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1.
J Org Chem ; 89(14): 9755-9768, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38935873

RESUMO

A nickel-catalyzed direct sulfonylation of alkenes with sulfonyl chlorides has been developed using 1,10-phenanthroline-5,6-dione as the ligand. Unactivated alkenes and styrenes including 1,1-, 1,2-disubstituted alkenes can be subjected to the protocol, and a wide range of vinyl sulfones was obtained in high to excellent yields with good functional group compatibility. Notably, the process did not allow the desulfonylation of sulfonyl chloride or chlorosulfonylation of alkenes. Radical-trapping experiment supported that a sulfonyl free-radical was likely produced and triggered subsequent transformation in the process.

2.
Acta Pharmacol Sin ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926478

RESUMO

Somatostatin receptor 5 (SSTR5) is highly expressed in ACTH-secreting pituitary adenomas and is an important drug target for the treatment of Cushing's disease. Two cyclic SST analog peptides (pasireotide and octreotide) both can activate SSTR5 and SSTR2. Pasireotide is preferential binding to SSTR5 than octreotide, while octreotide is biased to SSTR2 than SSTR5. The lack of selectivity of both pasireotide and octreotide causes side effects, such as hyperglycemia, gastrointestinal disturbance, and abnormal glucose homeostasis. However, little is known about the binding and selectivity mechanisms of pasireotide and octreotide with SSTR5, limiting the development of subtype-selective SST analog drugs specifically targeting SSTR5. Here, we report two cryo-electron microscopy (cryo-EM) structures of SSTR5-Gi complexes activated by pasireotide and octreoitde at resolutions of 3.09 Å and 3.24 Å, respectively. In combination with structural analysis and functional experiments, our results reveal the molecular mechanisms of ligand recognition and receptor activation. We also demonstrate that pasireotide preferentially binds to SSTR5 through the interactions between Tyr(Bzl)/DTrp of pasireotide and SSTR5. Moreover, we find that the Q2.63, N6.55, F7.35 and ECL2 of SSTR2 play a crucial role in octreotide biased binding of SSTR2. Our results will provide structural insights and offer new opportunities for the drug discovery of better selective pharmaceuticals targeting specific SSTR subtypes.

3.
BMC Oral Health ; 24(1): 55, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195496

RESUMO

BACKGROUND: Ameloblastoma, a common benign tumor found in the jaw bone, necessitates accurate localization and segmentation for effective diagnosis and treatment. However, the traditional manual segmentation method is plagued with inefficiencies and drawbacks. Hence, the implementation of an AI-based automatic segmentation approach is crucial to enhance clinical diagnosis and treatment procedures. METHODS: We collected CT images from 79 patients diagnosed with ameloblastoma and employed a deep learning neural network model for training and testing purposes. Specifically, we utilized the Mask R-CNN neural network structure and implemented image preprocessing and enhancement techniques. During the testing phase, cross-validation methods were employed for evaluation, and the experimental results were verified using an external validation set. Finally, we obtained an additional dataset comprising 200 CT images of ameloblastoma from a different dental center to evaluate the model's generalization performance. RESULTS: During extensive testing and evaluation, our model successfully demonstrated the capability to automatically segment ameloblastoma. The DICE index achieved an impressive value of 0.874. Moreover, when the IoU threshold ranged from 0.5 to 0.95, the model's AP was 0.741. For a specific IoU threshold of 0.5, the model achieved an AP of 0.914, and for another IoU threshold of 0.75, the AP was 0.826. Our validation using external data confirms the model's strong generalization performance. CONCLUSION: In this study, we successfully applied a neural network model based on deep learning that effectively performs automatic segmentation of ameloblastoma. The proposed method offers notable advantages in terms of efficiency, accuracy, and speed, rendering it a promising tool for clinical diagnosis and treatment.


Assuntos
Ameloblastoma , Aprendizado Profundo , Humanos , Ameloblastoma/diagnóstico por imagem , Projetos de Pesquisa , Tomografia Computadorizada por Raios X
4.
J Org Chem ; 88(19): 13825-13837, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37737590

RESUMO

A metal-free selective ortho-C-H amidation of aryl iodines(III) with the use of N-methoxy amides as aminating reagents under mild conditions is described here. In the protocol, excellent chemoselectivity and high regioselectivity were obtained. Notably, the iodine substituent rendered the amidation product suitable to be used for further elaboration.

5.
J Org Chem ; 87(21): 14194-14207, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36265020

RESUMO

An acyl lactonization of alkenes with aldehydes under visible-light photoredox catalysis is described. With the protocol, a broad scope of alkenoic acids and aldehydes could be compatible and good functional group tolerance is obtained. A series of acyl lactones are obtained with isolated yields ranging from 50-95%. Mechanistic studies revealed that the transformation should proceed via a radical chain process.


Assuntos
Aldeídos , Alcenos , Lactonas , Estrutura Molecular , Catálise
6.
Int J Clin Pract ; 2022: 3882975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36474552

RESUMO

Objective: This study aims to compare the effect of blended teaching and traditional teaching in higher medical education during the pandemic era. Methods: Taking the teaching of neurology as an example, 293 Yangzhou University Clinical Medicine 2016 undergraduate students were selected as the research subjects, and were randomly divided into 2 groups a blended teaching group (n = 148) and a traditional teaching group (n = 145), and received blended teaching and traditional teaching, respectively. The blended teaching was based on a Massive Open Online Course, problem-based learning, and case-based learning and supplemented by Tencent video conferences, QQ messaging groups, and other auxiliary teaching tools. At the end of the course, the teaching effect and satisfaction rate were evaluated through theory assessment, practical skills assessment, and an anonymous questionnaire survey. Results: There were significant differences in theoretical achievements (81.83 ± 6.23 vs 76.79 ± 6.87, P < 0.001) and practical skill achievements (84.74 ± 6.50 vs 78.48 ± 6.53, P < 0.001). In addition, significant differences in all aspects of satisfaction rate were observed between the two groups (all P < 0.001). Conclusion: Blended teaching is beneficial to students' learning and stimulates their enthusiasm, cultivates clinical thinking ability, and improves teaching quality. Thus, it has played a positive role in the reform of higher medical teaching during the pandemic era.


Assuntos
Educação Médica , Humanos
7.
Bull Environ Contam Toxicol ; 106(1): 92-98, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33392688

RESUMO

Cadmium (Cd) threatens rice quality and human health, yet this risk remains uncertain in paddy fields with high geological background of transportation and deposition. In this study, we collected 31 pairs of soil and rice grain samples in Doumen and Xinhui Districts in Guangdong province, China and investigated which factors controlled Cd bioavailability in soil and accumulation in rice. Soil samples were mostly acidic and contained a range of organic matter. Total Cd in soil varied from 0.10 to 1.03 mg kg- 1 and was positively correlated with those of calcium (Ca), manganese (Mn) and iron (Fe), suggesting that these elements shared same sources and Cd was most likely originated from parent material. The activity ratio (AR, CaCl2-extractable Cd/soil Cd) and bioconcentration factor (BCF, rice grain Cd/soil Cd) of Cd were negatively correlated with soil pH. The coupling relationship between soil and rice grain Cd could be described by a linear model, which was used to predict soil Cd threshold values to keep rice grain Cd concentration from exceeding the Chinese limit (0.2 mg kg- 1). In summary, Cd pollution was not very severe in the paddy soils of studied area but the risk could not be neglected when soil was acidified, which could increase Cd bioavailability and accumulation in rice grain.


Assuntos
Oryza , Poluentes do Solo , Disponibilidade Biológica , Cádmio/análise , Cálcio , China , Humanos , Concentração de Íons de Hidrogênio , Solo , Poluentes do Solo/análise
8.
J Biol Chem ; 294(35): 12947-12956, 2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31296659

RESUMO

Natural killer T (NKT) cells are a subset of T lymphocytes that recognize glycolipid antigens presented by the CD1d molecule (CD1d). They rapidly respond to antigen challenge and can activate both innate and adaptive immune cells. To study the role of antigen presentation in NKT cell activation, previous studies have developed several anti-CD1d antibodies that block CD1d binding to T-cell receptors (TCRs). Antibodies that are specific to both CD1d and the presented antigen can only be used to study the function of only a limited number of antigens. In contrast, antibodies that bind CD1d and block TCR binding regardless of the presented antigen can be widely used to assess the role of TCR-mediated NKT cell activation in various disease models. Here, we report the crystal structure of the widely used anti-mouse CD1d antibody 1B1 bound to CD1d at a resolution of 2.45 Å and characterized its binding to CD1d-presented glycolipids. We observed that 1B1 uses a long hydrophobic H3 loop that is inserted deep into the binding groove of CD1d where it makes intimate nonpolar contacts with the lipid backbone of an incorporated spacer lipid. Using an NKT cell agonist that has a modified sphingosine moiety, we further demonstrate that 1B1 in its monovalent form cannot block TCR-mediated NKT cell activation, because 1B1 fails to bind with high affinity to mCD1d. Our results suggest potential limitations of using 1B1 to assess antigen recognition by NKT cells, especially when investigating antigens that do not follow the canonical two alkyl-chain rule.


Assuntos
Anticorpos Monoclonais/imunologia , Antígenos CD1d/imunologia , Células T Matadoras Naturais/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Animais , Reações Antígeno-Anticorpo , Antígenos CD1d/isolamento & purificação , Camundongos , Receptores de Antígenos de Linfócitos T/química , Células Tumorais Cultivadas
9.
J Biol Chem ; 294(39): 14345-14356, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31391251

RESUMO

Type I natural killer T (NKT) cells are a population of innate like T lymphocytes that rapidly respond to α-GalCer presented by CD1d via the production of both pro- and anti-inflammatory cytokines. While developing novel α-GalCer analogs that were meant to be utilized as potential adjuvants because of their production of pro-inflammatory cytokines (Th1 skewers), we generated α-galactosylsphingamides (αGSA). Surprisingly, αGSAs are not potent antigens in vivo despite their strong T-cell receptor (TCR)-binding affinities. Here, using surface plasmon resonance (SPR), antigen presentation assays, and X-ray crystallography (yielding crystal structures of 19 different binary (CD1d-glycolipid) or ternary (CD1d-glycolipid-TCR) complexes at resolutions between 1.67 and 2.85 Å), we characterized the biochemical and structural details of αGSA recognition by murine NKT cells. We identified a molecular switch within murine (m)CD1d that modulates NKT cell activation by αGSAs. We found that the molecular switch involves a hydrogen bond interaction between Tyr-73 of mCD1d and the amide group oxygen of αGSAs. We further established that the length of the acyl chain controls the positioning of the amide group with respect to the molecular switch and works synergistically with Tyr-73 to control NKT cell activity. In conclusion, our findings reveal important mechanistic insights into the presentation and recognition of glycolipids with polar moieties in an otherwise apolar milieu. These observations may inform the development αGSAs as specific NKT cell antagonists to modulate immune responses.


Assuntos
Antígenos CD1d/química , Glicoesfingolipídeos/química , Células Matadoras Naturais/imunologia , Simulação de Dinâmica Molecular , Animais , Antígenos CD1d/metabolismo , Sítios de Ligação , Glicoesfingolipídeos/metabolismo , Ligação de Hidrogênio , Ativação Linfocitária , Camundongos , Oxigênio/química , Ligação Proteica , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/metabolismo , Células Sf9 , Spodoptera
10.
J Biol Chem ; 292(13): 5262-5270, 2017 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-28179428

RESUMO

Peptide antigen presentation by major histocompatibility complex (MHC) class I proteins initiates CD8+ T cell-mediated immunity against pathogens and cancers. MHC I molecules typically bind peptides with 9 amino acids in length with both ends tucked inside the major A and F binding pockets. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zigzag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from Toxoplasma gondii bound by HLA-A*02:01. These peptides were extended at the C terminus (PΩ) and contained charged amino acids not more than 3 residues after the anchor amino acid at PΩ, which enabled them to open the F pocket and expose their C-terminal extension into the solvent. Here, we show that the mechanism of F pocket opening is dictated by the charge of the first charged amino acid found within the extension. Although positively charged amino acids result in the Tyr-84 swing, amino acids that are negatively charged induce a not previously described Lys-146 lift. Furthermore, we demonstrate that the peptides with alternative binding modes have properties that fit very poorly to the conventional MHC class I pathway and suggest they are presented via alternative means, potentially including cross-presentation via the MHC class II pathway.


Assuntos
Apresentação de Antígeno/imunologia , Antígeno HLA-A2/imunologia , Alelos , Aminoácidos , Sítios de Ligação , Antígeno HLA-A2/metabolismo , Antígenos de Histocompatibilidade Classe II , Humanos , Peptídeos/imunologia , Ligação Proteica , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo , Toxoplasma/imunologia
11.
Plant Mol Biol ; 96(3): 245-263, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29344831

RESUMO

KEY MESSAGE: We defined a comprehensive core ABA signaling network in monocot maize, including the gene expression, subcellular localization and interaction network of ZmPYLs, ZmPP2Cs, ZmSnRK2s and the putative substrates. The phytohormone abscisic acid (ABA) plays an important role in plant developmental processes and abiotic stress responses. In Arabidopsis, ABA is sensed by the PYL ABA receptors, which leads to binding of the PP2C protein phosphatase and activation of the SnRK2 protein kinases. These components functioning diversely and redundantly in ABA signaling are little known in maize. Using Arabidopsis pyl112458 and snrk2.2/3/6 mutants, we identified several ABA-responsive ZmPYLs and ZmSnRK2s, and also ZmPP2Cs. We showed the gene expression, subcellular localization and interaction network of ZmPYLs, ZmPP2Cs, and ZmSnRK2s, and the isolation of putative ZmSnRK2 substrates by mass spectrometry in monocot maize. We found that the ABA dependency of PYL-PP2C interactions is contingent on the identity of the PP2Cs. Among 238 candidate substrates for ABA-activated protein kinases, 69 are putative ZmSnRK2 substrates. Besides homologs of previously reported putative AtSnRK2 substrates, 23 phosphoproteins have not been discovered in the dicot Arabidopsis. Thus, we have defined a comprehensive core ABA signaling network in monocot maize and shed new light on ABA signaling.


Assuntos
Ácido Abscísico/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Transdução de Sinais , Zea mays/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Mapas de Interação de Proteínas , Zea mays/genética , Zea mays/crescimento & desenvolvimento
12.
BMC Health Serv Res ; 18(1): 821, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30373577

RESUMO

BACKGROUND: Rapid demographic and economic changes have made chronic disease the number one health issue in China, contributing to more than 80% of the country's 10.3 million annual deaths and nearly 70% of its total disease burden (Wang et al., Toward a Healthy and Harmonious Life in China: Stemming the Rising Tide of Non-Communicable Diseases, 2011; Yip and Hsiao, Lancet 384: 805-18, 2014). Diabetes is a major contributor to the chronic disease burden and is experienced by nearly 11% of the adult population of China (Yang et al., N Engl J Med 362:1090-101, 2010). In response to the challenges of chronic disease, the Chinese government initiated comprehensive health care reforms nationwide in 2009. A key measure was a hierarchical diagnosis and treatment system for monitoring and reducing chronic diseases and improving the community health service system (Barber et al., Health Policy Plan 29:367-78, 2014). Primary hospitals, such as community health service centers, are the main gatekeepers for management of diabetes and other chronic diseasesin China. In recognition of the need for a more patient-centered approach, the Chinese government has piloted a program incorporating methods of diabetes self-management for chronic care: the Happy Life Club (Browning et al., Front in Public Health 2:181, 2015). This program is modeled on a similar program developed in Australia (Kelly et al., Aust J Prim Health 9:186-9, 2003). The ICDMS is an important tool in the implementation of patient-centered programs targeting chronic health issues, and its success is determined by factors, such as frequent contact between patients and doctors and effective website training for patients. This retrospective study used de-identified data from the Fangzhuang (Beijing) intelligent chronic disease management system (ICDMS) database to evaluate the effect of an intelligent chronic disease management system on selected Beijing community patients who have type 2 diabetes mellitus (T2DM). METHODS: A comparative study before and after ICDMS implementation was performed to evaluate the effect of ICDMS on the rates of follow-up and laboratory examinations, measurement rates of blood glucose and lipids, glycosylated hemoglobin (HbA1c) and blood lipid levels, as well as the corresponding health parameters. Continuous variables and categorical variables were analyzed using paired t-test and McNemar's tests, respectively. RESULTS: A total of 2451 T2DM patients met inclusion/exclusion criteria. Compared with the pre-index period, the laboratory examination, rates of blood glucose and blood lipids increased significantly in the post-index period (p < 0.001). Triglyceride (TC) levels decreased significantly from 5.22 mmol/L to 5.11 mmol/L (p < 0.05), and high density lipoprotein-cholesterol (HDL-C) levels increased significantly from 1.35 mmol/L to 1.48 mmol/L (p < 0.05). The control rate of TC increased from 24.86 to 29.76% (p = 0.079). The control rate of low density lipoprotein-cholesterol (LDL-C) increased from 12.16 to 13.97% (p = 0.421), while the control rate of HDL-C increased significantly from 68.60 to 78.77%. Importantly, Compared with the patients with HbA1C above 7% in the pre-index period, the mean HbA1c decreased significantly from 7.84 to 6.94%((p < 0.001) in the post-index period, and the control rate of HbA1c was 57.43%. CONCLUSIONS: The intelligent chronic disease management system is an effective tool in the management of T2DM and should be promoted by the Community Health Service Center in China as well as in other developing countries.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Adolescente , Adulto , Idoso , Pequim , Glicemia/metabolismo , China , LDL-Colesterol/metabolismo , Doença Crônica , Serviços de Saúde Comunitária , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
13.
Mycopathologia ; 183(3): 551-558, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29335843

RESUMO

OBJECTIVE: To improve the diagnosis and treatment of Penicilliosis marneffei without human immunodeficiency virus infection. METHODS: Analyze and review the clinical features, diagnosis and treatment of six cases of P. marneffei without human immunodeficiency virus infection at The First Affiliated Hospital of Fujian Medical University. RESULTS: Two cases were diagnosed in the ENT Department, three cases in the respiratory department and one case in the dermatological department. Penicillium marneffei infection was confirmed by sputum culture, blood culture and tissue biopsy. After definite diagnosis, one refused further treatment, and others showed significant improvement. CONCLUSION: Penicilliosis marneffei is insidious onset and easy to be escaped and misdiagnosed. To achieve early diagnosis and appropriate treatment, doubtful cases should be alerted for the diagnoses as P. marneffei.


Assuntos
Micoses/diagnóstico , Micoses/patologia , Talaromyces/isolamento & purificação , Adulto , Biópsia , Sangue/microbiologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Técnicas Microbiológicas , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/microbiologia , Nasofaringe/patologia , Prognóstico , Escarro/microbiologia , Tomografia Computadorizada por Raios X , Adulto Jovem
14.
Neurochem Res ; 42(10): 2841-2849, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28508993

RESUMO

Neuronal apoptosis mediated by the mitochondrial apoptosis pathway is an important pathological process in cerebral ischemia-reperfusion injury. 14,15-EET, an intermediate metabolite of arachidonic acid, can promote cell survival during ischemia/reperfusion. However, whether the mitochondrial apoptotic pathway is involved this survival mechanism is not fully understood. In this study, we observed that infarct size in ischemia-reperfusion injury was reduced in sEH gene knockout mice. In addition, Caspase 3 activation, cytochrome C release and AIF nuclear translocation were also inhibited. In this study, 14,15-EET pretreatment reduced neuronal apoptosis in the oxygen-glucose deprivation and re-oxygenation group in vitro. The mitochondrial apoptosis pathway was also inhibited, as evidenced by AIF translocation from the mitochondria to nucleus and the reduction in the expressions of cleaved-caspase 3 and cytochrome C in the cytoplasm. 14,15-EET could reduce neuronal apoptosis through upregulation of the ratio of Bcl-2 (anti-apoptotic protein) to Bax (apoptosis protein) and inhibition of Bax aggregation onto mitochondria. PI3K/AKT pathway is also probably involved in the reduction of neuronal apoptosis by EET. Our study suggests that 14,15-EET could suppress neuronal apoptosis and reduce infarct volume through the mitochondrial apoptotic pathway. Furthermore, the PI3K/AKT pathway also appears to be involved in the neuroprotection against ischemia-reperfusion by 14,15-EET.


Assuntos
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Ácido 8,11,14-Eicosatrienoico/farmacologia , Animais , Apoptose/fisiologia , Citocromos c/efeitos dos fármacos , Citocromos c/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/fisiologia
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(6): 558-63, 2016 Jun.
Artigo em Zh | MEDLINE | ID: mdl-27324547

RESUMO

OBJECTIVE: To investigate the influence of cefuroxime sodium (CS) on the electrophysiological function of cerebellar Purkinje cells (PCs) in Sprague-Dawley rats. METHODS: Postnatal day 7 (P7) Sprague-Dawley rats were divided into early administration I and II groups (administered from P7 to P14) and late administration group (administered from P14 to P21), and all the groups received intraperitoneally injected CS. The control groups for early and late administration groups were also established and treated with intraperitoneally injected normal saline of the same volume. There were 10 rats in each group. The rats in the early administration I group and early administration control group were sacrificed on P15, and those in the early administration II group, late administration group, and late administration control group were sacrificed on P22. The whole-cell patch-clamp technique was used to record inward current and action potential of PCs on cerebellar slices, as well as the long-term depression (LTD) of excitatory postsynaptic current (EPSC) in PCs induced by low-frequency stimulation of parallel fiber (PF). RESULTS: Compared with the control groups, the early and late administration groups had a slightly higher magnitude of inward current and a slightly higher amplitude of action potential of PCs (P>0.05). All administration groups had a significantly higher degree of EPSC inhibition than the control groups (P<0.01), and the early administration II group had a significantly greater degree of EPSC inhibition than the late administration group (P<0.01). CONCLUSIONS: Early CS exposure after birth affects the synaptic plasticity of PF-PCs in the cerebellum of young rats, which persists after drug withdrawal.


Assuntos
Antibacterianos/farmacologia , Cefuroxima/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Células de Purkinje/efeitos dos fármacos , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Células de Purkinje/fisiologia , Ratos , Ratos Sprague-Dawley
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(1): 85-93, 2016 Jan.
Artigo em Zh | MEDLINE | ID: mdl-26781419

RESUMO

OBJECTIVE: To investigate the protective effect of succinic acid (SA) on the cerebellar Purkinje cells (PCs) of neonatal rats with convulsion. METHODS: A total of 120 healthy neonatal Sprague-Dawley rats aged 7 days were randomly divided into a neonatal period group and a developmental period group. Each of the two groups were further divided into 6 sub-groups: normal control, convulsion model, low-dose phenobarbital (PB) (30 mg/kg), high-dose PB (120 mg/kg), low-dose SA (30 mg/kg), and high-dose SA (120 mg/kg). Intraperitoneal injection of pentylenetetrazole was performed to establish the convulsion model. The normal control group was treated with normal saline instead. The rats in the neonatal group were sacrificed at 30 minutes after the injection of PB, SA, or normal saline, and the cerebellum was obtained. Those in the developmental group were sacrificed 30 days after the injection of PB, SA, or normal saline, and the cerebellum was obtained. Whole cell patch clamp technique was used to record the action potential (AP) of PCs in the cerebellar slices of neonatal rats; the parallel fibers (PF) were stimulated at a low frequency to induce excitatory postsynaptic current (EPSC). The effect of SA on long-term depression (LTD) of PCs was observed. RESULTS: Compared with the normal control groups, the neonatal and developmental rats with convulsion had a significantly higher AP frequency of PCs (P<0.05), and the developmental rats with convulsion had a significantly decreased threshold stimulus (P<0.01) and a significantly greater inhibition of the amplitude of EPSC in PCs (P<0.05). Compared with the normal control groups, the neonatal and developmental rats with convulsion in the high-dose PB groups had a significantly decreased threshold stimulus (P<0.01), a significantly higher AP frequency of PCs (P<0.05), and a significantly greater inhibition of EPSC in PCs (P<0.05). Compared with the neonatal and developmental rats in the convulsion model groups, those in the high-dose SA groups had a significantly decreased AP frequency of PCs (P<0.05). The developmental rats in the low- and high-dose SA groups had a significantly higher AP threshold than those in the convulsion model group (P<0.05). CONCLUSIONS: The high excitability of PCs and the abnormal PF-PC synaptic plasticity caused by convulsion in neonatal rats may last to the developmental period, which can be aggravated by PB, while SA can reduce the excitability of PCs in neonatal rats with convulsion and repair the short- and long-term abnormalities of LTD of PCs caused by convulsion.


Assuntos
Citoproteção , Células de Purkinje/efeitos dos fármacos , Convulsões/tratamento farmacológico , Ácido Succínico/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Células de Purkinje/fisiologia , Ratos , Ratos Sprague-Dawley , Convulsões/fisiopatologia
17.
Biochem Genet ; 52(11-12): 474-93, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25027834

RESUMO

Microarray assay of four inbred lines was used to identify 303 microRNAs differentially expressed under drought stress. The microRNAs were used for bioinformatics prediction of their target genes. The majority of the differentially expressed microRNA families showed different expression profiles at different time points of the stress process among the four inbred lines. Digital gene expression profiling revealed 54 genes targeted by 128 of the microRNAs differentially expressed under the same stress conditions. The differential expression of miR159 and miR168 was further validated by locked nucleic acid northern hybridization. These results indicated that miR159 and miR168, as well as numerous other microRNAs, play critical roles in signaling pathways of maize response to drought stress. However, the level of the post-transcriptional regulation mediated by microRNAs had different responses among genotypes, and the gene expression related to signaling pathways under drought stress is also regulated, possibly by multiple mechanisms.


Assuntos
Secas , MicroRNAs/genética , Estresse Fisiológico , Transcriptoma , Zea mays/genética , Regulação da Expressão Gênica de Plantas , MicroRNAs/metabolismo , Transdução de Sinais , Zea mays/metabolismo
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(4): 1056-9, 2014 Apr.
Artigo em Zh | MEDLINE | ID: mdl-25007628

RESUMO

A method for on-line monitoring the dissolution of Valsartan and hydrochlorothiazide tablets assisted by mathematical separation model of linear equations was established. UV spectrums of valsartan and hydrochlorothiazide were overlapping completely at the maximum absorption wavelength respectively. According to the Beer-Lambert principle of absorbance additivity, the absorptivity of Valsartan and hydrochlorothiazide was determined at the maximum absorption wavelength, and the dissolubility of Valsartan and hydrochlorothiazide tablets was detected by fiber-optic dissolution test (FODT) assisted by the mathematical separation model of linear equations and compared with the HPLC method. Results show that two ingredients were real-time determined simultaneously in given medium. There was no significant difference for FODT compared with HPLC (p > 0.05). Due to the dissolution behavior consistency, the preparation process of different batches was stable and with good uniformity. The dissolution curves of valsartan were faster and higher than hydrochlorothiazide. The dissolutions at 30 min of Valsartan and hydrochlorothiazide were concordant with US Pharmacopoeia. It was concluded that fiber-optic dissolution test system assisted by the mathematical separation model of linear equations that can detect the dissolubility of Valsartan and hydrochlorothiazide simultaneously, and get dissolution profiles and overall data, which can directly reflect the dissolution speed at each time. It can provide the basis for establishing standards of the drug. Compared to HPLC method with one-point data, there are obvious advantages to evaluate and analyze quality of sampling drug by FODT.


Assuntos
Hidroclorotiazida/análise , Tetrazóis/análise , Valina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Modelos Teóricos , Solubilidade , Comprimidos , Valina/análise , Valsartana
19.
Int J Rheum Dis ; 27(1): e14863, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37564026

RESUMO

An increasing number of cases have reported that coronavirus disease 2019 (COVID-19) can lead to immune system dysregulation and induce autoimmune diseases, but the mechanism is unclear. We treated a patient who presented with an unknown fever after infection with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2023. After excluding the possibility of infection, malignancy, and other connective tissue diseases, we considered the diagnosis of IgG4-related disease in consideration of the patient's pathology and clinical findings. In this article, we summarize our diagnostic experience and summarize the case reports of IgG4-related diseases associated with SARS-CoV-2 infections since the COVID-19 pandemic.


Assuntos
COVID-19 , Doenças do Tecido Conjuntivo , Doença Relacionada a Imunoglobulina G4 , Humanos , COVID-19/complicações , COVID-19/diagnóstico , SARS-CoV-2 , Pandemias , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico
20.
Int J Biol Macromol ; 266(Pt 1): 131208, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552695

RESUMO

In this study, three activators and two activation methods were employed to activate sesame lignin-based biochar. The biochar samples were comprehensively characterized, their abilities to adsorb benzo[a]pyrene (BaP) from sesame oil were assessed, and the mechanism was analyzed. The results showed that the biochar obtained by one-step activation was more effective in removing BaP from sesame oil than the biochar produced by two-step activation. Among them, the biochar generated by one-step activation with ZnCl2 as the activator had the largest specific surface area (1068.8776 m3/g), and the richest mesoporous structure (0.7891 m3/g); it removed 90.53 % of BaP from sesame oil. BaP was mainly adsorbed by the mesopores of biochar. Mechanistically, pore-filling, π-π conjugations, hydrogen bonding, and n-π interactions were involved. The adsorption was spontaneous and heat-absorbing. In conclusion, the preparation of sesame lignin biochar using one-step activation with ZnCl2 as the activator was found to be the best for removing BaP from sesame oil. This biochar may be an economical adsorbent for the industrial removal of BaP from sesame oil.


Assuntos
Benzo(a)pireno , Carvão Vegetal , Lignina , Óleo de Gergelim , Sesamum , Carvão Vegetal/química , Lignina/química , Benzo(a)pireno/química , Adsorção , Óleo de Gergelim/química , Sesamum/química , Compostos de Zinco/química , Cloretos/química
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