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1.
Life Sci ; 348: 122701, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38724005

RESUMO

Hyperinflammatory responses are pivotal in the cardiomyocyte senescence pathophysiology, with IL33 serving as a crucial pro-inflammatory mediator. Our previous findings highlighted RND3's suppressive effect on IL33 expression. This study aims to explore the role of RND3 in IL33/ST2 signaling activation and in cardiomyocyte senescence. Intramyocardial injection of exogenous IL33 reduces the ejection fraction and fractional shortening of rats, inducing the appearance of senescence-associated secretory phenotype (SASP) in myocardial tissues. Recombinant IL33 treatment of AC16 cardiomyocytes significantly upregulated expression of SASP factors like IL1α, IL6, and MCP1, and increased the p-p65/p65 ratio and proportions of SA-ß-gal and γH2AX-positive cells. NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) and ST2 antibody astegolimab treatments mitigated above effects. RND3 gene knockout H9C2 cardiomyocytes using CRISPR/Cas9 technology upregulated IL33, ST2L, IL1α, IL6, and MCP1 levels, decreased sST2 levels, and increased SA-ß-gal and γH2AX-positive cells. A highly possibility of binding between RND3 and IL33 proteins was showed by molecular docking and co-immunoprecipitation, and loss of RND3 attenuated ubiquitination mediated degradation of IL33; what's more, a panel of ubiquitination regulatory genes closely related to RND3 were screened using qPCR array. In contrast, RND3 overexpression in rats by injection of AAV9-CMV-RND3 particles inhibited IL33, ST2L, IL1α, IL6, and MCP1 expression in cardiac tissues, decreased serum IL33 levels, and increased sST2 levels. These results suggest that RND3 expression in cardiomyocytes modulates cell senescence by inhibiting the IL33/ST2/NF-κB signaling pathway, underscoring its potential as a therapeutic target in cardiovascular senescence.


Assuntos
Senescência Celular , Interleucina-33 , Miócitos Cardíacos , Transdução de Sinais , Animais , Masculino , Ratos , Linhagem Celular , Senescência Celular/efeitos dos fármacos , Interleucina-33/metabolismo , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Receptores de Interleucina-1 , Proteínas rho de Ligação ao GTP/metabolismo , Proteínas rho de Ligação ao GTP/genética
2.
Nurse Educ Today ; 138: 106194, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38640841

RESUMO

BACKGROUND: Graduate nursing education plays an important role in the development of an innovative nation. Such education benefits the health of the community by cultivating competent and highly skilled nurses who can provide safe and quality nursing care. The number of students pursuing nursing degrees in China is insufficient, to meet the social demand for advanced practice nurses. The part-time Master of Nursing Specialist program for students offers flexible learning options for working nurses. However, the relatively low level of learning engagement exhibited by this group has raised concerns among policy-makers and nursing educators. An in-depth study of the factors affecting the learning engagement of part-time Master of Nursing Specialist postgraduates, especially with regard to their combined effect, is expected to provide a basis for improving the level of learning engagement among such students. METHODS: This study used ability-motivation-opportunity-theory and fuzzy-set qualitative comparative analysis to analyze the relationships between five conditions (i.e., supportive campus environment, supportive work environment, student-faculty interaction, research motivation and time management ability) and learning engagement by reference to data collected from a sample of 225 part-time Master of Nursing Specialist students who were enrolled in China. RESULTS: The fuzzy-set qualitative comparative analysis results indicated that individual examples of these antecedent conditions were insufficient to influence learning engagement. In contrast, three combinations of the five conditions led to high levels of learning engagement, and substitutability and complementarity were observed among the various elements in the configuration. CONCLUSIONS: Research motivation, student-faculty interaction, a supportive work environment and time management are factors that can influence part-time postgraduates' learning engagement. Supervisors can enhance their research skills and expertise, hospitals can establish supportive environments for students, and students can strengthen their research motivation and time management abilities.


Assuntos
Educação de Pós-Graduação em Enfermagem , Aprendizagem , Pesquisa Qualitativa , Estudantes de Enfermagem , Humanos , China , Estudantes de Enfermagem/psicologia , Estudantes de Enfermagem/estatística & dados numéricos , Educação de Pós-Graduação em Enfermagem/métodos , Feminino , Masculino , Motivação , Adulto , Local de Trabalho/psicologia , Gerenciamento do Tempo , População do Leste Asiático
3.
Chemosphere ; 355: 141835, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552799

RESUMO

This study provides insights regarding the selective metal leaching of brass in various tap water conditions, which benefits water utilities to predict the potential of metal released from brass water meters. The long-term time-dependent selective metal dissolution of brass with various ß phase fractions have not previously been investigated. In this study, a 201-d immersion experiment was carried out in low and high conductivity tap water (LCTW and HCTW, respectively). Three commercialized brass samples in different ß phase fractions (ß = 51%, ß = 43%, ß = 39%), named brass 51, brass 43, and brass 39, respectively, were used. The results showed that brass 51 had the most negative corrosion potential (-0.17 V) and the lowest polarization resistance (8.5 kΩ) compared to brass 43 and brass 39 (-0.04 V and 10.1-14.7 kΩ, respectively) in LCTW. This trend was verified by the 201-d immersion experiment in which brass 51 exhibited the highest zinc leaching rate (21-30 µg L-1 cm-2 d-1), followed by brass 43 and brass 39 (16-23 µg L-1 cm-2 d-1) in both waters. The leaching amounts of lead and copper were extremely low compared to zinc. In LCTW, the uniform corrosion (UC) mechanism dominated from day 1 to day 120. Afterwards, UC was replaced by the galvanic corrosion (GC) mechanism, with the selective leaching coefficient of Zn over Cu (SZn/Cu) increasing from 10 to 25 to 40-80. In HCTW, however, the SZn/Cu reached 300-1000, and the transition of UC to GC occurred earlier on day 30 due to the rapid formation of the ZnO layer on the brass surface that hindered the ion attack.


Assuntos
Cobre , Água , Chumbo , Zinco
4.
Environ Sci Pollut Res Int ; 30(55): 117846-117861, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37875758

RESUMO

Sulfur (S)-doped α-Fe2O3 has been regarded as an excellent catalyst for eliminating organic pollutants in the photo-Fenton-like reaction. Yet, the synthetic complexity and extremely low activity in the dark Fenton-like reaction still need to be solved. In this study, magnetic α-Fe2O3 with sulfide was successfully fabricated via hydrothermal and calcination processes, for the first time, where thiourea acted as both S source and reducing agent, and then, it was applied for activating peroxydisulfate (PDS) to degrade organic contaminants. Important influencing factors were systemically investigated, and the results showed that this catalyst activating PDS was highly effective in the removal of organic pollutants in dark- and photo-Fenton-like reactions. In addition, the catalyst possessed good stability and recyclable ability. The structure of catalyst was analyzed by several characterizations, such as XRD and XPS. The results revealed that sulfide had an important effect on the structure and performance of α-Fe2O3. The detected mechanism indicated that the main reactive oxygen species were altered after switching from darkness to LED illumination. This work offered a promising method to rationally design for S/α-Fe2O3 in the environmental remediation.


Assuntos
Poluentes Ambientais , Enxofre , Sulfetos , Catálise
5.
J Immunol ; 211(7): 1134-1143, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37566486

RESUMO

Our group has previously demonstrated elevated serum-soluble ST2 in patients with active systemic lupus erythematosus, suggesting a role of IL-33 in the underlying pathogenesis. However, inconsistent results have been reported on the effect of exogenous IL-33 on murine lupus activity, which may be mediated by concerted actions of various immune cells in vivo. This study aimed to examine the function of IL-33 on macrophage polarization and regulatory T cells (Treg) and their interactive effects in the lupus setting by in vitro coculture experiments of macrophages and T cells that were performed in the presence or absence of IL-33-containing medium. Compared to IL-4-polarized bone marrow-derived macrophages (BMDM) from MRL/MpJ mice, adding IL-33 enhanced mRNA expression of markers of alternatively activated macrophages, including CD206 and Arg1. IL-33 and IL-4 copolarized BMDM produced higher TGF-ß but not IL-6 upon inflammatory challenge. These BMDM induced an increase in the Foxp3+CD25+ Treg population in cocultured allogeneic T cells from MRL/MpJ and predisease MRL/lpr mice. These copolarized BMDM also showed an enhanced suppressive effect on T cell proliferation with reduced IFN-γ and IL-17 release but increased TGF-ß production. In the presence of TGF-ß and IL-2, IL-33 also directly promoted inducible Treg that expressed a high level of CD25 and more sustained Foxp3. Unpolarized BMDM cocultured with these Treg displayed higher phagocytosis. In conclusion, TGF-ß was identified as a key cytokine produced by IL-4 and IL-33 copolarized alternatively activated macrophages and the induced Treg, which may contribute to a positive feedback loop potentiating the immunoregulatory functions of IL-33.


Assuntos
Lúpus Eritematoso Sistêmico , Linfócitos T Reguladores , Camundongos , Animais , Interleucina-33/metabolismo , Interleucina-4/metabolismo , Camundongos Endogâmicos MRL lpr , Macrófagos/patologia , Fator de Crescimento Transformador beta/metabolismo , Fatores de Transcrição Forkhead/metabolismo
6.
RSC Adv ; 13(13): 8720-8735, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36936847

RESUMO

The FeMoS2 catalyst for activating peroxymonosulfate (PMS) is a promising pathway for removing organic pollutants in wastewater, however, the dominant FeS2 phases and sulfur (S) vacancies in it are little involved. Herein, for the first time, novel bimetallic FeMoS2 microparticles were synthesized by a simple method and then applied for PMS activation for degrading organic pollutants. The catalysts were characterized by several techniques, including X-ray diffraction and X-ray photoelectron spectroscopies. The results revealed that new FeMoS2 microparticles containing S vacancies in the main FeS2 phases were obtained. FeS2 and S vacancies were found to play important roles for activating PMS by radical and nonradical pathways. More Fe2+ and Mo4+ were formed in the presence of S vacancies, which offered a new strategy for exploring novel heterogeneous catalysts in the activation of PMS for environmental remediation.

7.
J Innate Immun ; 15(1): 485-498, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36889298

RESUMO

The innate cytokine IL-33 is increasingly recognised to possess biological effects on various immune cells. We have previously demonstrated elevated serum level of soluble ST2 in patients with active systemic lupus erythematosus suggesting involvement of IL-33 and its receptor in the lupus pathogenesis. This study sought to examine the effect of exogenous IL-33 on disease activity of pre-disease lupus-prone mice and the underlying cellular mechanisms. Recombinant IL-33 was administered to MRL/lpr mice for 6 weeks, whereas control group received phosphate-buffered saline. IL-33-treated mice displayed less proteinuria, renal histological inflammatory changes, and had lower serum levels of pro-inflammatory cytokines including IL-6 and TNF-α. Renal tissue and splenic CD11b+ extracts showed features of M2 polarisation with elevated mRNA expression of Arg1, FIZZI, and reduced iNOS. These mice also had increased IL-13, ST2, Gata3, and Foxp3 mRNA expression in renal and splenic tissues. Kidneys of these mice displayed less CD11b+ infiltration, had downregulated MCP-1, and increased infiltration of Foxp3-expressing cells. Splenic CD4+ T cells showed increased ST2-expressing CD4+Foxp3+ population and reduced IFN-γ+ population. There were no differences in serum anti-dsDNA antibodies and renal C3 and IgG2a deposit in these mice. Exogenous IL-33 was found to ameliorate disease activity in lupus-prone mice with induction of M2 polarisation, Th2 response, and expansion of regulatory T cells. IL-33 likely orchestrated autoregulation of these cells through upregulation of ST2 expression.


Assuntos
Interleucina-33 , Lúpus Eritematoso Sistêmico , Linfócitos T Reguladores , Animais , Feminino , Camundongos , Complemento C3/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-33/farmacologia , Interleucina-33/uso terapêutico , Rim/metabolismo , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Proteínas Recombinantes/administração & dosagem , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
9.
RSC Adv ; 12(39): 25364-25376, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36275865

RESUMO

The enhancement of vacancies in catalysts involving Fenton-like reactions is a promising way to remove organic pollutants in wastewater, but sulfur vacancies are rarely involved. In this work, MoS2 containing defect sites were synthesized by a simple high-temperature treatment and then applied for activating peroxymonosulfate to eliminate organic pollutants in wastewater. The structure was characterized by several techniques such as XRD, BET, and XPS. Important influencing factors were systemically investigated. The results indicated that MoS2 with sulfur vacancies possessed a higher catalytic activity than that of the parent MoS2. The annealing temperature of the catalyst had a great effect on the removal of organic pollutants. Besides, the catalytic system had a wide pH range. Quenching and electron paramagnetic resonance (EPR) experiments indicated that the reaction system contained radical and non-radical species. The characterization results revealed that the defect sites in catalysts mainly strengthened the activity of catalysts. This study offers a new heterogeneous catalyst for the removal of organic pollutants via the peroxymonosulfate-based Fenton-like reactions.

10.
J Interv Card Electrophysiol ; 65(3): 663-673, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35864328

RESUMO

BACKGROUND: In this study, we aimed to investigate the role of miR-26a and miR-26b in the management of AF. METHODS: Real-time PCR was carried out to determine plasma microRNA expression in AF patients pre- and post-radiofrequency ablation. The correlation between the expression of SELP and miR-26a/miR-26b was also studied using luciferase assays to establish a miR-26a/miR-26b/SELP signaling pathway. RESULTS: The relative expression of SELP reached its peak in pre-ablation AF ( +) patients, while ablation treatment reduced the expression of SELP in AF ( +) patients. Similarly, AF pigs showed dysregulation of miR-26a/b and SELP, thus verifying the involvement of miR-26a/b and SELP in AF. Meanwhile, the regulatory association between SELP and miR-26a/b was also investigated, and the results showed that the presence of pre-miR-26a/b increased the levels of miR-26a/b and inhibited the mRNA/protein expression of SELP. Finally, using bioinformatic tools and luciferase assays, SELP mRNA was confirmed as the target of miR-26a/b, which affected the effect of AF ablation treatment. CONCLUSIONS: RFA helped to restore circulating levels of miR-26, which were reduced in atrial fibrillation. Meanwhile, miR-26 is a potential cause for the elevated plasma levels of pro-thrombogenic SELP in that disease.


Assuntos
Fibrilação Atrial , MicroRNAs , Animais , Suínos , Fibrilação Atrial/genética , Fibrilação Atrial/cirurgia , MicroRNAs/genética , RNA Mensageiro
11.
Bioorg Chem ; 122: 105719, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35272220

RESUMO

Acetolactate decarboxylase (ALDC) is a well-characterized catabolic enzyme catalyzes the decarboxylation of (±)-acetolactate to produce a single product, (R)-acetoin. It can also convert other racemic α-hydroxy-ß-ketoacids to corresponding α -hydroxyketones in R-configuration. In this work, we prepared ALDC of Streptococcus thermophilus (StALDC) and explored its stereoselectivity on different substrates. The enzyme displays no enantioselectivity on substrate (±)-acetolactate, but R-selectivity on product acetoin, which are identical with the data reported for various ALDCs. When compound (±)-2-propionyl-2-hydroxybutyrate is used as a substrate, however, the enzyme exhibits S-selectivity on both substrate and product, namely it can only decarboxylate (S)-2-propionyl-2-hydroxybutyrate to generate (S)-4-hydroxy-3-hexanone rather than its R-isomer, which is totally discriminate from the data published for the ALDC of Bacillus subtilis. As far as we know, this is the first time that substrate dependent enantioselectivity of ALDC is reported and the feature of StALDC is also discussed on the basis of homology modeling and molecular docking experiments.


Assuntos
Carboxiliases , Streptococcus thermophilus , Carboxiliases/química , Carboxiliases/metabolismo , Descarboxilação , Simulação de Acoplamento Molecular , Streptococcus thermophilus/metabolismo
12.
Zhen Ci Yan Jiu ; 47(2): 185-8, 2022 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-35218631

RESUMO

The position of Xuehai (SP10) is clear, but its locating method is vague, resulting in the disunity of clinical application and even possibly affecting the curative effect. Also, when learning the meridians and acupoints, the beginners are often confused by this issue possibly due to: ① when the bone-length proportional measurement combined with anatomic symbol (combination method) was adopted, it is not clear that the patient should take a posture of knee extension or knee flexion; ② when the combination method used, it is difficult to find the highest point of muscle eminence in the case of patient with thin vastus medialis muscle and fuzzy body surface projection; ③the simple method for locating SP10 is widely used at present, can it replace the combination method to locate this acupoint accurately?Guided by these questions, we, in the present paper, reviewed the rela-ted textbooks, works and other literature to explore the standard position of SP10, and the standard and simple methods for locating this acupoint. Comprehending various opinions, we hold that SP10 should be positioned under the extended knee posture, then, the acupoint's horizontal ordinate "2 cun superior to the medial end of the base of the patella" is determined by using bone-length proportional measurement to measure 2 cun from the bottom to the tip of the patella. Then, the body surface anatomic symbol method is used, when, the patient is asked to stretch the leg and contract the vastus medialis muscle, the highest spot of muscular eminence is the SP10. If the patient's muscular protuberance is not obvious, the middle line between the medial and lateral margins of the vastus medialis muscle is used as the vertical ordinate, and its intersection with the abscissa is SP10. The simple method is easy in operation and has a reference value, but may frequently produce errors, hence, it is not a substitution for the combination method.


Assuntos
Pontos de Acupuntura , Meridianos , Humanos
13.
Psychol Health Med ; 27(2): 333-342, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33877926

RESUMO

Fangcang hospitals, as tentative hospitals built to treat a huge turnover of patients with mild coronavirus disease 2019 (COVID-19) infections, have played a pivotal role to slow down the pandemic spread in China in 2020. However, anxiety and sleep disorders remain tough to address during the treatments. In this study, group psychological intervention in combination with pulmonary rehabilitation exercises were conducted in the trial group for the patients with mild COVID-19 infections in a Fangcang Hospital to mitigate the patients' anxiety and sleep disorders, while conventional nursing methods were done in the control group, with 70 randomly picked patients in each group. Effects were assessed through questionnaire method using state anxiety questionnaire (SAI) and Pittsburgh sleep quality index scale (PQSI) rating investigation. Results showed that both SAI and PSQI scores of the trial group were significantly lower than those of the control group (P < 0.05). The SAI scores of the trial group and the control group were 38.5 ± 13.2 and 45.8 ± 10.4 points (t = 3.600, P < 0.001), respectively, and the PSQI scores were 5.6 ± 3.0 and 7.1 ± 3.0 points (t = 2.982, P < 0.01), respectively. Our methods have significant advantages over conventional nursing methods to mitigate anxiety and sleep disorders for the patients with mild COVID-19 infections in the Fangcang Hospital.


Assuntos
COVID-19 , Transtornos do Sono-Vigília , Ansiedade/epidemiologia , Ansiedade/terapia , China/epidemiologia , Depressão/terapia , Terapia por Exercício , Hospitais , Humanos , Intervenção Psicossocial , SARS-CoV-2 , Sono , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/terapia
14.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 654-659, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821101

RESUMO

Objective: To investigate the effects and molecular mechanism of ropivacaine hydrochloride on osteosarcoma cell proliferation, invasion, and apoptosis. Methods: The osteosarcoma doxorubicin-resistant cell line (U2OS/DOX) was established by gradually increasing the drug doses. U2OS/DOX cells were treated with ropivacaine hydrochloride at the concentrations of 0, 20, 50 and 100 µg/ml, respectively; as different concentrations treatment groups of ropivacaine hydrochloride. pcDNA3.1 and pcDNA3.1-Livin were transfected into U2OS/DOX cells and then treated with 100 µg/ml ropivacaine hydrochloride, which were defined as ropivacaine hydrochloride 100 µg/ml+pcDNA3.1 group, ropivacaine hydrochloride 100 µg/ml+pcDNA3.1-Livin group. MTT was used to detect the cell proliferation inhibition rate and inhibitory concentration (IC50). Western blot was used to detect the expressions of cyclin-dependent kinase inhibitor 1A (P21) and activated cysteine aspartic protease-3 (Cleaved Caspase-3), E-cadherin, matrix metalloproteinase 2 (MMP-2) and Livin; clone formation experiments were used to detect the number of cell clones formed; flow cytometry was used to detect apoptosis; Transwell was used to detect cell migration and invasion; real-time fluorescent quantitative PCR (RT-qPCR) was used to detect Livin mRNA expression. Results: When the concentration of doxorubicin was more than 1 µg/ml, the proliferation inhibition rate of osteosarcoma cells U2OS was significantly increased in a concentration-dependent manner (P<0.05); when the concentration of doxorubicin was more than 10 µg/ml, the proliferation inhibition rate of osteosarcoma resistant cell U2OS/DOX was significantly increased, and it was dose-dependent (P<0.05). In U2OS/DOX cells treated with ropivacaine hydrochloride, the expressions of P21, Cleaved Caspase-3, and E-cadherin were increased significantly, the expression of MMP-2 was decreased significantly, the cell proliferation inhibition rate was increased significantly, the number of colony formation was decreased significantly, and the cells apoptosis rate was increased significantly, the number of cell migration and invasion was decreased significantly, and the expression of Livin was significantly reduced, in a concentration-dependent manner (P<0.05). Overexpression of Livin partially reversed the inhibitory effect of ropivacaine hydrochloride on proliferation, migration, invasion, and promotion effect on apoptosis of cell U2OS/DOX. Conclusion: Ropivacaine hydrochloride can significantly inhibit the proliferation, migration and invasion of doxorubicin-resistant osteosarcoma cells, and significantly promote osteoma cell apoptosis. The mechanism may be related to Livin.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Apoptose , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Metaloproteinase 2 da Matriz , Ropivacaina/farmacologia
15.
Int J Pharm ; 608: 121083, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34536524

RESUMO

Calcium supplementation is effective in alleviating the process of osteoporosis and the occurrence of osteoporotic fractures for people with long-term calcium deficiency. Herein, five water-stable calcium carboxylate compounds, that is, mononuclear coordination compound [Ca(Cbdcp)(H2O)6]·0.5H2O (1, H3CbdcpBr = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium bromide), and metal organic frameworks (MOFs) {[Ca3(Dcbdcp)2(H2O)12]·2H2O}n (2, H4DcbdcpBr = N-(3,5-dicarboxybenzyl)-(3,5-dicarboxyl)pyridinium bromide), {[Ca(Cmdcp)(H2O)4]·3H2O}n (3, H3CmdcpBr = N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide), {[Ca(Cdcbp)]·2H2O}n (4, H3CdcbpBr = 3-carboxyl-(3,5-dicarboxybenzyl)-pyridinium bromide) and {[Ca0.5(Cmcp)]·2H2O}n (5, H2CmcpBr = N-carboxymethyl-(3-carboxyl)pyridinium bromide), were synthesized from the reaction of CaCl2 with five different kinds of zwitterionic carboxylate ligands in the presence of NaOH, respectively. Compounds 1-5 were characterized by Fourier-transform infrared (FTIR) spectroscopy, elemental analyses, single-crystal X-ray crystallography, and inductively coupled plasma mass spectrometry (ICP-MS). Compound 1 features a mononuclear structure and MOF 2 with a one-dimensional (1D) structure while MOFs 3 and 5 with 2D layer structures and MOF 4 showing a 3D structure. Compounds 1-5 exhibited good water stability and possessed considerable biocompatibility with primary mice osteoblasts. The in vitro ability of compounds 1-5 in regulating osteoblastic differentiation was studied via alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, and quantitative real-time polymerase chain reaction (qPCR). Among these 5 compounds, MOF 4 showed the overall best in vitro osteogenic effects. Then, we administrated MOF 4 intragastrically to bilaterally ovariectomized mice for 8 weeks and found that bone loss caused by ovariectomy (OVX) was significantly alleviated. Besides, MOF 4 administration showed no toxic effects in the main organs of the mice. Altogether, zwitterionic carboxylate ligands-based calcium compounds provide a new strategy for calcium agents development.


Assuntos
Estruturas Metalorgânicas , Osteoporose , Animais , Cálcio , Ácidos Carboxílicos , Cristalografia por Raios X , Camundongos
16.
Biochimie ; 184: 72-87, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33607240

RESUMO

l-Valine, l-isoleucine, and l-leucine are three key proteinogenic amino acids, and they are also the essential amino acids required for mammalian growth, possessing important and to some extent, special physiological and biological functions. Because of the branched structures in their carbon chains, they are also named as branched-chain amino acids (BCAAs). This review will highlight the advance in studies of the enzymes involved in the biosynthetic pathway of BCAAs, concentrating on their chemical mechanisms and applications in screening herbicides and antibacterial agents. The uses of some of these enzymes in lab scale organic synthesis are also discussed.


Assuntos
Aminoácidos de Cadeia Ramificada/biossíntese , Vias Biossintéticas , Aminoácidos de Cadeia Ramificada/genética , Animais , Humanos
17.
J Autoimmun ; 116: 102562, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33168359

RESUMO

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10-14) and Asn in HLA-DRß1 position 37 (p = 5.12 × 10-11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10-14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10-13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10-9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.


Assuntos
Aminoácidos/genética , Predisposição Genética para Doença/genética , Cadeias alfa de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Polimorfismo de Nucleotídeo Único , Doença de Still de Início Tardio/genética , Adulto , Alelos , Povo Asiático/genética , China , Frequência do Gene , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla/métodos , Genótipo , Cadeias alfa de HLA-DQ/química , Cadeias HLA-DRB1/química , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Moleculares , Conformação Proteica , Doença de Still de Início Tardio/etnologia
18.
J Electrocardiol ; 63: 139-144, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33212414

RESUMO

OBJECTIVE: Clinical outcomes of patients with atrial fibrillation (AF) undergoing catheter ablation can be influenced by many factors. This study sought to investigate whether left atrial appendage (LAA) volume can predict the recurrence of AF after catheter ablation in hypertensive patients. METHODS: 108 hypertensive patients(aged 63.1 ± 8.1 years, 53.7% male) with paroxysmal or persistent AF undergoing a first catheter ablation were retrospectively evaluated. Contrast-enhanced cardiac computed tomography (CT) was performed in all enrolled patients prior to ablation for assessment of LAA volume and left atrium (LA) anatomy. Patients were followed up for 12 months to analyze the clinical outcomes after AF catheter ablation. RESULTS: 24 patients had AF recurrence after a mean follow-up of 12 months. Patients with AF recurrence (24, 22.2%) exhibited significantly larger (longer) LAA volume, LAA orifice area, LAA orifice short axis, LA volume, LA diameter and higher level of N-terminal proB-type natriuretic peptide (NT-proBNP) compared to those without AF recurrence. LAA volume correlated with type of AF, LA volume, LA diameter and the level of NT-proBNP. Multiple regression analysis demonstrated that LAA volume was an independent predictor of post-ablation AF recurrence in hypertensive patients. Furthermore, LAA volume > 9.99 ml served as a valuable independent predictor of AF recurrence, with a sensitivity of 83.3% and a specificity of 66.7% (area under the curve = 0.733). CONCLUSIONS: LAA volume derived from cardiac CT was an independent predictor of AF recurrence after catheter ablation in hypertensive patients.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Eletrocardiografia , Feminino , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
19.
Sci Rep ; 10(1): 15404, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958806

RESUMO

The large catalytic subunit of acetohydroxyacid synthase (AHAS, EC 2.2.1.6) of Thermotoga maritima (TmcAHAS) was prepared in this study. It possesses high specific activity and excellent stability. The protein and a whole cell catalyst overexpressing the protein were applied to the preparation of α-hydroxyketones including acetoin (AC), 3-hydroxy-2-pentanone (HP), and (R)-phenylacetylcarbinol (R-PAC). The results show that AC and HP could be produced in high yields (84% and 62%, respectively), while R-PAC could be synthesized in a high yield (about 78%) with an R/S ratio of 9:1. Therefore, TmcAHAS and the whole cell catalyst overexpressing the protein could be practically useful bio-catalysts in the preparation of α-hydroxyketones including AC, HP, and R-PAC. To the best of our knowledge, this is the first time that bacterial AHAS was used as a catalyst to prepare HP with a good yield, and also the first time that TmcAHAS was employed to synthesize AC and R-PAC.


Assuntos
Acetolactato Sintase/isolamento & purificação , Acetolactato Sintase/metabolismo , Catálise , Domínio Catalítico , Cetonas , Proteínas Recombinantes/isolamento & purificação , Thermotoga maritima/metabolismo
20.
CNS Neurosci Ther ; 26(5): 576-588, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31901155

RESUMO

AIMS: White matter hyperintensity (WMH) is the most common neuroimaging manifestation of cerebral small vessel disease and is related to cognitive dysfunction or dementia. This study aimed to investigate the mechanism and effective indicators to predict WMH-related cognitive impairment. METHODS: We recruited 22 healthy controls (HC), 25 cases of WMH with normal cognition (WMH-NC), and 23 cases of WMH with mild cognitive impairment (WMH-MCI). All individuals underwent diffusion tensor imaging (DTI) and a standardized neuropsychological assessment. Automated Fiber Quantification was used to extract altered DTI metrics between groups, and partial correlation was performed to assess the associations between WM integrity and cognitive performance. Furthermore, machine learning analyses were performed to determine underlying imaging markers of WMH-related cognitive impairment. RESULTS: Our study found that mean diffusivity (MD) values of several fiber bundles including the bilateral anterior thalamic radiation (ATR), the left inferior fronto-occipital fasciculus (IFOF), the right inferior longitudinal fasciculus (ILF), and the right superior longitudinal fasciculus (SLF) were negatively correlated with memory function, while that of the anterior component of the right IFOF and the posterior and intermediate component of the right ILF showed significant negative correlation with MMSE and episodic memory, respectively. Furthermore, machine learning analyses showed that the accuracy of recognizing WMH-MCI patients from the WMH populations was up to 80.5% and the intermediate and posterior components of the right ILF and the anterior component of the right IFOF contribute the most. CONCLUSIONS: Changes in the properties of DTI may be the potential mechanism of WMH-related MCI, especially the right IFOF and the right ILF, which may become imaging markers for predicting WMH-related cognitive dysfunction.


Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Lobo Frontal/diagnóstico por imagem , Lobo Occipital/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
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