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1.
Knee ; 33: 365-373, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34753026

RESUMO

BACKGROUND: The relationship between preoperative tibiofemoral position and failure of anterior cruciate ligament (ACL) reconstruction has been widely discussed. Most established methods for measuring tibiofemoral position on magnetic resonance imaging (MRI) mainly focus on anterior tibial subluxation (ATS), while a quantitative measuring method for rotational tibial subluxation (RTS) is still undetermined. Moreover, there are still controversies about the related factors for ATS. The aim of this study was to quantitatively describe preoperative ATS and RTS in ACL-injured and ACL-intact knees and identify the related factors for ATS and RTS based on MRI images. METHODS: Demographic data and preoperative MRIs of 104 ACL-injured patients were retrospectively analyzed. ACL-intact knees were 1:1 matched as control group. ATS was measured using longitudinal tibial axis, and RTS was determined by the difference between lateral and medial ATS. Related factors for ATS and RTS were examined. RESULTS: Increased lateral ATS (P < 0.0001), medial ATS (P < 0.0001) and RTS (P = 0.0479) were observed in ACL-injured knees compared with the control group. Increased posterior tibial slope (PTS), Beighton Score ≥ 4, presence of meniscal injury and long injury-to-MRI time were identified as being correlated with the increase of ATS. Factors for the increase of RTS were increased lateral PTS, Beighton score ≥ 4, presence of lateral meniscal injury, and left side. CONCLUSIONS: In ACL-injured knees, tibia not only subluxated anteriorly in both lateral and medial compartments, but also rotated internally. During preoperative planning, attentions should be paid to the factors that are correlated with altered tibiofemoral position.

2.
Nanoscale ; 13(45): 19085-19097, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34761764

RESUMO

Polypyrrole (PPy) nanoparticles have been widely studied in tumor photothermal therapy (PTT) for their significant photostability, good biocompatibility, and excellent photothermal performance. Herein, we report bovine serum albumin (BSA) stabilized PPy that were mineralized by MnO2 nanozyme on the surface (PPy@BSA-MnO2) to achieve synergistic photothermal and chemodynamic therapy (CDT) for breast cancer. In this multifunctional nanoplatform, the surface-loaded MnO2 undergoes a redox reaction with glutathione (GSH) to generate glutathione disulfide (GSSG) and Mn2+. Then, Mn2+ can convert H2O2 into a highly cytotoxic ˙OH to achieve chemodynamic therapy (CDT) and possess good magnetic resonance (MR) T1-weighted imaging capabilities to realize contrast imaging of the 4T1 tumor-bearing mouse models. In addition, PPy nanoparticles can efficiently convert near-infrared light energy into heat and achieve PTT. Most importantly, PPy@BSA-MnO2 nanoprobes have excellent in vitro 4T1 cell-killing effect and in vivo tumor-suppressive properties. The acute toxicity assessment results indicate that PPy@BSA-MnO2 nanoprobes have good biological safety. Therefore, the as-prepared multifunctional PPy@BSA-MnO2 nanoprobes possess excellent performance to promote MRI-guided PTT/CDT synergistic therapy for breast cancer treatment and have extensive clinical transformation and application prospects.


Assuntos
Neoplasias , Polímeros , Animais , Peróxido de Hidrogênio , Imageamento por Ressonância Magnética , Compostos de Manganês , Camundongos , Óxidos , Pirróis , Nanomedicina Teranóstica
3.
Microsyst Nanoeng ; 7: 55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567768

RESUMO

Assessment of lung and heart states is of critical importance for patients with pneumonia. In this study, we present a small-sized and ultrasensitive accelerometer for continuous monitoring of lung and heart sounds to evaluate the lung and heart states of patients. Based on two-stage amplification, which consists of an asymmetric gapped cantilever and a charge amplifier, our accelerometer exhibited an extremely high ratio of sensitivity to noise compared with conventional structures. Our sensor achieves a high sensitivity of 9.2 V/g at frequencies less than 1000 Hz, making it suitable to use to monitor weak physiological signals, including heart and lung sounds. For the first time, lung injury, heart injury, and both lung and heart injuries in discharged pneumonia patients were revealed by our sensor device. Our sound sensor also successfully tracked the recovery course of the discharged pneumonia patients. Over time, the lung and heart states of the patients gradually improved after discharge. Our observations were in good agreement with clinical reports. Compared with conventional medical instruments, our sensor device provides rapid and highly sensitive detection of lung and heart sounds, which greatly helps in the evaluation of lung and heart states of pneumonia patients. This sensor provides a cost-effective alternative approach to the diagnosis and prognosis of pneumonia and has the potential for clinical and home-use health monitoring.

4.
Horm Metab Res ; 53(9): 625-632, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34496413

RESUMO

MicroRNA-519d-3p (miR-519d-3p) has emerged as a tumor suppressor in several human cancers. But whether miR-519d-3p is involved in papillary thyroid cancer (PTC) remains elusive. In this study, we investigated the potential relevance of miR-miR-519d-3p in PTC. A retrospective study of 119 PTCs was carried out. The RT-qPCR analysis was used to measure the expression of miR-519d-3p and FOXQ1 in PTC tissues and cells. Chi-square test, Kaplan-Meier curve analysis, and multivariate Cox regression analyses were performed to assess the clinical and prognostic value of miR-519d-3p in PTC. Then cellular experiments were used to explore its biological effects on PTC cells. Finally, the Pearson correlation coefficient, dual-luciferase reporter assay, and rescue experiments were used to analyze the association between miR-519d-3p and FOXQ1. miR-519d-3p was significantly downregulated in PTC tissues and cell lines. The decreased expression of miR-519d-3p was associated with reduced overall survival and progression-free survival of patients. The proliferative, migratory, and invasive abilities of cells were blocked or elevated after upregulation or downregulation of miR-519d-3p, while FOXQ1 reversed these cellular behaviors caused after upregulation or knockdown of miR-519d-3p. In conclusion, miR-519d-3p was downregulated in PTC and associated with OS and PFS of patients. MiR-519d-3p may be a tumor-inhibiting miRNA in PTC, and that miR-519d-3p/FOXQ1 axis mediated PTC tumor progression from cell proliferation, migration, and invasion in PTC cells.

5.
ISME J ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34552194

RESUMO

Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventive therapy, but the transfer of pathogenic microbes or toxic compounds raise concern. Removal of bacteria from donor feces by micropore filtering may reduce this risk of bacterial infection, while residual bacteriophages could maintain the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of fecal filtrate transplantation (FFT). Using fecal material from healthy suckling piglets, we compared rectal FMT administration (FMT, n = 16) with cognate FFT by either rectal (FFTr, n = 14) or oro-gastric administration (FFTo, n = 13) and saline (CON, n = 16) in preterm, cesarean-delivered piglets as models for preterm infants. We assessed gut pathology and analyzed mucosal and luminal bacterial and viral composition using 16S rRNA gene amplicon and meta-virome sequencing. Finally, we used isolated ileal mucosa, coupled with RNA-Seq, to gauge the host response to the different treatments. Oro-gastric FFT completely prevented NEC, which was confirmed by microscopy, whereas FMT did not perform better than control. Oro-gastric FFT increased viral diversity and reduced Proteobacteria relative abundance in the ileal mucosa relative to control. An induction of mucosal immunity was observed in response to FMT but not FFT. As preterm infants are extremely vulnerable to infections, rational NEC-preventive strategies need incontestable safety profiles. We show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects.

6.
BMJ Open ; 11(7): e043416, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226211

RESUMO

OBJECTIVE: This study aimed to explore the association between famine exposure in early life and the odds of rheumatoid arthritis (RA) in adulthood. DESIGN: A population-based retrospective cohort study. SETTING: China. PARTICIPANTS: A total of 111 706 participants (1775 with RA) born from 1956 to 1964 were selected from the baseline survey of a large cohort in China. PRIMARY AND SECONDARY OUTCOME MEASURES: Four famine exposure groups were generated based on dates of birth, namely prenatal-exposed, infant-exposed, preschool-exposed and non-exposed groups. Logistic regressions were used to explore the association between famine exposure and self-reported RA in adulthood, adjusting for sex, region, monthly income, highest education, alcohol consumption, tobacco use, body mass index (BMI) and metabolic equivalent tasks. Analyses were also performed with stratification for sex (female or male), residing region (urban or rural), famine severity (severe or non-severe) and BMI (≥24 or <24). RESULTS: The study included 1775 (1.59%) RA cases and 109 931 (98.41%) non-RA controls. Among them, 22 413 (20.06%) were prenatal-exposed, 14 899 (13.34%) were infant-exposed and 34 356 (30.76%) were preschool-exposed. Prenatal exposure to famine was not associated with onset of RA in adulthood. Infant-exposed group and preschool-exposed group had significantly elevated odds of getting RA compared with non-exposed group (infant-exposed: OR=1.44, 95% CI 1.24 to 1.67; preschool-exposed: OR=1.38, 95% CI 1.22 to 1.57, p<0.001), and the relationship was stronger among women, urban residents and participants with BMI ≥24. Similar results were additionally observed when an age-balanced control group was used. CONCLUSIONS: Exposure to the Great Chinese Famine in early life after birth especially in infancy may be associated with a higher risk of RA in adulthood. Strengthening early-life nutrition could be an implication to prevent future RA.


Assuntos
Artrite Reumatoide , Efeitos Tardios da Exposição Pré-Natal , Adulto , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/etiologia , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Fome Epidêmica , Feminino , Humanos , Lactente , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Prevalência , Estudos Retrospectivos
7.
Pediatr Res ; 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112973

RESUMO

BACKGROUND: Necrotizing enterocolitis (NEC), a severe gut disorder in preterm infants, is difficult to predict due to poor specificity and sensitivity of clinical signs and biomarkers. Using preterm piglets as a model, we hypothesized that early development of NEC affects blood gene expression, potentially related to early systemic immune responses. METHODS: A retrospective analysis of clinical, tissue, and blood data was performed on 129 formula-fed piglets with NEC diagnosis at necropsy on day 5. Subgroups of NEC (n = 20) and control piglets (CON, n = 19) were analyzed for whole-blood transcriptome. RESULTS: Preterm piglets had variable NEC lesions, especially in the colon region, without severe clinical signs (e.g. normal growth, activity, hematology, digestion, few piglets with bloody stools). Transcriptome analysis showed 344 differentially expressed genes (DEGs) between NEC and CON piglets. Validation experiment showed that AOAH, ARG2, FKBP5, PAK2, and STAT3 were among the genes affected by severe lesions on day 5, when analyzed in whole blood and in dried blood spots (DBS). CONCLUSION: Whole-blood gene expressions may be affected in preterm pigs before clinical signs of NEC get severe. Blood gene expression analysis, potentially using DBS samples, is a novel tool to help identify new early biomarkers of NEC. IMPACT: Preterm pig model was used to investigate if blood transcriptomics could be used to identify new early blood biomarkers of NEC progression. Whole-blood transcriptome revealed upregulation of target genes in NEC cases when clinical symptoms are subtle, and mainly colon regions were affected. Differential NEC-associated gene expressions could be detected also in dried blood spots, potentially allowing easy collection of small blood volumes in infants.

8.
Behav Brain Res ; 411: 113374, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34023306

RESUMO

Major depressive disorder (MDD) is a severe mental disorder, which is closely related to the deficiency of monoamine neurotransmitters. Our previous study suggested that acute treatment with J147, a novel curcumin derivative, produced antidepressant-like effects in mouse model of depression by regulation of 5-HT receptor subtypes. However, it is still unknown whether the antidepressant-like effects of J147 are involved in activation of central monoaminergic system. In this study, a series of classical behavior tests were employed to assess the involvement of monoaminergic system in antidepressant- and anxiolytic-like effects after sub-acute treatment of mice with J147 for 3 days. The results suggested that J147 at 10 mg/kg significantly reduced the immobility time in both the tail suspension and forced swimming tests, but didn't show effects in the sucrose preference test. Similarly, sub-acute treatment of J147 did not induce amelioration in novelty suppressed feeding test. J147 increased duration and crossing time in the central area, but did not show significant change in rearing counts in the open field test. In neurochemical assays, studies suggested that serotonin and noradrenaline levels were significantly increased in the frontal cortex and hippocampus after treatment of J147 by the high-performance liquid chromatography (HPLC) with an electrochemical detector. Moreover, J147-induced significant inhibition of monoamine oxidase A activity. These findings suggest that the antidepressant- and anxiolytic-like effects of J147 might be related to the monoaminergic system by the evidence that high dose of J147 inhibits monoamine oxidase (MAO)-A activity and increases synaptic monoamines in the mouse brain.

9.
Am J Physiol Gastrointest Liver Physiol ; 321(1): G18-G28, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34009048

RESUMO

Preterm infants are at high risks of sepsis and necrotizing enterocolitis (NEC). Some develop sepsis shortly after suspected or confirmed NEC, implying that NEC may predispose to sepsis but the underlying mechanisms are unknown. Using NEC-sensitive preterm pigs as models, we investigated the immune status in animals following development of subclinical NEC-like lesions with variable severities. Caesarean-delivered preterm pigs were reared until day 5 or day 9. Blood was analyzed for T-cell subsets, neutrophil phagocytosis, transcriptomics, and immune responses to in vitro LPS challenge. Gut tissues were used for histology and cytokine analyses. Pigs with/without macroscopic NEC lesions were scored as healthy, mild, or severe NEC. Overall NEC incidence was similar on day 5 and day 9 (61%-62%) but with lower severity on day 9, implying gradual mucosal repair following the early phase of NEC. Pigs with NEC showed decreased goblet cell density and increased MPO+ and CD3+ cell infiltration in the distal small intestine or colon. Mild or severe NEC lesions had limited effects on circulating parameters on day 5. On day 9, pigs with NEC lesions (especially severe lesions) showed systemic immune suppression, as indicated by elevated Treg frequency, impaired neutrophil phagocytosis, low expression of genes related to innate immunity and Th1 polarization, and diminished LPS-induced immune responses. In conclusion, we shows evidence for NEC-induced systemic immune suppression, even with mild and subclinical NEC lesions. The results help to explain that preterm infants suffering from NEC may show high sensitivity to later secondary infections and sepsis.NEW & NOTEWORTHY Necrotizing enterocolitis (NEC) and sepsis are common diseases in preterm infants. Many develop sepsis following an episode of suspected NEC, suggesting NEC as a predisposing factor for sepsis but mechanisms are unclear. Using preterm pigs as a model, now we show that subclinical NEC lesions, independent of clinical confounding factors, induces systemic immune suppression. The results may help to explain the increased risks of infection and sepsis in preterm infants with previous NEC diagnosis.


Assuntos
Citocinas/metabolismo , Enterocolite Necrosante/metabolismo , Neutrófilos/imunologia , Sepse/imunologia , Animais , Animais Recém-Nascidos , Feminino , Neutrófilos/metabolismo , Gravidez , Nascimento Prematuro , Risco , Sepse/complicações , Suínos
10.
J Pediatr Gastroenterol Nutr ; 73(2): e39-e46, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33853107

RESUMO

OBJECTIVES: Exclusive feeding with bovine colostrum (BC) protects preterm pigs against necrotizing enterocolitis (NEC) and BC has recently been tested as a supplement to a mother's own milk or formula (FOR) for very preterm infants. Using preterm pigs as a model for infants, we investigated if BC has gut- and NEC-protective effects at different proportions of the daily enteral intake given as BC. METHODS: Sixty-eight caesarean-delivered preterm piglets (90% gestation) were allocated into four groups with increasing proportions of eight daily bolus feedings as BC: BC00 (only FOR feeding), BC25 (25% BC), BC50 (50% BC), or BC75 (75% BC). On day 5, the gut was collected for biochemical analyses. RESULTS: Body growth was increased in BC50 and BC75 piglets (2-fold, P < 0.05 vs BC00). The incidence of mild NEC-like lesions was similar among groups (67-86%), but BC75 reduced severe NEC-like lesions (27% vs 79% in BC00, P < 0.05). BC50 and BC75 improved hexose absorption and mucosal structure and reduced gut permeability (P < 0.05 vs BC00), while enzyme activities (lactase, aminopeptidase N and A, dipeptidyl peptidase IV) were improved in all pigs fed BC (P < 0.05). Across the measured variables, beneficial effects were most clear for the BC75 group, including reductions in colon tissue cytokine levels (interleukin 8, interleukin 1ß, tumor necrosis factor α) and expression of immune- and apoptosis-related genes (LBP, TLR4, TLR2, IL8, STAT3, IL17, C3, all P < 0.05, relative to BC00). CONCLUSION: A proportion of 50-75% of daily enteral intake as BC is required to improve the intestinal structure, function, immunology, and NEC resistance in preterm piglets also fed formula. Further studies are required to show if and how supplementary BC may support gut development in preterm infants during the immediate postnatal period. It is challenging to translate results on optimal feeding regimens between species, and preterm infants would not receive a majority of their daily enteral intake as BC.


Assuntos
Enterocolite Necrosante , Nascimento Prematuro , Animais , Animais Recém-Nascidos , Bovinos , Colostro , Enterocolite Necrosante/prevenção & controle , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Intestinos , Gravidez , Nascimento Prematuro/prevenção & controle , Suínos
11.
Sheng Li Xue Bao ; 73(1): 1-9, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33665654

RESUMO

Astrocytes are a heterogenous group of macroglia present in all regions of the brain and play critical roles in many aspects of brain development, function and disease. Previous studies suggest that the B-cell lymphoma-2 associated X protein (BAX)-dependent apoptosis plays essential roles in regulating neuronal number and achieving optimal excitation/inhibition ratio. The aim of the present paper was to study whether BAX regulates astrocyte distribution in a region-specific manner. Immunofluorescence staining of SOX9 was used to analyze and compare astrocyte density in primary somatosensory cortex, motor cortex, retrosplenial cortex and hippocampus in heterozygous and homozygous BAX knockout mice at age of six weeks when cortical development has finished and glia development has reached a relatively steady state. The results showed that astrocyte density varied significantly among different cortical subdivisions and between cortex and hippocampus. In contrast to the significant increase in GABAergic interneurons, the overall and region-specific astrocyte density remained unchanged in the cortex when BAX was absent. Interestingly, a significant reduction of astrocyte density was observed in the hippocampus of BAX knockout mice. These data suggest that BAX differentially regulates neurons and astrocytes in cortex as well as astrocytes in different brain regions during development. This study provided important information about the regional heterogeneity of astrocyte distribution and the potential contribution of BAX gene during development.


Assuntos
Astrócitos , Hipocampo , Animais , Interneurônios , Camundongos , Neurônios , Proteína X Associada a bcl-2/genética
12.
J Mater Chem B ; 9(11): 2641-2655, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33683276

RESUMO

In our previous study, zinc oxide nanoparticles (ZnO NPs) presented satisfying therapeutic effects with cancer cell selectivity in osteosarcoma cells and, thus, have been considered as a potential nanomedicine for human osteosarcoma treatment. However, the poorly investigated internalization process, including their endocytic pathway into tumor cells and intracellular fate, limits the clinical application. Here, we further clarified these aspects. First, ZnO NPs were rapidly internalized by osteosarcoma cells and accumulated in mitochondria, before being entrapped into lysosomes. Second, dynasore (a dynamin inhibitor) was demonstrated to be the most effective in blocking ZnO NP uptake and rescuing ZnO NP-induced osteosarcoma cell autophagic death and apoptosis. Third, we confirmed the key role of dynamin 2 in ZnO NP endocytosis and subsequent autophagic cell death in vitro and in vivo. Furthermore, we proved that VPS34 transferred from cell cytoplasm to cell membrane to interact with dynamin under ZnO NP treatment. Altogether, combined with our previous study, the current research further revealed that ZnO NPs entered human osteosarcoma cells through the VPS34/dynamin 2-dependent endocytic pathway, directly targeting and damaging the mitochondria before being entrapped into the lysosomes, thereby initiating mitophagy-Zn2+-reactive oxygen species-mitophagy axis mediated cell apoptosis.


Assuntos
Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Dinamina II/metabolismo , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Óxido de Zinco/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Humanos , Mitocôndrias/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Óxido de Zinco/química
13.
Int J Dev Neurosci ; 81(2): 191-199, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33421197

RESUMO

Polycystic kidney disease with Tuberous sclerosis is a disease caused by the deletions of the TSC2-PKD1 gene. The disease is rarely reported and the characterized manifestation is severe polycystic kidney growth. The diagnosis can be made by molecular analysis. We report the first case of PKDTS discovered in infancy in China with typical neurological and renal manifestations. The patient has infantile spasm, polycystic kidney, skin damage, hypertension, and hematuria after infection. After effective treatment of Rapamycin, the seizures were completely controlled. There was not been any renal function damage in the patient. At the same time, we review the related literature and further elaborate on the variety of clinical manifestations, treatment, and prognosis.


Assuntos
Deleção de Genes , Rim Policístico Autossômico Recessivo/genética , Espasmos Infantis/genética , Esclerose Tuberosa/genética , Humanos , Lactente , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Rim Policístico Autossômico Recessivo/diagnóstico por imagem , Espasmos Infantis/diagnóstico por imagem , Esclerose Tuberosa/diagnóstico por imagem , Ultrassonografia
14.
Antiviral Res ; 187: 105015, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33444702

RESUMO

The newly emerged severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) coronavirus initiated a pneumonia outbreak (COVID-19) that rapidly spread worldwide and quickly became a public health emergency of international concern; However to date, except Remdesivir, there are no clinically approved specific or effective medicines to prevent or treat COVID-19. Therefore, the development of novel treatments against coronavirus infections caused by the current SARS-CoV-2 virus, as well as other highly pathogenic human coronaviruses, represents an urgent unmet need. Stimulator of interferon genes (STING) plays a central role in host defense mechanisms against microbial infections. STING activation leads to the induction of both type I interferon and autophagy responses, which elicit strong inhibitory effect against the infections caused by a broad range of microbial pathogens. However, whether STING activation can impact infections from SARS-CoV-2 or other coronaviruses remains largely unknown. In this study, we investigated the anti-coronavirus activity triggered by STING activation. We discovered that dimeric amidobenzimidazole (diABZI), a synthetic small molecule STING receptor agonist, showed potent anti-coronavirus activity against both the common cold human coronavirus 229E (HCoV-229E) and SARS-CoV-2 in cell culture systems. In addition, we demonstrated that the antiviral activity of diABZI was dependent on the interferon pathway in HCoV-229E infected normal human fibroblast lung cells (MRC-5) and reconstituted primary human airway air-liquid interface (ALI) cultures. Furthermore, low-dose of diABZI treatment at 0.1 µM effectively reduced the SARS-CoV-2 viral load at the epithelial apical surface and prevented epithelial damage in the reconstituted primary human bronchial airway epithelial ALI system. Our findings have thus revealed the therapeutic potential of STING agonists, such as diABZI, as treatments for SARS-CoV-2 and other human coronavirus infections.


Assuntos
Antivirais/farmacologia , Benzimidazóis/farmacologia , COVID-19/tratamento farmacológico , Coronavirus Humano 229E/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Proteínas de Membrana/agonistas , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Antivirais/química , Autofagia/efeitos dos fármacos , Brônquios/virologia , COVID-19/virologia , Linhagem Celular , Infecções por Coronavirus/virologia , Células Epiteliais/virologia , Humanos , Interferon Tipo I/farmacologia , Pulmão/virologia , Replicação Viral
15.
J Mol Neurosci ; 71(2): 245-251, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32617873

RESUMO

Metachromatic leukodystrophy(MLD) is an autosomal recessive hereditary neurodegenerative lysosomal storage disorder caused by the mutations in arylsulfatase A gene (ARSA), which results in the deficiency of ARSA enzyme. The common clinical characteristics of MLD are abnormal gait, and then gradually appears ataxia, spastic quadriplegia, optic atrophy, cortical blindness, and dementia. We describe two patients in China who were diagnosed with MLD and find that the four ARSA gene mutations (c.1115G>A, c.302G>T, c.893 G> T, and c.302G>T) are associated with MLD, in which c.893 G>T and c.302G>T are novel mutations by gene sequence and clinical manifestations, to further understand the relationship between MLD and ARSA gene.


Assuntos
/genética , Cerebrosídeo Sulfatase/genética , Leucodistrofia Metacromática/genética , Mutação de Sentido Incorreto , Transplante de Medula Óssea , Pré-Escolar , Progressão da Doença , Éxons/genética , Feminino , Estudos de Associação Genética , Humanos , Leucodistrofia Metacromática/etnologia , Leucodistrofia Metacromática/terapia , Masculino
16.
ACS Appl Mater Interfaces ; 12(43): 48296-48309, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33054172

RESUMO

Although ZnO nanoparticles (NPs) can kill human osteosarcoma cells, the underlying upstream regulatory mechanisms remain unclear. Since hypoxia inducible factor-1α (HIF-1α) regulates the tumor microenvironment, here we explored the interplay between HIF-1α regulation and mitophagy in ZnO NP-induced osteosarcoma inhibition both in vivo and in vitro. We found that ZnO NPs upregulated HIF-1α protein levels when they killed four common human osteosarcoma cell lines. This finding was consistent with our observations that additional HIF-1α upregulation by a hypoxia inducer CoCl2 or under a 1% hypoxia environment enhanced NP-induced cell death, but concurrent HIF-1α suppression by a hypoxia inhibitor YC-1 or HIF-1α siRNA inhibited NP-induced cell death. We discovered an interplay between HIF-1α and the autophagy-Zn2+-reactive oxygen species (ROS)-autophagy cycle axis and revealed that NP-induced cancer cell killing followed a HIF-1α-BNIP3-LC3B-mediated mitophagy pathway. We confirmed that NP-upregulated HIF-1α protein expression was attributed to prolyl hydroxylase inhibition by both ROS and Zn2+. In addition, the in vivo assay confirmed the therapeutic effectiveness and safety of ZnO NPs on a nude mice osteosarcoma model. Collectively, our findings clarified the upstream regulatory mechanism of autophagy induced by the NPs and further demonstrated their antitumor ability in vivo. This work provides new targets and strategies for enhancing NP-based osteosarcoma treatment.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Óxido de Zinco/farmacologia , Antineoplásicos/química , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Indazóis/farmacologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Tamanho da Partícula , RNA Interferente Pequeno/farmacologia , Propriedades de Superfície , Células Tumorais Cultivadas , Microambiente Tumoral/efeitos dos fármacos , Óxido de Zinco/química
17.
Exp Ther Med ; 20(3): 2805-2811, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32765775

RESUMO

Isokinetic muscle strength test implemented by the Biodex system is a method used for evaluating muscle function that has been applied clinically in the field of sports and rehabilitation medicine. However, information on its application on Haglund's deformity remain insufficient. Therefore, the present study examined the effectiveness of the muscle strength test using the Biodex system in evaluating the recovery of athletic capacity in patients with Haglund's deformity following endoscopic surgery. In total, 34 patients treated by the authors from June 2012 to November 2018 at Peking University Third Hospital (Beijing, China) were included. To compare muscle strength before surgery, then 3 and 6 months after surgery, using the uninjured side as the control, the Biodex system test was conducted in parallel to the collection of the American Orthopaedic Foot and Ankle Score values and visual analog scale scores. The Biodex system test results showed that Haglund's deformity mainly hinders plantar flexion strength. Patients recovered daily living capacity within 3 months and athletic capacity within 6 months following surgery, which matched the AOFAS values, VAS scores and the self-assessments of the patients. These findings suggest that the Biodex system can dynamically reflect the degree of postoperative recovery in Haglund's deformity.

18.
Eur J Obstet Gynecol Reprod Biol ; 252: 479-482, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32758858

RESUMO

OBJECTIVE: The universal two-child policy was implemented in January 2016 in China. The objective of this study was to compare the influence of change in fertility policy on obstetric issues. STUDY DESIGN: 2016 was taken as the cut-off point, and a retrospective study was conducted on data of patients who delivered in the China-Japan Friendship Hospital from January 2014 to December 2018. Maternal characteristics, mode of delivery, and pregnancy outcomes were studied in detail. RESULTS: Total 8931 babies were delivered from 2014 to 2018. There was a marked increase in the birth rate after the two-child policy. The percentage of elderly pregnant women and rate of cesarean sections increased significantly in 2017 and 2018. The primary cesarean section rates in 2017 and 2018 were significantly lower than those in 2014, 2015, and 2016. Increased incidence of placenta previa and postpartum hemorrhage were observed; however, no significant differences were seen in the rates of hypertensive disorders, gestational diabetes mellitus, and neonatal asphyxia within these five years. CONCLUSION: The implementation of two-child policy has changed the mode of obstetrics and has presented great challenges. With hierarchical management of high-risk patients and control of the cesarean section rate, we can ensure the safety of pregnant women and newborns.


Assuntos
Cesárea , Políticas , Idoso , Criança , China/epidemiologia , Parto Obstétrico , Feminino , Humanos , Recém-Nascido , Japão/epidemiologia , Gravidez , Estudos Retrospectivos
19.
Med Hypotheses ; 143: 110130, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32759009

RESUMO

In order to preserve paravertebral muscles and posterior ligaments complex (PLC), this paper proposes a new lumbar laminoplasty surgery for lumbar spinal stenosis (LSS). According to the anatomy of back muscles insertions, building block osteotomy (BBO) which aimed to achieve precise osteotomy and reconstruction based on modular design theory was firstly put forward, and supposed to be achieved by an ultrasound bone scalpel (UBS). In details, lumbar spinous processes are longitudinally split, then supraspinous and interspinous ligaments are sharply cut off longitudinally. After converting to lumbar flexion, lamina osteotomy is innovatively finished by an UBS through interspinous space. After decompression, hollow screws are firstly suggested to be used on each side to fix lamina and spinous processes, and PLC is reconstructed by interrupted suture. Feasibility of this method is evaluated in details. Challenges, advantages and disadvantages are also discussed.


Assuntos
Músculos do Dorso , Laminoplastia , Estenose Espinal , Descompressão Cirúrgica , Humanos , Vértebras Lombares/cirurgia , Osteotomia , Estenose Espinal/cirurgia
20.
Cardiovasc Ther ; 2020: 1615826, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695227

RESUMO

Background: Stress cardiomyopathy (SCM) is a transient reversible left ventricular dysfunction that more often occurs in women. Symptoms of SCM patients are similar to those of acute coronary syndrome (ACS), but little is known about biomarkers. The goals of this study were to identify the potentially crucial genes and pathways associated with SCM. Methods: We analyzed microarray datasets GSE95368 derived from the Gene Expression Omnibus (GEO) database. Firstly, identify the differentially expressed genes (DEGs) between SCM patients in normal patients. Then, the DEGs were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed and Cytoscape was used to find the key genes. Results: In total, 25 DEGs were identified, including 10 upregulated genes and 15 downregulated genes. These DEGs were mainly enriched in ECM-receptor interaction, dilated cardiomyopathy (DCM), human papillomavirus infection, and focal adhesion, whereas in GO function classification, they were mainly enriched in the extracellular region, positive regulation of the multicellular organismal process, establishment of localization, and intracellular vesicle. Conclusion: Seven hub genes contained APOE, MFGE8, ALB, APOB, SAA1, A2M, and C3 identified as hub genes of SCM, which might be used as diagnostic biomarkers or molecular targets for the treatment of SCM.


Assuntos
Antígenos de Superfície/genética , Apolipoproteína B-100/genética , Apolipoproteínas E/genética , Complemento C3/genética , Proteínas do Leite/genética , Albumina Sérica Humana/genética , Proteína Amiloide A Sérica/genética , Cardiomiopatia de Takotsubo/genética , Transcriptoma , Função Ventricular Esquerda/genética , alfa-Macroglobulinas/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas , Transdução de Sinais , Cardiomiopatia de Takotsubo/fisiopatologia
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