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1.
Zool Res ; 43(1): 52-63, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34821086

RESUMO

The ability to sense temperature changes is crucial for mammalian survival. Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels (Thermo-TRPs). Some mammals hibernate to survive cold winter conditions, during which time their body temperature fluctuates dramatically. However, the underlying mechanisms by which these mammals regulate thermal responses remain unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) and the Western blotting, we found that Myotis ricketti bats had high levels of heat-activated TRPs (e.g., TRPV1 and TRPV4) during torpor in winter and cold-activated TRPs (e.g., TRPM8 and TRPC5) during active states in summer. We also found that laboratory mice had high mRNA levels of cold-activated TRPs (e.g., Trpm8 and Trpc5) under relatively hot conditions (i.e., 40 °C). These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions. Binding site analysis showed that some homeobox (HOX) transcription factors (TFs) regulate the expression of hot- and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc (POU) family regulate warm-sensitive and cold-activated TRP genes. The dual-luciferase reporter assay results demonstrated that TFs HOXA9, POU3F1, and POU5F1 regulate TRPC5 expression, suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels. This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.


Assuntos
Quirópteros , Temperatura Alta , Estações do Ano , Canais de Cátion TRPC , Animais , Quirópteros/genética , Feminino , Hibernação/genética , Masculino , Camundongos , Canais de Cátion TRPC/genética , Canais de Cátion TRPV/genética
2.
World J Clin Cases ; 9(32): 9783-9791, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34877317

RESUMO

BACKGROUND: Severe bony Bankart lesions are a difficult challenge in clinical treatment and research. The current treatment methods consist mostly of Latarjet-Bristow surgery and its modified procedures. While good results have been achieved, there are also complications such as coracoid fracture, bone graft displacement, and vascular and nerve injury. AIM: To analyze the techniques and biomechanical properties of transversely fixing a bone block from the scapular spine using bone allograft pins with suture threads to repair bony Bankart lesions. METHODS: Fresh human shoulder joint specimens and a cadaver specimen model for scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions were used. When the humeral rotation angles were 0°, 30°, 60° and 90°, and the axial loads were 30 N, 40 N, and 50 N, the humerus displacement was studied by biomechanical experiments. RESULTS: When the angle of external rotation of the humerus was 0°, 30°, 60°, and 90°, with axial loads of 30 N, 40 N, and 50 N, the data of the normal control group, allograft pin repair group, and titanium alloy hollow screw repair group were compared with each other by the q-test, which showed that there were no statistically differences among the three groups (P > 0.05). CONCLUSION: The joints repaired with bone block from the scapular spine transversely fixed with allograft bony pins to repair bony Bankart lesions show good mechanical stability. The bone block has similar properties to normal glenohumeral joints in terms of biomechanical stability.

3.
Inorg Chem ; 60(23): 18473-18482, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34797628

RESUMO

Acetylene (C2H2) purification is of great importance for many chemical synthesis and processes. Metal-organic frameworks (MOFs) are widely used for gas adsorption and separation due to their variable structure and porosity. However, the exploitation of ideal MOF adsorbents for C2H2 keeps a challenging task. Herein, a combination of open metal sites (OMSs) and Lewis basic sites (LBSs) in robust MOFs is demonstrated to effectively promote the C2H2 purification performance. Accordingly, SNNU-37(Fe/Sc), two isostructural MOFs constituted by [Fe3O(COO)6] or [Sc3O(COO)6] trinuclear clusters and amide-functionalized tricarboxylate linkers, were designed with extra-stable 3,6-connected new architectures. Derived from the coexistence of high-density OMSs and LBSs, the C2H2 adsorption amounts of SNNU-37(Fe/Sc) are much higher than those values for C2H4 and CO2. Theoretical IAST selectivity values of SNNU-37(Fe) are 2.4 for C2H2/C2H4 (50/50, v/v) and 9.9 for C2H2/CO2 (50/50, v/v) at 298 K and 1 bar, indicating an excellent C2H2 separation ability. Experimental breakthrough curves also revealed that SNNU-37(Fe) could effectively separate C2H2/C2H4 and C2H2/CO2 under ambient conditions. GCMC simulations further indicate that open Fe or Sc sites and amide groups mainly contribute to stronger adsorption sites for C2H2 molecules.

4.
Sensors (Basel) ; 21(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34640891

RESUMO

To construct circular barrier coverage (CBC) with multistatic radars, a deployment optimization method based on equipartition strategy is proposed in this paper. In the method, the whole circular area is divided into several sub-circles with equal width, and each sub-circle is blanketed by a sub-CBC that is built based on the multistatic radar deployment patterns. To determine the optimal deployment patterns for each sub-CBC, the optimization conditions are firstly studied. Then, to optimize the deployment of the whole circular area, a model based on minimum deployment cost is proposed, and the proposed model is divided into two sub-models to solve the optimization issue. In the inner model, it is assumed that the width of a sub-circle is given. Based on the optimization conditions of the deployment pattern, integer linear programming (ILP) and exhaustive method (EM) are jointly adopted to determine the types and numbers of deployment patterns. Moreover, a modified formula is introduced to calculate the maximum valid number of receivers in a pattern, thus narrowing the search scope of the EM. In the outer model, the width of a sub-circle is assumed to be a variable, and the EM is adopted to determine the minimum total deployment cost and the optimal deployment patterns on each sub-circle. Moreover, the improved formula is exploited to determine the range of width for a sub-circle barrier and reduce the search scope of the EM. Finally, simulations are conducted in different conditions to verify the effectiveness of the proposed method. The simulation results indicate that the proposed method can spend less deployment cost and deploy fewer transmitters than the state-of-the-artwork.

5.
Clin Lung Cancer ; 22(1): e98-e111, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33067127

RESUMO

BACKGROUND: There occurs huge heterogeneity in clinical outcomes for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The purpose of this study was to indicate genetic biomarkers predicting primary resistance of EGFR-TKIs in these patients. PATIENTS AND METHODS: Using a next-generation sequencing panel with 168 cancer-related genes, matched tumor biopsy and plasma samples before treatments from patients with NSCLC were analyzed. Patients taking EGFR-TKIs were followed-up with imaging examination. Correlation of co-alterative genes with progression-free survival (PFS) was analyzed. RESULTS: Of the 48 patients treated with EGFR-TKIs, 46 (95.83%) had at least 1 genetic co-variant beyond EGFR mutation. Multivariate analysis indicated that RB1, PIK3CA, and ERBB2 co-alterations, rather than number of co-alterative genes, were independently associated with poorer PFS. Grouping patients by specific gene status showed best likelihood ratio χ2, Akaike information criterion, and Harrell concordance index. The median PFS for patients in group A (less genetic co-variations and wild specific genes), group B (more genetic co-variations and wild specific genes), group C (less genetic co-variations and altered specific genes), and group D (more genetic co-variations and altered specific genes) were 10.4, 9.13 (vs. group A; P = .3112), 6.33 (vs. group B; P = .0465), and 3.90 (vs. group C; P = .0309) months, respectively. CONCLUSIONS: This study revealed a high concomitant genetic alteration rate in patients with EGFR-mutated NSCLC. Specific gene variants were more important than number of altered genes in predicting poor PFS, and may help select patients needing new treatment strategies.

6.
Biochim Biophys Acta Mol Cell Res ; 1868(1): 118855, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926941

RESUMO

Dysfunctions of vascular smooth muscle cells (VSMCs) play crucial roles in vascular remodeling in hypertension, which correlates with pathologically elevated cyclic stretch due to increased arterial pressure. Recent researches reported that autophagy, a life-sustaining process, was increased in hypertension. However, the mechanobiological mechanism of VSMC autophagy and its potential roles in vascular remodeling are still unclear. Using renal hypertensive rats in vivo and FX5000 stretch application Unit in vitro, the autophagy of VSMCs was detected. The results showed that LC3II remarkably enhanced in hypertensive rats and 15% cyclic stretch (mimic the pathologically increased mechanical stretch in hypertension), and the activity of mammalian target of rapamycin (mTOR) was suppressed in 15% cyclic stretch. Administration of autophagy inhibitors, bafilomycin A1 and chloroquine, repressed VSMC proliferation efficiently, but did not affect the degradation of two important nuclear envelope (NE) proteins, lamin A/C and emerin. Using RNA interference to decline the expression of lamin A/C and emerin, respectively, we discovered that autophagy was upregulated under both static and 5% cyclic stretch conditions, accompanying with the decreased mTOR activity. During 15% cyclic stretch application, mTOR inhibition was responsible for autophagy elevation. Chloroquine administration in vivo inhibited the expression of PCNA (marker of proliferation) of abdominal aorta in hypertensive rats. Altogether, these results demonstrated that pathological cyclic stretch suppresses the expression of lamin A/C and emerin which subsequently represses mTOR pathway so as to induce autophagy activation. Blocking autophagic flux may be a practicable way to relieve the pathological vascular remodeling in hypertensive.


Assuntos
Autofagia/genética , Hipertensão/genética , Lamina Tipo A/genética , Proteínas de Membrana/genética , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Proteínas Nucleares/genética , Animais , Proliferação de Células/efeitos dos fármacos , Cloroquina/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Masculino , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Membrana Nuclear/genética , Ratos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Remodelação Vascular/efeitos dos fármacos
7.
Inorg Chem ; 59(22): 16725-16736, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33152248

RESUMO

Both methane (CH4) and acetylene (C2H2) are important energy source and raw chemicals in many industrial processes. The development of an energy-efficient and environmentally friendly separation and purification strategy for CH4 and C2H2 is necessary. Ultramicroporous metal-organic framework (MOF) materials have shown great success in the separation and purification of small-molecule gases. Herein, the synergy effect of tritopic polytetrazolate and ditopic terephthalate ligands successfully generates a series of isoreticular ultramicroporous cadmium tetrazolate-carboxylate MOF materials (SNNU-13-16) with excellent CH4 and C2H2 purification performance. Except for the uncoordinated tetrazolate N atoms serving as Lewis base sites, the pore size and pore surface of MOFs are systematically engineered by regulating dicarboxylic acid ligands varying from OH-BDC (SNNU-13) to Br-BDC (SNNU-14) to NH2-BDC (SNNU-15) to 1,4-NDC (SNNU-16). Benefiting from the ultramicroporous character (3.8-5.9 Å), rich Lewis base N sites, and tunable pore environments, all of these ultramicroporous MOFs exhibit a prominent separation capacity for carbon dioxide (CO2) or C2 hydrocarbons from CH4 and C2H2. Remarkably, SNNU-16 built by 1,4-NDC shows the highest ideal adsorbed solution theory CO2/CH4, ethylene (C2H4)/CH4, and C2H2/CH4 separation selectivity values, which are higher than those of most famous MOFs with or without open metal sites. Dynamic breakthrough experiments show that SNNU-16 can also efficiently separate the C2H2/CO2 mixtures with a gas flow rate of 4 mL min-1 under 1 bar and 298 K. The breakthrough time (18 min g-1) surpasses most best-gas-separation MOFs and nearly all other metal azolate-carboxylate MOF materials under the same conditions. The above prominently CH4 and C2H2 purification abilities of SNNU-13-16 materials were further confirmed by the Grand Canonical Monte Carlo (GCMC) simulations.

8.
Sheng Li Xue Bao ; 72(4): 506-512, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32820313

RESUMO

Alzheimer's disease (AD) is currently the most prevalent neurodegenerative disease in the aging population. It is characterized by massive deposition of extracellular ß-amyloid peptide and formation of intracellular neurofibrillary tangles. Cancer is also an age-related disease. Some epidemiological studies have shown an inverse relationship between AD and the onset of various types of cancers, that is, the risk of cancer in patients with AD is reduced, and vice versa. Epigenetic mechanisms play important roles in the development of AD and cancer. In this article, we will review the recent research advances on the epigenetic mechanisms of AD and cancer onset, and provide new ideas for rethinking the relevance of AD and cancer with a "holistic concept".


Assuntos
Doença de Alzheimer , Neoplasias , Doenças Neurodegenerativas , Idoso , Epigênese Genética , Humanos , Emaranhados Neurofibrilares
9.
ACS Appl Mater Interfaces ; 12(22): 24786-24795, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32372639

RESUMO

As an important organic intermediate, benzonitrile (BN) is widely involved in organic synthetic chemistry and pharmaceutical and dyestuff industries. However, the exploration of a more efficient and controllable synthesis technique and the corresponding greener catalysts for the synthesis of BN still poses a great challenge. Herein, with multimetallic two-dimensional conductive metal-organic frameworks (2D cMOF) as anodic electrocatalysts, we develop a green, convenient, and highly efficient electrochemical synthesis strategy for BN. Thanks to the intrinsic 2D electrically conductive structure and the optimized the multimetallic coupling catalytic effect, the resulting multimetallic 2D cMOFs exhibit excellent benzylamine (BA) electrooxidation performance. Especially, the trimetallic 2D cMOF (NiCoFe-CAT) requires an ultralow potential of 1.29 V vs reversible hydrogen electrode (RHE) to achieve a 10 mA·cm-2 current density, which indicates the fastest reaction and the most favorable thermodynamic condition. A very high yield (0.058 mmol·mg-1·h-1) and faradic efficiency (∼87%) of benzonitrile are both achieved during the BA electrooxidation reaction at 1.45 V. The reaction mechanism investigations indicated that the various redox mediators of MII/MIII (Ni, Co, Fe) may be regarded as multimetal active species to promote BA conversion. Also, the excellent cycling durability of multimetallic 2D cMOFs further promotes their potential practical applications. These electrocatalytic performances are considered excellent and nearly surpass all other reported Ni-based inorganics or MOF-based electrocatalysts for the electrocatalytic oxidation of benzylamine.

10.
Natl Sci Rev ; 7(6): 952-963, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34692117

RESUMO

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the EPAS1 gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the gene C10orf67, which underwent positive selection in three of the domestic mammals. Our data provide an insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway.

11.
Acta Physiol (Oxf) ; 228(3): e13374, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31495066

RESUMO

AIM: Apoptosis of vascular smooth muscle cells (VSMCs) influenced by abnormal cyclic stretch is crucial for vascular remodelling during hypertension. Lamin A/C, a nuclear envelope protein, is mechano-responsive, but the role of lamin A/C in VSMC apoptosis is still unclear. METHODS: FX-5000T Strain Unit provided cyclic stretch (CS) in vitro. AnnexinV/PI and cleaved Caspase 3 ELISA detected apoptosis. qPCR was used to investigate the expression of miR-124-3p and a luciferase reporter assay was used to evaluate the ability of miR-124-3p binding to the Lmna 3'UTR. Protein changes of lamin A/C and relevant molecules were detected using western blot. Ingenuity Pathway Analysis and Protein/DNA array detected the potential transcription factors. Renal hypertensive rats verified these changes. RESULTS: High cyclic stretch (15%-CS) induced VSMC apoptosis and repressed lamin A/C expressions compared with normal (5%-CS) control. Downregulation of lamin A/C enhanced VSMC apoptosis. In addition, 15%-CS had no significant effect on mRNA expression of Lmna, and lamin A/C degradation was not induced by autophagy. 15%-CS elevated miR-124-3p bound to the 3'UTR of Lmna and negatively regulated protein expression of lamin A/C. Similar changes occurred in renal hypertensive rats compared with sham controls. Lamin A/C repression affected activity of TP53, CREB1, MYC, STAT1/5/6 and JUN, which may in turn affect apoptosis. CONCLUSION: Our data suggested that the decreased expression of lamin A/C upon abnormal cyclic stretch and hypertension may induce VSMC apoptosis. These mechano-responsive factors play important roles in VSMC apoptosis and might be novel therapeutic targets for vascular remodelling in hypertension.


Assuntos
Hipertensão/patologia , Lamina Tipo A/antagonistas & inibidores , MicroRNAs/genética , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Animais , Apoptose/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Hipertensão/genética , Hipertensão/metabolismo , Masculino , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Estresse Mecânico
12.
ACS Appl Mater Interfaces ; 12(4): 4432-4442, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31838854

RESUMO

It is well-known that the formation of ferroalloy with the addition of the second or third metal during the steel-making process usually can improve the performance of the iron. Inspired by ferroalloy materials, it is speculated that the pore environment, framework charge, and catalytic properties of metal-organic frameworks (MOFs) could be optimized dramatically via the introduction of ferroalloy-like inorganic building blocks. However, different to ferroalloy, the accurate integration of different metals into one MOF platform is still challenging. Herein, taking advantages of the good compatibility for metals in trigonal prismatic trinuclear cluster, a series of Fe-based alloy-like [M3O(O2C)6] motifs (M3 = Fe3, Fe1.5Ni1.5, Fe1.5Co1.5, Fe1.5Ti1.5, FeCoNi, and FeTiCo) are successfully generated, which further lead to a robust Fe-MOF material family (SNNU-5s). These multicomponent MOFs not only provide a good chance to explore the impact of pore environment on gas adsorption/separation but also offer an opportunity to the efficient electrocatalytic reaction directly. Accordingly, compared with the SNNU-5-Fe parent structure, the pore characters of heterometallic SNNU-5 MOFs are clearly regulated by the type of alloy-like building blocks. SNNU-5-FeTi displays more superior gas separation performance for CO2/CH4, C2H2/CH4, C2H4/CH4, and C2H2/CO2 gas mixtures. What is more, benefited from the multimetallic active sites and their catalytic synergy, FeCoNi-ternary alloy-like cluster-based SNNU-5 MOF material exhibits an exceptional oxygen evolution reaction activity in aqueous solution at pH = 13, which delivers a low overpotential (ηj=10 = 317 mV), a fast reaction kinetics (Tafel slope = 37 mV dec-1), and excellent catalytic stability. This facile multialloy-like building block strategy holds promise to accurately design and improve the performance of MOFs, as well as open an avenue to understand the related mechanisms.

13.
Inorg Chem ; 58(16): 11220-11230, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31368311

RESUMO

The detection of nitro compounds and removal of organic dyes remain urgent issues because they are poisonous to humans. Taking advantage of metal-organic framework (MOF) materials, we demonstrate herein an indium-organic framework (InOF) exhibiting sensitive fluorescence sensing of nitro compounds, prominent dye capture, and excellent photodegradation of dyes. By using 4,4',4″-s-triazine-1,3,5-triyltri-p-aminobenzoate (TATAB), an amino-functionalized BTB-like linker, the 3D SNNU-110 structure ({[In3OCl(H2O)2(TATAB)2]}n) is formed. SNNU-110 shows a 3,6-connected 3,6T22 topology with TATAB and [In3O(CO2)6] tricapped trigonal-prismatic clusters as 3- and 6-connected nodes. Thanks to the fluorescence properties and amine recognition sites of TATAB, SNNU-110 exhibits excellent performance of fluorescence quenching for six electron-deficient nitroaromatics. The intercrossing 1D channels in SNNU-110 formed from the a- and b-axis directions with dimensions of about 18 Å × 11 Å can capture diverse cationic, anionic, or neutral dyes effectively. What is more, the existence of an inorganic [In3O] cluster enable SNNU-110 to be a good photocatalyst. Upon irradiation with a 300 W xenon lamp, SNNU-110 shows outstanding photocatalytic activity toward rhodamine B (RhB) and methylene blue (MB), and there was almost no degradation. The catalytic activity can retain about 94.6% (RhB) and 93.1% (MB), respectively. Overall, SNNU-110 fully demonstrates the power of multicomponent MOFs, which provide a feasible route for the design of functional materials toward to pollutant identification and removal applications.

14.
Angew Chem Int Ed Engl ; 58(38): 13590-13595, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31407503

RESUMO

A strategy called ultramicroporous building unit (UBU) is introduced. It allows the creation of hierarchical bi-porous features that work in tandem to enhance gas uptake capacity and separation. Smaller pores from UBUs promote selectivity, while larger inter-UBU packing pores increase uptake capacity. The effectiveness of this UBU strategy is shown with a cobalt MOF (denoted SNNU-45) in which octahedral cages with 4.5 Špore size serve as UBUs. The C2 H2 uptake capacity at 1 atm reaches 193.0 cm3 g-1 (8.6 mmol g-1 ) at 273 K and 134.0 cm3 g-1 (6.0 mmol g-1 ) at 298 K. Such high uptake capacity is accompanied by a high C2 H2 /CO2 selectivity of up to 8.5 at 298 K. Dynamic breakthrough studies at room temperature and 1 atm show a C2 H2 /CO2 breakthrough time up to 79 min g-1 , among top-performing MOFs. Grand canonical Monte Carlo simulations agree that ultrahigh C2 H2 /CO2 selectivity is mainly from UBU ultramicropores, while packing pores promote C2 H2 uptake capacity.

15.
J Clin Neurosci ; 65: 125-133, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31036506

RESUMO

The present study focused on the novel roles and the underlying mechanisms of miR-135b in pyroptosis of MPP+-induced Parkinson's disease (PD). We established an in vitro PD model induced by MPP+. Our results demonstrated miR-135b was lower while FoxO1 was inversely higher in MPP+-treated SH-SY5Y and PC-12 cells. Luciferase reporter assay showed FoxO1 was a downstream target of miR-135b. MiR-135b mimics suppressed MPP+-induced pyroptosis and the upregulation of TXNIP, NLRP3, Caspase-1, ASC, GSDMDNterm and IL-1ß. Moreover, FoxO1 overexpression had no effect on miR-135b but reversed its own downregulation caused by miR-135b mimics. Meanwhile, overexpression of FoxO1 abolished the inhibitory effects of miR-135b on pyroptosis and reversed the downregulation of pyroptotic genes and LDH release. In summary, miR-135b played a protective role in Parkinson's disease via inhibiting pyroptosis by targeting FoxO1. MiR-135b might serve as a potential therapeutic target in the treatment of Parkinson's disease.


Assuntos
Proteína Forkhead Box O1/metabolismo , Inflamassomos/metabolismo , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doença de Parkinson/genética , Piroptose/genética , Proteínas de Transporte/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Neoplasias/genética , Proteínas de Ligação a Fosfato , Regulação para Cima
16.
Exp Cell Res ; 376(1): 77-85, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690026

RESUMO

Cyclic stretch regulates proliferation of vascular smooth muscle cells (VSMCs) during hypertension-induced vascular remodeling, but the underlying mechanisms remain to be studied. Connective tissue growth factor (CTGF) has been reported associated with several cellular function such as proliferation,migration and adhesion. Herein, the role of CTGF in VSMCs was investigated in response to mechanical cyclic stretch. Here we show that CTGF is up-regulated both in vivo and in vitro during hypertension. Overexpression of CTGF markedly promoted VSMC proliferation, whereas CTGF knockdown attenuated cyclic stretch-induced proliferation. Furthermore, 3'UTR reporter assays revealed that microRNA-19b-3p (miR-19b-3p) directly regulates CTGF expression. Under pathological condition (e.g. 15% cyclic stretch), miR-19b-3p expression was significantly down-regulated; conversely miR-19b-3p overexpression blocked VSMC proliferation. Taken together, these findings indicate that pathological cyclic stretch induces vascular remodeling by promoting VSMC proliferation via miR-19b-3p/CTGF pathway, and point to CTGF as a potential therapeutic target for hypertension.


Assuntos
Proliferação de Células/genética , Fator de Crescimento do Tecido Conjuntivo/genética , Hipertensão/genética , MicroRNAs/genética , Músculo Liso Vascular/crescimento & desenvolvimento , Regiões 3' não Traduzidas/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Músculo Liso Vascular/metabolismo , Transdução de Sinais/genética
17.
Mol Biol Evol ; 36(3): 487-499, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30481341

RESUMO

The origin and population history of the endangered golden snub-nosed monkey (Rhinopithecus roxellana) remain largely unavailable and/or controversial. We here integrate analyses of multiple genomic markers, including mitochondrial (mt) genomes, Y-chromosomes, and autosomes of 54 golden monkey individuals from all three geographic populations (SG, QL, and SNJ). Our results reveal contrasting population structures. Mt analyses suggest a division of golden monkeys into five lineages: one in SNJ, two in SG, and two in QL. One of the SG lineages (a mixed SG/QL lineage) is basal to all other lineages. In contrast, autosomal analyses place SNJ as the most basal lineage and identify one QL and three SG lineages. Notably, Y-chromosome analyses bear features similar to mt analyses in placing the SG/QL-mixed lineage as the first diverging lineage and dividing SG into two lineages, while resembling autosomal analyses in identifying one QL lineage. We further find bidirectional gene flow among all three populations at autosomal loci, while asymmetric gene flow is suggested at mt genomes and Y-chromosomes. We propose that different population structures and gene flow scenarios are the result of sex-linked differences in the dispersal pattern of R. roxellana. Moreover, our demographic simulation analyses support an origin hypothesis suggesting that the ancestral R. roxellana population was once widespread and then divided into SNJ and non-SNJ (SG and QL) populations. This differs from previous mt-based "mono-origin (SG is the source population)" and "multiorigin (SG is a fusion of QL and SNJ)" hypotheses. We provide a detailed and refined scenario for the origin and population history of this endangered primate species, which has a broader significance for Chinese biogeography. In addition, this study highlights the importance to investigate multiple genomic markers with different modes of inheritance to trace the complete evolutionary history of a species, especially for those exhibiting differential or mixed patterns of sex dispersal.


Assuntos
Distribuição Animal , Cercopithecidae/genética , Espécies em Perigo de Extinção , Fluxo Gênico , Animais , China , Genoma Mitocondrial , Desequilíbrio de Ligação , Masculino , Filogenia , Filogeografia , Polimorfismo de Nucleotídeo Único , Cromossomo Y
18.
PLoS One ; 13(11): e0206757, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30412616

RESUMO

In this study, we examined the role of mRNAs and miRNAs in variations in intramuscular fat content in the longissimus dorsi muscle in Xinjiang brown cattle. Two groups of Xinjiang brown cattle with extremely different intramuscular fat content in the longissimus dorsi were selected for combined of miRNA and mRNA analysis using an RNA-Seq. In total, 296 mRNAs and 362 miRNAs were significantly differentially expressed, including 155 newly predicted miRNAs, 275 significantly upregulated genes, 252 significantly upregulated miRNAs, 21 significantly downregulated genes and 110 significantly downregulated miRNAs. The combined miRNA and mRNA analysis identified 96 differentially expressed miRNAs and 27 differentially expressed mRNAs. In all, 47 upregulated miRNAs had a regulatory effect on 14 differentially downregulated target genes, and 49 downregulated miRNAs had a regulatory effect on 13 upregulated target genes. To verify the sequencing results, 10 differentially expressed genes (DEGs) and 10 differentially expressed miRNAs were selected for qRT-PCR. The qRT-PCR results confirmed the sequencing results. The results of this study shed light on the molecular regulation of bovine adipose tissue, which might help with the development of new strategies for improving meat quality and animal productivity in beef cattle to provide healthier meat products for consumers.


Assuntos
Tecido Adiposo/metabolismo , Bovinos/metabolismo , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , RNA Mensageiro/metabolismo , Tecido Adiposo/anatomia & histologia , Animais , Bovinos/anatomia & histologia , Qualidade dos Alimentos , Regulação da Expressão Gênica , Carne , Músculo Esquelético/anatomia & histologia
19.
Arch Med Sci ; 14(4): 752-759, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30002691

RESUMO

Introduction: The long non-coding RNAs (lncRNAs) urothelial cancer associated 1 (UCA1) and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) are known to impact cancer cell regulation. The aim of the present study was to determine the relationship between the expression of these lncRNAs in esophageal squamous cell carcinoma (ESCC) tissues and disease prognosis. Material and methods: The expression of UCA1 and MALAT1 lncRNAs was assessed in ESCC and adjacent carcinoma tissues (5 cm away from the tumor) and evaluated in relation to overall survival (OS) and disease-free survival (DFS) of patients. This prospective study included 100 ESCC patients who were admitted to the First Hospital of Yulin City between January 2007 and January 2014. Results: The expression levels of UCA1 and MALAT1 lncRNAs in ESCC tissues were significantly higher than those in adjacent carcinoma tissues, and there were statistically significant differences in TNM staging between the patients with high lncRNA expression and low lncRNA expression. The OS and DFS of patients with high UCA1 and MALAT1 lncRNA expression levels were significantly shorter than those with low expression levels. Furthermore, the OS and DFS of ESCC patients appeared to be correlated with TNM staging. Conclusions: These results imply that the up-regulation of UCA1 and MALAT1 lncRNAs in ESCC tissues can impact the degree of tumor progression and is predictive of postoperative survival. Therefore, the expression levels of these lncRNAs can be used as measurement indexes to determine the prognosis of ESCC patients.

20.
Mol Biol Evol ; 35(1): 149-158, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29087519

RESUMO

The geographic origin and migration of the brown rat (Rattus norvegicus) remain subjects of considerable debate. In this study, we sequenced whole genomes of 110 wild brown rats with a diverse world-wide representation. We reveal that brown rats migrated out of southern East Asia, rather than northern Asia as formerly suggested, into the Middle East and then to Europe and Africa, thousands of years ago. Comparison of genomes from different geographical populations reveals that many genes involved in the immune system experienced positive selection in the wild brown rat.


Assuntos
Filogeografia/métodos , Ratos/genética , África , Animais , Ásia Sudeste/epidemiologia , Evolução Biológica , Europa (Continente) , Evolução Molecular , Variação Genética/genética , Genética Populacional , Genoma/genética , Oriente Médio , Filogenia , Sequenciamento Completo do Genoma/métodos
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