suggest different abilities to induce antiviral responses.

4.
Pak J Pharm Sci ; 34(3): 875-882, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602409

RESUMO

For many patients with refractory epilepsy, antiepileptic drugs (AEDs) cannot reach effective therapeutic concentration in brain due to drugtolerance. In order to increase the selectivity of lamotrigine in brain, lamotrigine loaded nano-liposomes (LTG-NL) were designed, prepared, and the physio-chemical characterizations were observed. The distribution of LTG-NL in mice was studied by detecting the concentration of LTG extracted from animal organs, then targeting efficiency (TE) and targeting index (TI) were calculated to evaluate the brain targeting effect of LTG-NL. The mechanism of LTG-NL entry into cell was determined by A549 cell internalization experiments. The results showed that LTG-NL were small and uniform spherical particles with high entrapment efficiency and release. In vivo distribution study showed brain selectivity of LTG-NL, and TE and TI values further demonstrated the targeting capacity of LTG-NL. The cell internalization of LTG-NL was mainly by the pathway of clathrin-mediated endocytosis and macropinocytosis. These findings suggested this lipid formulation would be a drug delivery system for insoluble drugs to promote drug release and enhance brain selectivity.

5.
Chemistry ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34498317

RESUMO

The multifunctional two-dimensional (2D) organic-inorganic hybrid perovskites have potential applications in many fields, such as, semiconductor, energy storage and fluorescent device etc. Here, a 2D Ruddlesden-Popper (RP) perovskite (IPA)2 (FA)Pb2 I7 (1, IPA+ =C3 H9 NI+ , FA+ =CN2 H5 + ) is determined for its photophysical properties. Strikingly, 1 reveals a solid reversible phase transition with Tc of 382 K accompanied by giant entropy change of 40 J mol-1 K-1 . Further optical investigations indicate that 1 reveals a narrow direct bandgap (2.024 eV) attributed to the slight bending of I-Pb-I edge and inorganic [Pb2 I7 ]n layer and a superior photoluminescence (PL) emission with super long lifetime of 0.1607 ms. It is believed that this work will pave an avenue to further design multifunctional semiconductors that combines energy storage and photoelectric materials.

6.
Biomolecules ; 11(9)2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34572500

RESUMO

As a pathological biomarker of Parkinson's disease, α-synuclein is thought to be a prion-like protein, but evidence for the transmission of α-synuclein from blood to the brain is unclear. The goals of this study were to determine whether blood-derived α-synuclein could enter the brains of mice and whether α-synuclein in the brain could be cleared by parabiosis. Heterochronic parabiosis was performed on SNCAA53T transgenic mice (A53T mice) and wildtype mice. The levels of human α-synuclein in the blood and substantia nigra of wildtype mice were significantly increased after 4-month parabiosis with A53T mice. Moreover, the expression of α-synuclein filament, but not of total α-synuclein, was significantly increased in the substantia nigra of wildtype mice that were paired with A53T mice. However, the levels of human α-synuclein displayed no significant change in the serum, blood, or substantia nigra of A53T mice. These results provide direct evidence that pathological α-synuclein can be transmitted from blood to the brain in the heterochronic parabiosis system; however, it appears to be difficult to clear it from the brain in a short period of time.

7.
Chem Asian J ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519418

RESUMO

Bistable switches (electrical switching between "ON" and "OFF" bistable states) have gradually developed into an ideal category of highly intelligent materials, due to their significant applications in optical technology, signal processors, data storage and other switchable media applications in the field of electrical devices. Here, we successfully designed and synthesized [(FC6 H4 C2 H4 NH3 )2 MCl4 ]n (FC6 H4 C2 H4 NH3 + )=deprotonated 4-fluoro- phenethylamine; M=Cd (1), Mn (2)), which realized the coupling of thermo-dielectric switching characteristics, semi-conductor characteristics and photo-luminescent properties. DSC (differential scanning calorimetry) and dielectric measurements show that 1 is a sensitive dielectric bistable switch between the high dielectric (ON) and low dielectric (OFF) states. The temperature-variable single crystal structure shows that the both 1 and 2 undergo a high-temperature reversible phase transition around 383 K/380 K, which is caused by the order-disordered transformation of organic cations and the slight distortion of the inorganic framework. In particular, 1 shows outstanding switchable dielectric behavior and semiconducting properties. Further, 1 and 2 emit strong green and yellow luminescence at 527 and 595 nm, respectively.

8.
Cereb Cortex ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546353

RESUMO

Soma spacing and dendritic arborization during brain development are key events for the establishment of proper neural circuitry and function. Transcription factor Satb2 is a molecular node in regulating the development of the cerebral cortex, as shown by the facts that Satb2 is required for the regionalization of retrosplenial cortex, the determination of callosal neuron fate, and the regulation of soma spacing and dendritic self-avoidance of cortical pyramidal neurons. In this study, we explored downstream effectors that mediate the Satb2-implicated soma spacing and dendritic self-avoidance. First, RNA-seq analysis of the cortex revealed differentially expressed genes between control and Satb2 CKO mice. Among them, EphA7 transcription was dramatically increased in layers II/III of Satb2 CKO cortex. Overexpression of EphA7 in the late-born cortical neurons of wild-type mice via in utero electroporation resulted in soma clumping and impaired self-avoidance of affected pyramidal neurons, which resembles the phenotypes caused by knockdown of Satb2 expression. Importantly, the phenotypes by Satb2 knockdown was rescued by reducing EphA7 expression in the cortex. Finally, ChIP and luciferase reporter assays indicated a direct suppression of EphA7 expression by Satb2. These findings provide new insights into the complexity of transcriptional regulation of the morphogenesis of cerebral cortex.

9.
J Med Chem ; 64(19): 14647-14663, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477384

RESUMO

CDK9 is an essential drug target correlated to the development of acute myeloid leukemia (AML). Starting from the hit compound 10, which was discovered through a screening of our in-house compound library, the structural modifications were carried out based on the bioisosterism and scaffold hopping strategies. Consequently, compound 37 displayed the optimal CDK9 inhibitory activity with an IC50 value of 5.41 nM, which was nearly 1500-fold higher than compound 10. In addition, compound 37 exhibited significant antiproliferative activity in broad cancer cell lines. Further investigation of in vivo properties demonstrated that compound 37 could be orally administrated with an acceptable bioavailability (F = 33.7%). In MV-4-11 subcutaneous xenograft mouse model, compound 37 (7.5 mg/kg) could significantly suppress the tumor progression with a T/C value of 27.80%. Compound 37 represents a promising lead compound for the development of a novel class of CDK9 inhibitors for the treatment of acute myeloid leukemia.

10.
Small ; : e2103744, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553488

RESUMO

Lithium-sulfur battery (LSB) is regarded as a preferential option for next-generation energy-storage system, but the lithium polysulfides (LiPSs) shuttling effect and the uncontrollable growth of dendritic Li in the anode impede its commercial viability. To address both of the issues simultaneously, a well-designed hybrid of MgO ultrafine nanocrystals dispersed on graphene-supported carbon nanosheets (MCG) is developed via a facile self-template strategy as dual-functional host for both sulfur and lithium. Relying on the coordination of strong LiPS-capturing capability, the shuttling effect is inhibited. Furthermore, the lithiophilic configuration with high specific surface area induce homogenous Li deposition, thus preventing the formation of disordered lithium dendrite. Integrating all these advantages, a full cell based on S@MCG cathode and Li@MCG@Cu anode exhibits a stable capacity at 0.5 C for 150 cycles with a low capacity fading rate. Furthermore, the full cell achieves a high capacity retention of 85.5% at a high S areal loading of 3.82 mg cm-2 under the condition of a low electrolyte/sulfur ratio (E/S) of 6.5 µL mg-1 and negative/positive capacity ratio (N/P) of 3. This strategy satisfying both cathode and anode host provides a viable approach to realize high-energy-density and dendrite-free LSBs.

11.
Cell Death Dis ; 12(10): 879, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34564702

RESUMO

Dopaminergic (DA) neurons in the arcuate nucleus (ARC) of the hypothalamus play essential roles in the secretion of prolactin and the regulation of energy homeostasis. However, the gene regulatory network responsible for the development of the DA neurons remains poorly understood. Here we report that the transcription factor special AT-rich binding protein 2 (Satb2) is required for the development of ARC DA neurons. Satb2 is expressed in a large proportion of DA neurons without colocalization with proopiomelanocortin (POMC), orexigenic agouti-related peptide (AgRP), neuropeptide-Y (NPY), somatostatin (Sst), growth hormone-releasing hormone (GHRH), or galanin in the ARC. Nestin-Cre;Satb2flox/flox (Satb2 CKO) mice show a reduced number of ARC DA neurons with unchanged numbers of the other types of ARC neurons, and exhibit an increase of serum prolactin level and an elevated metabolic rate. The reduction of ARC DA neurons in the CKO mice is observed at an embryonic stage and Dlx1 is identified as a potential downstream gene of Satb2 in regulating the development of ARC DA neurons. Together, our study demonstrates that Satb2 plays a critical role in the gene regulatory network directing the development of DA neurons in ARC.

12.
J Med Chem ; 64(19): 14822-14847, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34538051

RESUMO

Triple-negative breast cancer (TNBC) is highly aggressive with very limited treatment options due to the lack of efficient targeted therapies and thus still remains clinically challenging. Targeting transcription-associated cyclin-dependent kinases to remodel transcriptional regulation shows great promise in cancer therapy. Herein, we report the synthesis, optimization, and evaluation of new series of heterobifunctional molecules as highly selective and efficacious CDK9 degraders, enabling potent inhibition of TNBC cell growth and rapidly targeted degradation of CDK9. Moreover, the most potent CDK9 degrader (compound 45) induces cell apoptosis in vitro and inhibits tumor growth in the MDA-MB-231 TNBC model. Furthermore, the RNA-seq, immunohistochemistry assays demonstrate that the CDK9 degrader downregulates the downstream targets, such as MYC, at the transcriptional level, resulting apoptosis in TNBC cells. Our work establishes that 45 is a highly potent and efficacious CDK9 degrader for targeting transcription regulation, which represents an effective strategy and great potential as a new targeted therapy for TNBC.

13.
J Genet Genomics ; 48(8): 671-680, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417123

RESUMO

DNA sequencing is vital for many aspects of biological research and diagnostics. Despite the development of second and third generation sequencing technologies, Sanger sequencing has long been the only choice when required to precisely track each sequenced plasmids or DNA fragments. Here, we report a complete set of novel barcoding and assembling system, Highly-parallel Indexed Tagmentation-reads Assembled Consensus sequencing (HITAC-seq), that could massively sequence and track the identities of each individual sequencing sample. With the cost of much less than that of single read of Sanger sequencing, HITAC-seq can generate high-quality contiguous sequences of up to 10 kilobases or longer. The capability of HITAC-seq was confirmed through large-scale sequencing of thousands of plasmid clones and hundreds of amplicon fragments using approximately 100 pg of input DNAs. Due to its long synthetic length, HITAC-seq was effective in detecting relatively large structural variations, as demonstrated by the identification of a ∼1.3 kb Copia retrotransposon insertion in the upstream of a likely maize domestication gene. Besides being a practical alternative to traditional Sanger sequencing, HITAC-seq is suitable for many high-throughput sequencing and genotyping applications.

14.
Asian J Androl ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34396994

RESUMO

Experimental autoimmune prostatitis (EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus (PVN). However, the mechanism has not yet been elucidated. Herein, we screened out the target prostate-derived inflammation cytokines (PDICs) by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid (CSF) between EAP rats and their controls. After identifying the target PDIC, qualified males in initial copulatory behavior testing (CBT) were subjected to implanting tubes onto bilateral PVN. Next, they were randomly divided into four subgroups (EAP-1, EAP-2, Control-1, and Control-2). After 1-week recovery, EAP-1 rats were microinjected with the target PDIC inhibitor, Control-1 rats were microinjected with the target PDIC, while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF (aCSF). Results showed that only interleukin-1ß(IL-1ß) had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls (P < 0.001) and significantly higher protein concentrations in both the serum (P = 0.001) and CSF (P < 0.001) of the EAP groups compared to the Control groups. Therefore, IL-1ß was identified as the target PDIC which crosses the blood-brain barrier, thereby influencing the central nervous system. Moreover, the EAP-1 subgroup displayed a gradually prolonged ejaculation latency (EL) in the last three CBTs (all P < 0.01) and a significantly lower expression of NMDA NR1 subunit in the PVN (P = 0.043) compared to the respective control groups after a 10-day central administration of IL-1ß inhibitors. However, the Control-1 subgroup showed a gradually shortened EL (P < 0.01) and a significantly higher NR1 expression (P = 0.004) after homochronous IL-1ß administration. Therefore, we identified IL-1ß as the primary PDIC which shortens EL in EAP rats. However, further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1ß upregulates NMDA expression.

15.
Front Chem ; 9: 732378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414165

RESUMO

Perfluorocarboxylic acids (PFCAs) are an emerging class of persistent organic pollutants. During the fabrication process, it is unavoidable to form PFCA homologs or isomers which exhibit distinct occurrence, bioaccumulation, and toxicity. The precision measurement of PFCAs is therefore of significant importance. However, the existing characterization techniques, such as LC-MS/MS, cannot fully meet the requirement of isomer-specific analysis, largely due to the lack of authentic standards. Single-molecule sensors (SMSs) based on nanopore electrochemistry may be a feasible solution for PFCAs determination, thanks to their ultra-high spatiotemporal resolutions. Hence, as a first step, this work was to elucidate the influence of electrolyte concentration on the four most critical indicators of nanopore measurements, and furthermore, performance of nanopore SMSs. More specifically, three of the most representative short-chain PFCAs, perfluoropentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA) and perfluoroheptanoic acid (PFHpA), were adopted as the target analytes, aerolysin nanopore was employed as the sensing interface, and 2, 3 and 4 M KCl solutions were used as electrolytes. It was found that, when the concentration of KCl solution increased from 2 to 4 M, the conductance of aerolysin nanopore increased almost linearly at a rate of 0.5 nS per molar KCl within the whole voltage range, the current blockade of PFPeA at -50 mV increased from 61.74 to 66.57% owing to the enhanced steric exclusion effect, the maximum dwell time was more than doubled from 14.5 to 31.5 ms, and the barrier limited capture rate increased by 8.3 times from 0.46 to 3.85 Hz. As a result, when using 4 M KCl as the electrolyte, over 90% of the PFPeA, PFHxA and PFHpA were accurately identified from a mixed sample, and the calculated limit of detection of PFPeA reached 320 nM, more than 24 times lower than in 2 M KCl. It was thus clear that tuning the electrolyte concentration was a simple but very effective approach to improve the performance of nanopore SMSs for PFCAs determination.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34422083

RESUMO

Background: Type 2 diabetes mellitus (T2DM) is a kind of disorder of glucose and lipid metabolism with the main clinical manifestation of long-term higher blood glucose level than the normal value. Farnesol X receptor (FXR)/ceramide signaling pathway plays an important role in regulating cholesterol metabolism, lipid homeostasis, and the absorption of fat and vitamins in diet. Gegen Qinlian Decoction (GQD) is a classical herbal formula, which has a good clinical therapeutic effect on diabetes-related metabolic syndrome. Objective: To investigate the effect of Gegen Qinlian Decoction (GQD) on hepatic gluconeogenesis in obese T2DM rats based on the FXR/ceramide signaling pathway regulating mitochondrial metabolism and endoplasmic reticulum stress (ERS). Methods: ZDF (fa/fa) rats were fed with high-fat diet to establish the T2DM model; GQD was given to T2DM model rats by gavage; changes of the general state and body weight of rats were recorded; fasting blood glucose was detected; blood insulin, blood ceramide, glycosylated hemoglobin in blood, acetyl CoA in liver mitochondria, and bile salt lyase in intestinal tissue were detected by ELISA. The content of T-ß-MCA in blood was detected by LC-MS; the content of glycogen in liver tissue was detected by PAS staining; the expression of FXR, Sptlc2, and Smpd3 in ileum tissue, P-PERK, ATF6α, GRP78 BIP, and P-IRE1 in the liver, and CS and PC protein in liver mitochondria was detected by immunohistochemistry and western blot assay. The mRNA expression levels of FXR, Sptlc2, and Smpd3 in the ileum, PERK, ATF6α, GRP78 BIP, and IRE1 in the liver, and CS and PC in liver mitochondria were detected by qRT-PCR. Results: GQD can improve the general state of T2DM rats, slow down their weight gain, reduce the levels of fasting blood glucose, fasting insulin, glycosylated hemoglobin, blood ceramide, bile salt hydrolase in intestinal tissue, and acetyl CoA in liver mitochondria of T2DM rats, and increase the contents of liver glycogen and T-ß-MCA in blood of T2DM rats. At the molecular level, GQD can inhibit the expression levels of FXR, Sptlc2, and Smpd3 in the ileum of T2DM rats and the protein and mRNA expression levels of oxidative stress-related factors in the liver. At the same time, GQD can increase the expression of CS and reduce the expression of PC in liver mitochondria of T2DM rats. Conclusion: GQD can inhibit the FXR/ceramide signaling pathway, regulate endoplasmic reticulum stress, enhance the CS activity of liver mitochondria, reduce the acetyl CoA level and PC activity of liver mitochondria, inhibit hepatic gluconeogenesis, protect islet ß-cells, and control blood glucose.

17.
Cancer Cell Int ; 21(1): 414, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362387

RESUMO

BACKGROUND: Ferroptosis, a novel form of regulated cell death, has been implicated in the pathogenesis of cancers. Nevertheless, the potential function and prognostic values of ferroptosis in bladder urothelial carcinoma (BLCA) are complex and remain to be clarified. Therefore, we proposed to systematically examine the roles of ferroptosis-associated genes (FAGs) in BLCA. METHODS: According to The Cancer Genome Atlas (TCGA) database, differently expressed FAGs (DEFAGs) and differently expressed transcription factors (DETFs) were identified in BLCA. Next, the network between DEFAGs and DETFs, GO annotations and KEGG pathway analyses were performed. Then, through univariate, LASSO and multivariate regression analyses, a novel signature based on FAGs was constructed. Moreover, survival analysis, PCA analysis, t-SNE analysis, ROC analysis, independent prognostic analysis, clinicopathological and immune correlation analysis, and experimental validation were utilized to evaluate the signature. RESULTS: Twenty-eight DEFAGs were identified, and four FAGs (CRYAB, TFRC, SQLE and G6PD) were finally utilized to establish the FAGs based signature in the TCGA cohort, which was subsequently validated in the GEO database. Moreover, we found that immune cell infiltration, immunotherapy-related biomarkers and immune-related pathways were significantly different between two risk groups. Besides, nine molecule drugs with the potential to treat bladder cancer were identified by the connectivity map database analysis. Finally, the expression levels of crucial FAGs were verified by the experiment, which were consistent with our bioinformatics analysis, and knockdown of TFRC could inhibit cell proliferation and colony formation in BLCA cell lines in vitro. CONCLUSIONS: Our study identified prognostic ferroptosis-associated genes and established a novel FAGs signature, which could accurately predict prognosis in BLCA patients.

18.
J Biomed Sci ; 28(1): 58, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34364371

RESUMO

Transposable elements (TEs) initially attracted attention because they comprise a major portion of the genomic sequences in plants and animals. TEs may jump around the genome and disrupt both coding genes as well as regulatory sequences to cause disease. Host cells have therefore evolved various epigenetic and functional RNA-mediated mechanisms to mitigate the disruption of genomic integrity by TEs. TE associated sequences therefore acquire the tendencies of attracting various epigenetic modifiers to induce epigenetic alterations that may spread to the neighboring genes. In addition to posting threats for (epi)genome integrity, emerging evidence suggested the physiological importance of endogenous TEs either as cis-acting control elements for controlling gene regulation or as TE-containing functional transcripts that modulate the transcriptome of the host cells. Recent advances in long-reads sequence analysis technologies, bioinformatics and genetic editing tools have enabled the profiling, precise annotation and functional characterization of TEs despite their challenging repetitive nature. The importance of specific TEs in preimplantation embryonic development, germ cell differentiation and meiosis, cell fate determination and in driving species specific differences in mammals will be discussed.

19.
Front Aging Neurosci ; 13: 689276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408642

RESUMO

Partly because of extensions in lifespan, the incidence of neurodegenerative diseases is increasing, while there is no effective approach to slow or prevent neuronal degeneration. As we all know, neurons cannot self-regenerate and may not be replaced once being damaged or degenerated in human brain. Astrocytes are widely distributed in the central nervous system (CNS) and proliferate once CNS injury or neurodegeneration occur. Actually, direct reprogramming astrocytes into functional neurons has been attracting more and more attention in recent years. Human astrocytes can be successfully converted into neurons in vitro. Notably, in vivo direct reprogramming of astrocytes into functional neurons were achieved in the adult mouse and non-human primate brains. In this review, we briefly summarized in vivo direct reprogramming of astrocytes into functional neurons as regenerative strategies for CNS diseases, mainly focusing on neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). We highlight and outline the advantages and challenges of direct neuronal reprogramming from astrocytes in vivo for future neuroregenerative medicine.

20.
Biomed Pharmacother ; 141: 111853, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34237593

RESUMO

The degranulation of cardiac mast cells is associated with occurrence and development of myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has a cardioprotective effect from I/R injury. The purpose of this study was to investigate whether dexmedetomidine preconditioning induced cardioprotection is related to suppression of degranulation of cardiac mast cell. Both in vivo and in vitro experimental results revealed that hemodynamic disorder, arrhythmia, infarct size, histopathological score, and mast cell degranulation were dramatically increased in I/R injury groups compared with non-I/R groups, and mastocyte secretagogue compound 48/80 aggravated these damages, but it can be improved by dexmedetomidine preconditioning. Similarly, compound 48/80 increased levels of cardiac troponin I (cTnI) and tryptase, cardiomyocytes apoptosis, and expression of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), and nuclear factor-kappa B p65 (NF-κB p65) in cardiac tissues induced by I/R injury, but it can be partially decreased by dexmedetomidine pretreatment. Compound 48/80 inhibited proliferation of H9C2(2-1) and RBL-2H3, exacerbated apoptosis of H9C2(2-1), and elevated levels of cTnI and tryptase, while both of which were abolished by dexmedetomidine pretreatment. Our data suggest that dexmedetomidine preconditioning alleviates the degranulation of mast cells and the apoptosis of cardiomyocytes caused by I/R injury, and inhibits the activation of inflammatory related factors HMGB1, TLR4, and NF-κB p65.

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