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OBJECTIVE: This study aimed to investigate the effect of psychological intervention on the visual quality of patients with a diffractive multifocal intraocular lens implant and its possible mechanism. METHODS: Eighty-nine patients undergoing age-related cataract surgery were enrolled in the study at the Affiliated Hospital of Southwest Medical University between December 2015 and July 2017. They were randomly divided into two groups: multiple focus M1 group (n = 45) and multiple focus M2 group (n = 40). The M1 group was only given routine preoperative health education, treatment, and evaluation, while the M2 group also received psychological intervention. RESULTS: After treatment, there was no statistical difference in the uncorrected distance and near visual acuity, corrected distance and near visual acuity, or the vision and near removal rate in either of the two groups (p > 0.05). However, postoperative glare was lower in the M2 group (p < 0.05), and patient satisfaction was higher in the M2 group (p < 0.05). The M2 group had a more obvious improvement in the Symptom Checklist-90 score (p < 0.05), the serum interleukin-6 (IL-6) was lower, and the serum brain-derived neurotrophic factor (BDNF) was higher in the M2 group (p < 0.05). In addition, serum IL-6 had a negative correlation with the depression score, and serum BDNF also showed a negative correlation with the anxiety score (p < 0.05). CONCLUSIONS: Psychological intervention improved the stress state of patients with age-related cataracts and diffractive multifocal intraocular lens implants, reduced the level of inflammatory factors in the body, improved the level of BDNF, reduced postoperative visual interference, and improved postoperative satisfaction.
Assuntos
Catarata , Lentes Intraoculares , Lentes Intraoculares Multifocais , Facoemulsificação , Humanos , Implante de Lente Intraocular , Fator Neurotrófico Derivado do Encéfalo , Interleucina-6 , Intervenção Psicossocial , Sensibilidades de Contraste , Estudos Prospectivos , Catarata/diagnóstico , Catarata/terapia , Catarata/etiologia , Satisfação do Paciente , Desenho de PróteseRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. METHODS: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). The serodiagnostic power of the specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and consistency rate. RESULTS: The seroconversion of specific IgM and IgG antibodies were observed as early as the fourth day after symptom onset. In the patients with confirmed COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, respectively, and those of IgG were 83.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, respectively, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 and rely on great specificity. CONCLUSIONS: The antibodies against SARS-CoV-2 can be detected in the middle and later stages of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.
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Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pneumonia Viral/diagnóstico , Adulto , Idoso , Betacoronavirus/imunologia , COVID-19 , Teste para COVID-19 , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Sensibilidade e Especificidade , Fatores de TempoRESUMO
The natural city, which is essential to understand urban physical scale and identify urban sprawling in urban studies, represents the urban functional boundaries of the city defined by human activities rather than the administrative boundaries. Most studies tend to utilize physical environment data such as street networks and remote sensing data to delimitate the natural city, however, such data may not match the real distribution of human activity density in the new cities or even ghost cities in China. This paper suggests aggregating the natural city boundary from the service area polygons of points of interest based on Reilly's Law of Retail Gravitation and the maximum entropy method, since most points of interests provide services for surrounding communities, reflecting the vitality in a bottom-up way. The results indicate that the natural city defined by points of interests shows a high resolution and accuracy, providing a method to define the natural city with POIs.
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Despite being crucial for energy generation in most forms of life, few if any microbial antibiotics specifically inhibit glycolysis. To develop a specific inhibitor of the glycolytic enzyme enolase 2 (ENO2) for the treatment of cancers with deletion of ENO1 (encoding enolase 1), we modeled the synthetic tool compound inhibitor phosphonoacetohydroxamate (PhAH) into the active site of human ENO2. A ring-stabilized analog of PhAH, in which the hydroxamic nitrogen is linked to Cα by an ethylene bridge, was predicted to increase binding affinity by stabilizing the inhibitor in a bound conformation. Unexpectedly, a structure-based search revealed that our hypothesized backbone-stabilized PhAH bears strong similarity to SF2312, a phosphonate antibiotic of unknown mode of action produced by the actinomycete Micromonospora, which is active under anaerobic conditions. Here, we present multiple lines of evidence, including a novel X-ray structure, that SF2312 is a highly potent, low-nanomolar inhibitor of enolase.
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Inibidores Enzimáticos/farmacologia , Organofosfonatos/farmacologia , Fosfopiruvato Hidratase/antagonistas & inibidores , Pirrolidinonas/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estrutura Molecular , Organofosfonatos/química , Fosfopiruvato Hidratase/metabolismo , Pirrolidinonas/química , Relação Estrutura-AtividadeRESUMO
Imatinib mesylate (Gleevec) inhibits Abl1, c-Kit, and related protein tyrosine kinases (PTKs) and serves as a therapeutic for chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib also has efficacy against various pathogens, including pathogenic mycobacteria, where it decreases bacterial load in mice, albeit at doses below those used for treating cancer. We report that imatinib at such low doses unexpectedly induces differentiation of hematopoietic stem cells and progenitors in the bone marrow, augments myelopoiesis but not lymphopoiesis, and increases numbers of myeloid cells in blood and spleen. Whereas progenitor differentiation relies on partial inhibition of c-Kit by imatinib, lineage commitment depends upon inhibition of other PTKs. Thus, imatinib mimics "emergency hematopoiesis," a physiological innate immune response to infection. Increasing neutrophil numbers by adoptive transfer sufficed to reduce mycobacterial load, and imatinib reduced bacterial load of Franciscella spp., which do not utilize imatinib-sensitive PTKs for pathogenesis. Thus, potentiation of the immune response by imatinib at low doses may facilitate clearance of diverse microbial pathogens.
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Diferenciação Celular/efeitos dos fármacos , Francisella/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Mesilato de Imatinib/farmacologia , Mielopoese/efeitos dos fármacos , Neutrófilos/imunologia , Animais , Diferenciação Celular/imunologia , Contagem de Leucócitos , Camundongos , Mielopoese/imunologiaRESUMO
An HPMA-based polymeric prodrug of a CXCR4 antagonist, AMD3465 (P-SS-AMD), was developed as a dual-function carrier of therapeutic miRNA. P-SS-AMD was synthesized by a copolymerization of HPMA with a methacrylamide monomer in which the AMD3465 was attached via a self-immolative disulfide linker. P-SS-AMD showed effective release of the parent AMD3465 drug following treatment with intracellular levels of glutathione (GSH). The AMD3465 was released in the cells and exhibited functional CXCR4 antagonism, demonstrated by inhibition of the CXCR4-mediated cancer cell invasion. Due to its cationic character, P-SS-AMD could form polyplexes with miRNA and mediate efficient transfection of miR-200c mimics to downregulate expression of a downstream target ZEB-1 in cancer cells. The combined P-SS-AMD/miR-200c polyplexes showed improved ability to inhibit cancer cell migration when compared with individual treatments. The reported findings validate P-SS-AMD as a dual-function delivery vector that can simultaneously deliver a therapeutic miRNA and function as a polymeric prodrug of CXCR4 antagonist.
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Metacrilatos/química , MicroRNAs/química , Pró-Fármacos/química , Piridinas/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , MicroRNAs/genética , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/metabolismoRESUMO
To enhance the accumulation and penetration of nanomedicines in tumor tissue, we developed and evaluated the biological properties of matrix metalloproteinase 2 (MMP-2)-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer drugs and tumor-penetrating peptide conjugates (P-DOX-PLGLAG-iRGD). Two different spacers were used in the design: a lysosomally (cathepsin B) cleavable tetrapeptide GFLG spacer conjugated doxorubicin (DOX) to HPMA copolymer, and an MMP-2-degradable linker (PLGLAG) connected tumor-homing and -penetrating cyclic peptide iRGD to HPMA copolymer. The accumulation of DOX in P-DOX-PLGLAG-iRGD-treated monolayer (2D) and multilayer (3D) DU-145 prostate cancer cells was higher than that of control groups (P-DOX and P-DOX + iRGD). The cell cycle arrest analysis and cytotoxicity data demonstrated that P-DOX-PLGLAG-iRGD produced a higher G2/M arrest and possessed stronger cytotoxicity against DU-145 cells than P-DOX + iRGD or P-DOX, which was consistent with the drug uptake results. Similarly, P-DOX-PLGLAG-iRGD demonstrated the highest penetration ability in 3D multicellular DU-145 tumor cell spheroids. The results indicate that covalent conjugation of iRGD via MMP-2-sensitive bonds enhances accumulation and penetration of nanomedicines into tumor cell monolayers and spheroids.
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Acrilamidas/química , Antibióticos Antineoplásicos/metabolismo , Doxorrubicina/metabolismo , Portadores de Fármacos/química , Metaloproteinase 2 da Matriz/metabolismo , Oligopeptídeos/química , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Metaloproteinase 2 da Matriz/química , Estrutura Molecular , Oligopeptídeos/metabolismo , Polímeros/química , Relação Estrutura-AtividadeRESUMO
In this Letter, we present a concise strategy to prepare a conjugate of the tumor homing peptide iRGD and histone deacetylase inhibitor valproic acid, VPA-GFLG-iRGD. The conjugate VPA-GFLG-iRGD and a mixture of VPA and GFLG-iRGD have shown similar cytotoxicity against DU-145 prostate cancer cells. However, the treatment of DU-145 cells with conjugate VPA-GFLG-iRGD resulted in a decreased percentage of cells in the G2 phase, whereas the exposure of a mixture of VPA and GFLG-iRGD led to an increased percentage of cells in the G2 phase. We also found that GFLG-iRGD possessed cytotoxicity at the tested concentrations.
Assuntos
Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/farmacologia , Oligopeptídeos/síntese química , Oligopeptídeos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Ácido Valproico/química , Ácido Valproico/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Inibidores de Histona Desacetilases/química , Humanos , Masculino , Estrutura Molecular , Oligopeptídeos/química , Ácido Valproico/síntese químicaRESUMO
We synthesized two series of imatinib mesylate (STI-571) analogs to develop a Bcr-Abl and c-KIT receptor-specific labeling agent for positron emission tomography (PET) imaging to measure Bcr-Abl and c-KIT expression levels in a mouse model. The methods of molecular modeling, synthesis of STI-571 and its analogs, in vitro kinase assays, and radiolabeling are described. Molecular modeling revealed that these analogs bind the same Bcr-Abl and c-KIT binding sites as those bound by STI-571. The analogs potently inhibit the tyrosine kinase activity of Bcr-Abl and c-KIT, similarly to STI-571. [(18)F]-labeled STI-571 was prepared with high specific activity (75 GBq/µmol) by nucleophilic displacement and an average radiochemical yield of 12%. [(131)I]-labeled STI-571 was prepared with high purity (>95%) and an average radiochemical yield of 23%. The uptake rates of [(18)F]-STI-571 in K562 cells expressing Abl and in U87WT cells overexpressing c-KIT were significantly higher than those in the U87 cell and could be inhibited by STI-71 (confirming the specificity of uptake). PET scans of K562 and U87WT tumor-bearing mice with [(18)F]-STI-571 as a contrast agent showed visible tumor uptake and tumor-to-non-target contrast.
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Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Proteínas de Fusão bcr-abl/metabolismo , Piperazinas/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Pirimidinas/uso terapêutico , Animais , Antineoplásicos/química , Benzamidas/química , Modelos Animais de Doenças , Humanos , Mesilato de Imatinib , Camundongos , Modelos Moleculares , Piperazinas/química , Pirimidinas/químicaRESUMO
A series of degrasyn-like symmetrical compounds have been designed, synthesized, and screened against B cell malignancy (multiple myeloma, mantle cell lymphoma) cell lines. The lead compounds T5165804 and CP2005 showed higher nanomolar potency against these tumor cells in comparison to degrasyn and inhibited Usp9x activity in vitro and in intact cells. These observations suggest that this new class of compounds holds promise as cancer therapeutic agents.
Assuntos
Antineoplásicos/química , Nitrilas/química , Piridinas/química , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cianoacrilatos , Dimerização , Humanos , Modelos Moleculares , Mieloma Múltiplo/tratamento farmacológico , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Ubiquitina Tiolesterase/antagonistas & inibidores , Ubiquitina Tiolesterase/metabolismoRESUMO
A virtual library of 54 inositol analog mimics of In(1,4,5)P3 has been docked, scored, and ranked within the binding site of human inositol 1,4,5-trisphosphate 3-kinase A (IP3-3KA). Chemical synthesis of the best scoring structure that also met distance criteria for 3'-OH to -P in Phosphate has been attempted along with the synthesis of (1S,2R,3S,4S)-3-fluoro-2,4-dihydroxycyclohexanecarboxylic acid as an inositol analog, useful for non-invasive visualization and quantitation of IP3-3KA enzymatic activity.
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Curcumin (diferuloylmethane) is a potent anti-inflammatory and anti-tumorigenic agent that has shown preclinical activity in diverse cancers. Curcumin up-regulates heat shock protein 70 (hsp70) mRNA in several different cancer cell lines. Hsp70 contributes to an escape from the apoptotic effects of curcumin by several different mechanisms including prevention of the release of apoptosis inducing factor from the mitochondria and inhibition of caspases 3 and 9. Previously we showed that the combination of curcumin plus a heat shock protein inhibitor was synergistic in its down-regulation of the proliferation of a human schwannoma cell line (HEI-193) harboring an NF2 mutation, possibly because curcumin up-regulated hsp70, which also binds merlin, the NF2 gene product. In order to determine if curcumin also interacts directly with hsp70 and to discover other binding partners of curcumin, we synthesized biotinylated curcumin (bio-curcumin) and treated HEI-193 schwannoma cells. Cell lysates were prepared and incubated with avidin-coated beads. Peptides pulled down from this reaction were sequenced and it was determined that biotinylated curcumin bound hsp70, hsp90, 3-phosphoglycerate dehydrogenase, and a ß-actin variant. These binding partners may serve to further elucidate the underlying mechanisms of curcumin's actions.
Assuntos
Curcumina/química , Proteínas de Choque Térmico HSP70/química , Proteínas de Choque Térmico HSP90/química , Fosfoglicerato Desidrogenase/química , Sítios de Ligação , Biotina/química , Linhagem Celular Tumoral , Curcumina/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Simulação de Acoplamento Molecular , Neurilemoma/metabolismo , Neurilemoma/patologia , Fosfoglicerato Desidrogenase/metabolismo , Ligação Proteica , Estrutura Terciária de ProteínaRESUMO
An improved method for the synthesis of 17ß-hydroxy-16α-iodo-wortmannin along with the first synthesis of 17ß-hydroxy-16α-iodoPX866 and [(131)I] radiolabeled 17ß-hydroxy-16α-[(131)I]iodo-wortmannin, as potential PET tracers for PI3K was also described. The differences between wortmannin and its iodo analogue were compared by covalently docking each structure to L833 in PI3K.
Assuntos
Androstadienos/química , Androstadienos/síntese química , Gonanos/síntese química , Compostos Radiofarmacêuticos/síntese química , Sítios de Ligação , Gonanos/química , Radioisótopos do Iodo/química , Marcação por Isótopo , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinase/química , Fosfatidilinositol 3-Quinase/metabolismo , Tomografia por Emissão de Pósitrons , Estrutura Terciária de Proteína , Compostos Radiofarmacêuticos/química , WortmaninaRESUMO
The C1-C6 region of the potent cytotoxic agent psymberin has been synthesized. The key transformations of the synthesis are an auxiliary-controlled addition of a Sn(II)-glycolate enolate to an aldehyde to yield the anti aldol product and transforming the primary alcohol into a terminal olefin utilizing organoselenium chemistry.
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We report the synthesis of a macrocycle utilizing a novel framework of standard amino acids in combination with subunits that we have named as Linked Amino Acid Mimetics (LAAM's). Macrocycles based on the LAAM concept provide both a peptide targeting region and two independently variable functional regions. In the prototype structure, the commonly known Arg-Gly-Asp (RGD) sequence was used for the targeting region. The functional regions contain a phenyl group, and the linkage was formed via a Ring-Closing Metathesis (RCM) reaction.
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Cerebral cavernous malformation (CCM) is a type of vascular anomaly that arises due to the dyshomeostasis of brain capillary networks. In the past two decades, many advances have been made in this research field. Notably, as a more reasonable current view, the CCM lesions should be attributed to the results of a great number of additional events related to the homeostasis disorder of the endothelial cell. Indeed, one of the most fascinating concerns in the research field is the inflammatory perturbation in the immune microenvironment, which would affect the disease progression as well as the patients' outcomes. In this work, we focused on this topic, and underlined the immune-related factors' contribution to the CCM pathologic progression.
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Hemangioma Cavernoso do Sistema Nervoso Central , Encéfalo/patologia , Células Endoteliais/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/etiologia , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Humanos , Microambiente TumoralRESUMO
The outbreak of the COVID-19 has become a worldwide public health challenge for contemporary cities during the background of globalization and planetary urbanization. However, spatial factors affecting the transmission of the disease in urban spaces remain unclear. Based on geotagged COVID-19 cases from social media data in the early stage of the pandemic, this study explored the correlation between different infectious outcomes of COVID-19 transmission and various factors of the urban environment in the main urban area of Wuhan, utilizing the multiple regression model. The result shows that most spatial factors were strongly correlated to case aggregation areas of COVID-19 in terms of population density, human mobility and environmental quality, which provides urban planners and administrators valuable insights for building healthy and safe cities in an uncertain future.
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COVID-19 , Mídias Sociais , COVID-19/epidemiologia , China/epidemiologia , Cidades/epidemiologia , Humanos , Pandemias , SARS-CoV-2RESUMO
In recent years, with the current access in techniques, studies have significantly advanced the knowledge on meningeal immunity, revealing that the central nervous system (CNS) border acts as an immune landscape. The latest concept of meningeal immune system is a tertiary structure, which is a comprehensive overview of the meningeal immune system from macro to micro. We comprehensively reviewed recent advances in meningeal immunity, particularly the new understanding of the dural sinus and meningeal lymphatics. Moreover, based on the clues from the meningeal immunity, new insights were proposed into the dural arteriovenous fistula (DAVF) pathology, aiming to provide novel ideas for DAVF understanding.
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Malformações Vasculares do Sistema Nervoso Central , Humanos , Sistema Imunitário/fisiologiaRESUMO
Urban blue-green space (UBGS), as an important component of the urban environment, is found to closely relate to human health. An extensive understanding of the effects of UBGS on human health is necessary for urban planning and intervention schemes towards healthy city development. However, a comprehensive review and discussion of relevant studies using bibliometric methods is still lacking. This paper adopted the bibliometric method and knowledge graph visualization technology to analyze the research on the impact of UBGS on residents' health, including the number of published papers, international influence, and network characteristics of keyword hotspots. The key findings include: (1) The number of articles published between 2001 and 2021 shows an increasing trend. Among the articles collected from WoS and CNKI, 38.74% and 32.65% of the articles focus on physical health, 38.32% and 30.61% on mental health, and 17.06% and 30.61% on public health, respectively. (2) From the analysis of international partnerships, countries with high levels of economic development and urbanization have closer cooperation than other countries. (3) UBGS has proven positive effects on residents' physical, mental, and public health. However, the mediating effects of UBGS on health and the differences in the health effects of UBGS on different ages and social classes are less studied. Therefore, this study proposes several future research directions. First, the mediating effect of UBGS on health impacts should be further examined. Furthermore, the interactive effects of residents' behaviors and the UBGS environment should be emphasized. Moreover, multidisciplinary integration should be strengthened. The coupling mechanism between human behavior and the environment should also be studied in depth with the help of social perception big data, wearable devices, and human-computer interactive simulation. Finally, this study calls for developing health risk monitoring and early warning systems, and integrating health impact assessment into urban planning, so as to improve residents' health and urban sustainability.