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1.
J Affect Disord ; 320: 576-589, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36179776

RESUMO

OBJECTIVE: Little is known about the pathogenesis underlying cognitive impairment in major depressive disorder (MDD). We aimed to explore the mechanisms of cognitive impairments among patients with MDD by investigating the dynamics of overlapping brain sub-networks. METHODS: Forty unmedicated patients with MDD and 28 healthy controls (HC) were enrolled in this study. Cognitive function was measured using the Chinese versions of MATRICS Consensus Cognitive Battery (MCCB). All participants were scanned using a whole-head resting-state magnetoencephalography (MEG) machine. The dynamism of neural sub-networks was analyzed based on the detection of overlapping communities in five frequency bands of oscillatory brain signals. RESULTS: MDD demonstrated poorer cognitive performance in six domains compared to HC. The difference in community detection (functional integration mode) in MDD was frequency-dependent. MDD showed significantly decreased community dynamics in all frequency bands compared to HC. Specifically, differences in the visual network (VN) and default mode network (DMN) were detected in all frequency bands, differences in the cognitive control network (CCN) were detected in the alpha2 and beta frequency bands, and differences in the bilateral limbic network (BLN) were only detected in the beta frequency band. Moreover, community dynamics in the alpha2 frequency band were positively correlated with verbal learning and reasoning problem solving abilities in MDD. CONCLUSIONS: Our study found that decreasing in the dynamics of overlapping sub-networks may differ by frequency bands. The aberrant dynamics of overlapping neural sub-networks revealed by frequency-specific MEG signals may provide new information on the mechanism of cognitive impairments that result from MDD.


Assuntos
Disfunção Cognitiva , Transtorno Depressivo Maior , Humanos , Magnetoencefalografia , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia
2.
Food Res Int ; 162(Pt B): 112110, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461409

RESUMO

The effects of different phenolic compounds on the interfacial behaviour of casein were investigated, and the action mechanism was further explored. Tannic acid, epigallocatechin gallate, quercetin and quercitrin promoted the aggregation of casein and decreased its solubility. Although the emulsifying and foaming capabilities of casein showed slight decrease with the treatment of phenolic compounds, its emulsifying and foaming stabilities were both greatly improved. By using fluorescence and circular dichroism spectra, phenolic compounds exhibited the capability to bind and form complexes with casein. Meanwhile, the binding interaction by phenolic compounds increased the α-helix content in casein and decreased its random coil content, which indicated a transition of the spatial conformation of casein from disorder to order. By using molecular docking, hydrogen bonds, hydrophobic interactions and Van der Waals were found in the interactions between phenolic compounds and casein. According to the analysis of spectroscopy and simulation results, the structure characteristics of phenolic compounds, including molecular weight, number and position of hydroxyl groups, acylation and glycosylation, exhibited significant effects on their interactions with casein, so as to affect the interfacial behaviour of casein. All present results suggested that phenolic compounds had the potential to improve the properties of casein in food and chemical industries.

3.
Front Plant Sci ; 13: 1019012, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466250

RESUMO

In wheat, the leaf chlorophyll content in flag leaves is closely related to the degree of phosphorus stress. Identifying major genes/loci associated with chlorophyll content in flag leaves under different phosphorus conditions is critical for breeding wheat varieties resistant to low phosphorus (P). Under normal, medium, and low phosphorus conditions, the chlorophyll content of flag leaves was investigated by a double haploid (DH) population derived from a cross between two popular wheat varieties Jinmai 47 and Jinmai 84, at different grain filling stages. Chlorophyll content of the DH population and parents decreased gradually during the S1 to the S3 stages and rapidly at the S4 stage. At the S4 stage, the chlorophyll content of the DH population under low phosphorus conditions was significantly lower than under normal phosphate conditions. Using a wheat 15K single-nucleotide polymorphism (SNP) panel, a total of 157 QTLs were found to be associated with chlorophyll content in flag leaf and were identified under three phosphorus conditions. The phenotypic variation explained (PVE) ranged from 3.07 to 31.66%. Under three different phosphorus conditions, 36, 30, and 48 QTLs for chlorophyll content were identified, respectively. Six major QTLs Qchl.saw-2B.1, Qchl.saw-3B.1, Qchl.saw-4D.1, Qchl.saw-4D.2, Qchl.saw-5A.9 and Qchl.saw-6A.4 could be detected under multiple phosphorus conditions in which Qchl.saw-4D.1, Qchl.saw-4D.2, and Qchl.saw-6A.4 were revealed to be novel major QTLs. Moreover, the closely linked SNP markers of Qchl.saw-4D.1 and Qchl.saw-4D.2 were validated as KASP markers in a DH population sharing the common parent Jinmai 84, showed extreme significance (P <0.01) in more than three environments under different phosphorus conditions, which has the potential to be utilized in molecular marker-assisted breeding for low phosphorus tolerance in wheat.

4.
Adv Sci (Weinh) ; : e2205462, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36453571

RESUMO

Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post-translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro-environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl-vWA domain-carrying proteins including integrin ß3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll-like receptor (TLR) family member TLR4 or TLR2 activation. TLR-activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)-mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3-K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle-like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36408586

RESUMO

INTRODUCTION: Antibody-drug conjugates (ADCs) are a relatively new class of anti-cancer therapies approved for a number of malignancies, including breast cancer. Their unique structure, consisting of a monoclonal antibody connected via a linker to a toxic payload, combines characteristics of both targeted therapy and chemotherapy. AREAS COVERED: In this review, we discuss the unique molecular structure and pharmacologic principles of ADCs and present the clinical efficacy and relevant toxicities of ADCs both approved and in development. While HER2 is the most studied target with approved agents for both HER2-positive and HER2-low expressing tumors, novel targets in HER2-negative disease have expanded our therapeutic capabilities significantly. EXPERT OPINION: ADCs are a promising, novel drug class with significant efficacy in all breast cancer subtypes. They are generally safe and well-tolerated. However, further research is necessary to improve their therapeutic potential. The development of predictive biomarkers to identify patients with greatest benefit, improved understanding of drug resistance to advance combination therapies, and novel targets are needed to further the field.

6.
Nat Commun ; 13(1): 6859, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369178

RESUMO

Immunoglobulin A (IgA) mediates mucosal responses to food antigens and the intestinal microbiome and is involved in susceptibility to mucosal pathogens, celiac disease, inflammatory bowel disease, and IgA nephropathy. We performed a genome-wide association study of serum IgA levels in 41,263 individuals of diverse ancestries and identified 20 genome-wide significant loci, including 9 known and 11 novel loci. Co-localization analyses with expression QTLs prioritized candidate genes for 14 of 20 significant loci. Most loci encoded genes that produced immune defects and IgA abnormalities when genetically manipulated in mice. We also observed positive genetic correlations of serum IgA levels with IgA nephropathy, type 2 diabetes, and body mass index, and negative correlations with celiac disease, inflammatory bowel disease, and several infections. Mendelian randomization supported elevated serum IgA as a causal factor in IgA nephropathy. African ancestry was consistently associated with higher serum IgA levels and greater frequency of IgA-increasing alleles compared to other ancestries. Our findings provide novel insights into the genetic regulation of IgA levels and its potential role in human disease.


Assuntos
Doença Celíaca , Diabetes Mellitus Tipo 2 , Glomerulonefrite por IGA , Doenças Inflamatórias Intestinais , Humanos , Camundongos , Animais , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/complicações , Estudo de Associação Genômica Ampla , Doença Celíaca/genética , Predisposição Genética para Doença , Diabetes Mellitus Tipo 2/complicações , Imunoglobulina A/genética , Rim/metabolismo
7.
Front Neurosci ; 16: 996325, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408378

RESUMO

To investigate the reorganizations of gray matter volume (GMV) in each subregion of primary motor cortex (M1) after incomplete cervical cord injury (ICCI) and to explore the differences in functional connectivity (FC) between the M1 subregions and the whole brain, and further to disclose the potential value of each M1 subregion in motor function rehabilitation of ICCI patients. Eighteen ICCI patients and eighteen age- and gender- matched healthy controls (HCs) were recruited in this study. The 3D high-resolution T1-weighted structural images and resting-state functional magnetic resonance imaging (rs-fMRI) of all subjects were obtained using a 3.0 Tesla MRI system. Based on the Human Brainnetome Atlas, the structural and functional changes of M1 subregions (including A4hf, A6cdl, A4ul, A4t, A4tl, A6cvl) in ICCI patients were analyzed by voxel-based morphometry (VBM) and seed-based FC, respectively. Compared with HCs, no structural changes in the M1 subregions of ICCI patients was detected. However, when compared with HCs, ICCI patients exhibited decreased FC in visual related areas (lingual gyrus, fusiform gyrus) and sensorimotor related areas (primary sensorimotor cortex) when the seeds were located in bilateral A4hf, A4ul, and decreased FC in visual related areas (lingual gyrus, fusiform gyrus) and cognitive related areas (temporal pole) when the seed was located in the left A4t. Moreover, when the seeds were located in the bilateral A6cdl, decreased FC in visual related areas (lingual gyrus, fusiform gyrus, calcarine gyrus) was also observed. Our findings demonstrated that each of the M1 regions had diverse FC reorganizations, which may provide a theoretical basis for the selection of precise stimulation targets, such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tCDS), meanwhile, our results may reveal the possible mechanism of visual feedback and cognitive training to promote motor rehabilitation.

8.
BMC Gastroenterol ; 22(1): 456, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380273

RESUMO

BACKGROUND: Trans-hepatic arterial chemoembolization (TACE) is a treatment option for liver cancer patients. It can prolong patients' survival but can also cause symptom distress. Symptom distress (SDs) can directly impact quality of life (QOL) and may indirectly influence QOL by lessening hope. In this study, we wanted to explore the mediating effect of hope on the relationship between SDs and QOL among patients with liver cancer receiving TACE. METHODS: A cross-sectional study was conducted from December 20, 2017, to August 6, 2018, at a gastroenterology ward of a medical center. The participants were 92 liver cancer patients (69.6% male, mean age 67.8) who were admitted for TACE treatment. Information on SDs, hope, and QOL was collected by questionnaire on discharge day. Hayes' PROCESS model was used to test the mediating effect of hope on the relationship between SDs and QOL. RESULTS: The mean score and standard deviation (SD) of SDs, hope, and QOL were 32.08 (SD = 6.22), 27.09 (SD = 3.51), and 55.16 (SD = 17.33), respectively. SDs negatively impacts quality of life. The total effect of SDs on QOL was - 1.41 (95% confidence interval [CI]: - 1.96, - 0.86). The indirect effect via the mediation of hope was - 0.95 (95% CI: - 1.7, - 0.45). Hope partially mediated the effect of SDs on QOL. CONCLUSION: SDs after TACE is vital; it directly reduces a patient's overall QOL and can indirectly hinder it by reducing the patient's hope. In addition to symptom management, interventions that help patients maintain their hope are key to improving QOL among patients receiving TACE.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Masculino , Idoso , Feminino , Qualidade de Vida , Carcinoma Hepatocelular/terapia , Estudos Transversais , Neoplasias Hepáticas/terapia , Quimioembolização Terapêutica/efeitos adversos
9.
Microbiol Spectr ; : e0274922, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36416559

RESUMO

Our previous study identified that the Mycobacterium abscessus subsp. abscessus T28 sequevar does not fully represent inducible macrolide resistance. Thus, we initiated a correlation study between genotypes and phenotypes. In total, 75 isolates from patients with skin and soft tissue infections were enrolled in the study. These strains were tested against 11 antimycobacterial agents using Sensitire RAPMYCO plates and the CLSI-recommended broth microdilution method. In order to analyze erm(41) and partial hsp65, rpoB, secA1, and rrl genes, bacterial genomic DNA was extracted from bacteria. The MEGA X software was used for phylogenetic analyses. The most active agents against most M. abscessus species were amikacin and tigecycline. Clarithromycin was effective toward M. abscessus subsp. massiliense and nearly all M. abscessus subsp. abscessus C28 sequevars. Two varieties of M. abscessus subsp. abscessus T28 sequevars did not represent inducible macrolide resistance. Most M. abscessus species showed intermediate susceptibility to cefoxitin and imipenem. Six additional agents were less effective against M. abscessus species. Following phylogenetic analyses, two outliers of M. abscessus subsp. abscessus T28 sequevars seem to represent no inducible macrolide resistance. In addition, we discovered genetic mosaicism of hsp65, rpoB, and secA1 in M. abscessus species was common. T28 sequevars of M. abscessus subsp. abscessus do not fully represent inducible macrolide resistance. The outlier of erm(41) phylogeny of the M. abscessus subsp. abscessus T28 sequevar is possibly due to macrolide susceptibility. Evaluation of the antimicrobial susceptibility of M. abscessus species is a reliable tool for assisting physicians in selecting the most effective antimycobacterial agent(s). IMPORTANCE Macrolides are the mainstays of the antimycobacterial regimens against Mycobacterium abscessus species (formerly Mycobacterium abscessus complex). erm(41) confers inducible macrolide resistance for M. abscessus subsp. bolletii strains, and the majority of M. abscessus subsp. abscessus T28 sequevars. Furthermore, the acquired macrolide resistance of M. abscessus species is due to a point mutation in rrl. However, not all M. abscessus subsp. abscessus T28 sequevars have inducible macrolide resistance. Exploration of the mechanism of macrolide resistance requires an understanding of genetic diversity. The genetic mosaicism of the erm(41), rpoB, hsp65, and secA1 genes within three subspecies of M. abscessus species is not uncommon. The T28 sequevar of erm(41) confers inducible macrolide resistance to the genetic mosaic strain. The development of new anti-M. abscessus species infection overcoming inducible macrolide resistance and/or acquired macrolide resistance is a crucial issue.

10.
Artigo em Chinês | MEDLINE | ID: mdl-36347579

RESUMO

Objective:To explore the correlation between the parameters of video head impulse test (vHIT)and dizziness handicap inventory (DHI) score in patients with vestibular neuritis. Methods:Clinical data of 46 patients with vestibular neuritis were retrospectively analyzed. All the patients underwent DHI evaluation and vHIT examination. They were divided into mild handicap group, moderate handicap group and severe handicap group according to DHI score. The correlations between the parameters of vHIT and DHI score were compared among the three groups. The important parameters of vHIT were compared including vestibulo-ocular reflex (VOR) gain, gain asymmetry ratio (GA), abnormal saccade dispersion (PR%). Results:Of the 46 patients, 10 were in the mild handicap group, 21 in the moderate handicap group, and 15 in the severe handicap group. ①In the comparison of the mean value of lateral semicircular canal VOR gain, the vHIT gain of patients with mild, moderate and severe handicap were 0.64±0.06, 0.53±0.11 and 0.37±0.10, respectively, the mean value of VOR gain was negatively correlated with DHI score among the three groups(r=-0.545, P<0.001), and the pairwise comparisons among the three groups was statistically significant(P<0.05). In comparison of the mean values of lateral semicircular canal GA, the GA values of mild, moderate and severe handicap groups were 46.40±21.81, 47.59±15.17 and 56.57±17.39, respectively, there was no significant linear correlation between GA values and DHI scores among the three groups(r=0.246, P>0.05), there was no significant difference between the three groups(P>0.05). In comparison of the mean PR% of the lateral semicircular canal, the mean PR% of patients with mild, moderate and severe handicap group were 32.00±10.62, 53.82±17.09 and 76.00±10.01, respectively, PR% was positively correlated with DHI score(r=0.726, P<0.001), and the comparison among the three groups was statistically significant(P<0.05). ②The vertical semicircular canal vHIT gain of patients with mild, moderate and severe handicap was 0.63±0.06, 0.52±0.15 and 0.38±0.16, respectively, the mean of VOR gain was negatively correlated with DHI score among the three groups(r=-0.487, P<0.01), the comparison of mild-severe and moderate-severe group was statistically significant(P<0.05), while there was no significant difference between the mild and moderate group(P>0.05). In the comparison of the mean values of vertical semicircular canal GA, the GA values of mild, moderate and severe handicap groups were 40.40±15.31, 46.10±19.59 and 47.87±18.05, respectively, there was no significant linear correlation between GA values and DHI scores among the three groups(r=0.047, P>0.05), there was no significant difference in GA among the three groups(P>0.05). The PR% of patients with mild, moderate and severe handicap were 42.40±15.39, 54.14±17.60 and 64.93±10.95, respectively, there was a positive significant correlation between PR% and DHI score(r=0.454, P<0.05), there was statistically significant in the comparison of mild-severe group(P<0.05), while there was no statistical significance between the other groups(P>0.05). Conclusion:The VOR gain and PR% value of vHIT in patients with vestibular neuritis are closely related to the DHI score, which can evaluate the vestibular function and the degree of vertigo.


Assuntos
Teste do Impulso da Cabeça , Neuronite Vestibular , Humanos , Neuronite Vestibular/diagnóstico , Estudos Retrospectivos , Reflexo Vestíbulo-Ocular , Vertigem/diagnóstico , Canais Semicirculares , Hiperplasia
11.
Cell ; 185(23): 4409-4427.e18, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36368308

RESUMO

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Transtorno do Espectro Autista/genética , Predisposição Genética para Doença , Variações do Número de Cópias de DNA/genética , Genômica
12.
Artigo em Inglês | MEDLINE | ID: mdl-36378338

RESUMO

BACKGROUND: This study aimed to observe the changes in the ocular surface after phacoemulsification in patients with age-related cataracts with respect to the addition of varying concentrations of hyaluronate. METHODS: Patients with dry eye syndrome were treated with 0.3% and 0.1% sodium hyaluronate eye drops to evaluate the clinical improvement in each treatment group. A total of 73 patients (91 eyes) with age-related cataracts suffering from dry eye syndrome after phacoemulsification were divided into treatment group A (30 eyes), undergoing conventional therapy and treatment with 0.3% sodium hyaluronate; treatment group B (31 eyes), undergoing conventional therapy and treatment with 0.1% sodium hyaluronate; and the control group (group C; 30 eyes), undergoing conventional therapy only. Two groups were given different concentrations of sodium hyaluronate eye drops four times a day (should be completed between 8 AM and 8 PM), one drop at a time. RESULTS: Seven days, 2 weeks, 1 month, and 2 months postoperatively, there were significant differences in the Schirmer I test (SIt), first noninvasive tear film break-up time (NIBUTf), average noninvasive tear film break-up time (NIBUTav), tear meniscus height (TMH), and irregularity (when the refractive force of different parts of different meridians on the same meridian is different. The main manifestation is that the two meridians on the anterior surface of the cornea do not show a 90-degree vertical distribution, which cannot be corrected by conventional astigmatism lenses) between the three groups (p < 0.05). When compared with group C, there were significant differences in the SIt, NIBUTf, NIBUTav, TMH, and irregularity of group A and group B (p < 0.05). When compared with group B, there were significant improvements in the SIt, NIBUTf, NIBUTav, and TMH in group A (p < 0.05). CONCLUSIONS: In the early stage after phacoemulsification, the stability of the tear film is reduced. Adding sodium hyaluronate eye drops can restore tear film structure and improve corneal surface regularity, and a 0.3% solution of sodium hyaluronate eye drops is more effective than a 0.1% solution.

13.
Appl Environ Microbiol ; : e0155122, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36374022

RESUMO

Enterococcus faecalis is an important intestinal colonizing bacteria and can cause various tissue infections, including invasive blood infection (BI). The annual incidence of E. faecalis BI has been estimated to be ~4.5 per 100,000, with a fatality rate that can reach 20%. However, whether bacterial colonization or invasive infections are tissue based has not been thoroughly studied. In this study, we analyzed 537 clinical isolates from 7 different tissues to identify the key genomic elements that facilitate the colonization and invasive infection of E. faecalis. Comparative genomic analysis revealed that the BI E. faecalis isolates had the largest genome size but the lowest GC content, fsr quorum-sensing system genes were enriched in the BI E. faecalis, and the fsr gene cluster could enhance biofilm formation and serum resistance ability. Our findings also provide deep insight into the genomic differences between different tissue isolates, and the fsr quorum-sensing systems could be a key factor promoting E. faecalis invasion into the blood. IMPORTANCE First, we conducted an advanced study on the genomic differences between colonizing and infecting E. faecalis, which provides support and evidence for early and accurate diagnoses. Second, we discovered that fsr was significantly associated with blood infections, which also provides additional information for studies exploring the invasiveness of E. faecalis. Most importantly, we found that fsr played an important role in both biofilm formation and serum resistance ability in E. faecalis.

14.
Pharm Biol ; 60(1): 2253-2265, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36428240

RESUMO

CONTEXT: Rongjin Niantong Fang (RJNTF) is a Traditional Chinese Medicine formulation with a good therapeutic effect on osteoarthritis (OA). However, the underlying mechanisms remain unclear. OBJECTIVE: This study investigates whether RJNTF could delay OA cartilage degeneration by regulating the SDF-1/CXCR4-p38MAPK signalling pathway. MATERIALS AND METHODS: The Sprague-Dawley (SD) rats were used to establish the OA model by a modified Hulth's method. SD rats were divided into three groups (n = 10): blank group, model group (0.9% saline, 10 mL/kg/day), and treatment group (RJNTF, 4.5 g/kg/day). After 12 weeks of treatment, each group was analysed by H&E, Safranine-O solid green, ELISA, Immunohistochemistry, and Western blot. An in vitro model was induced with 100 ng/mL SDF-1 by ELISA, the blank group, model group, RJNTF group, and inhibitor group with intervention for 12 h, each group was analysed by Immunofluorescence staining and Western blot. RESULTS: SDF-1 content in the synovium was reduced in RJNTF treatment group compared to non-treatment model group (788.10 vs. 867.32 pg/mL) and down-regulation of CXCR4, MMP-3, MMP-9, MMP-13 protein expression, along with p38 protein phosphorylated were observed in RJNTF treatment group. In vitro results showed that RJNTF (IC50 = 8.925 mg/mL) intervention could down-regulate SDF-1 induced CXCR4 and p38 protein phosphorylated and reduce the synthesis of MMP-3, MMP-9, and MMP-13 proteins of chondrocytes from SD rat cartilage tissues. DISCUSSION AND CONCLUSION: RJNTF alleviates OA cartilage damage by SDF-1/CXCR4-p38MAPK signalling pathway inhibition. Our ongoing research focuses on Whether RJNTF treats OA through alternative pathways.


Assuntos
Cartilagem Articular , Osteoartrite , Ratos , Animais , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/farmacologia , Metaloproteinase 3 da Matriz/uso terapêutico , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 13 da Matriz , Ratos Sprague-Dawley , Osteoartrite/tratamento farmacológico , Receptores CXCR4/metabolismo , Receptores CXCR4/uso terapêutico
15.
J Clin Epidemiol ; 153: 1-12, 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36351510

RESUMO

BACKGROUND AND OBJECTIVES: To evaluate and map the reporting and methodological quality of network meta-analysis (NMA) on acupuncture. METHODS: Published acupuncture NMAs were searched through eight databases from inception to February 2022. The reporting and methodological quality of included studies was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analysis (PRISMA-NMA) statement and the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist. RESULTS: A total of 113 NMAs were identified. Most (99, 87.61%) studies were performed in China. Most studies focused on multiple acupuncture techniques (82.30%), and the main studied ailments were pain and poststroke sequelae (20.24%). The median (interquartile range (IQR)) score of the reporting quality was 26.5 (25-28.5). However, poor reporting rates in the protocol and registration (33.63%) and geometry of the network (35.40%), especially for China-based studies, were identified. The methodological quality of only 2 (1.77%) English studies was high. The reporting rate of Chinese studies was below 15% on each of items 4, 7, 10, and 12. CONCLUSION: The reporting quality of the NMAs was moderate, but the methodological quality was very low. The reporting and methodological quality of future NMAs, especially for Chinese studies, need further improvement.

16.
World J Diabetes ; 13(11): 986-1000, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36437866

RESUMO

BACKGROUND: Diabetic retinopathy (DR) is the driving force of blindness in patients with type 2 diabetes mellitus (T2DM). DR has a high prevalence and lacks effective therapeutic strategies, underscoring the need for early prevention and treatment. Yunnan province, located in the southwest plateau of China, has a high pre-valence of DR and an underdeveloped economy. AIM: To build a clinical prediction model that will enable early prevention and treatment of DR. METHODS: In this cross-sectional study, 1654 Han population with T2DM were divided into groups without (n = 826) and with DR (n = 828) based on fundus photography. The DR group was further subdivided into non-proliferative DR (n = 403) and proliferative DR (n = 425) groups. A univariate analysis and logistic regression analysis were conducted and a clinical decision tree model was constructed. RESULTS: Diabetes duration ≥ 10 years, female sex, standing- or supine systolic blood pressure (SBP) ≥ 140 mmHg, and cholesterol ≥ 6.22 mmol/L were risk factors for DR in logistic regression analysis (odds ratio = 2.118, 1.520, 1.417, 1.881, and 1.591, respectively). A greater severity of chronic kidney disease (CKD) or hemoglobin A 1c increased the risk of DR in patients with T2DM. In the decision tree model, diabetes duration was the primary risk factor affecting the occurrence of DR in patients with T2DM, followed by CKD stage, supine SBP, standing SBP, and body mass index (BMI). DR classification outcomes were obtained by evaluating standing SBP or BMI according to the CKD stage for diabetes duration < 10 years and by evaluating CKD stage according to the supine SBP for diabetes duration ≥ 10 years. CONCLUSION: Based on the simple and intuitive decision tree model constructed in this study, DR classification outcomes were easily obtained by evaluating diabetes duration, CKD stage, supine or standing SBP, and BMI.

17.
Cell Rep ; 41(6): 111609, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36351400

RESUMO

Bacterial type IV secretion systems (T4SSs) are the specific devices that mediate the dissemination of antibiotic resistant genes via horizontal gene transfer (HGT). Multi-drug-resistant Enterococcus faecalis (E. faecalis) represents a clinical public health threat because of its transferable plasmid with a functional plasmid-encoded (PE)-T4SS. Here, we report a chromosome-encoded (CE)-T4SS that exists in 40% of E. faecalis isolates. Compared with the PE-T4SS, CE-T4SS displays distinct characteristics in protein architecture and is capable of mediating large and genome-wide gene transfer in an imprecise manner. Reciprocal exchange of CE-T4SS- or PE-T4SS-associated origin of transfer (oriT) could disrupt HGT function, indicating that CE-T4SS is an independent system compared with PE-T4SS. Taken together, the CE-T4SS sheds light on the knowledge of HGT in gram-positive bacteria and triggers us to explore more evolutionary mechanisms in E. faecalis.


Assuntos
Enterococcus faecalis , Transferência Genética Horizontal , Enterococcus faecalis/genética , Enterococcus faecalis/metabolismo , Transferência Genética Horizontal/genética , Plasmídeos/genética , Sistemas de Secreção Tipo IV/metabolismo , Cromossomos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
18.
Comput Intell Neurosci ; 2022: 9917691, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387767

RESUMO

Accurate retinal blood vessels segmentation is an important step in the clinical diagnosis of ophthalmic diseases. Many deep learning frameworks have come up for retinal blood vessels segmentation tasks. However, the complex vascular structure and uncertain pathological features make blood vessel segmentation still very challenging. This paper proposes a novel multimodule concatenation via a U-shaped network for retinal vessels segmentation, which is based on atrous convolution and multikernel pooling. The proposed network structure retains three layers of the essential structure of U-Net, in which the atrous convolution combining the multikernel pooling blocks are designed to obtain more contextual information. The spatial attention module is concatenated with the dense atrous convolution module and the multikernel pooling module to form a multimodule concatenation. And different dilation rates are selected by cascading to acquire a larger receptive field in atrous convolution. Adequate comparative experiments are conducted on these public retinal datasets: DRIVE, STARE, and CHASE_DB1. The results show that the proposed method is effective, especially for microvessels. The code will be released at https://github.com/rocklijun/MC-UNet.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Vasos Retinianos/diagnóstico por imagem , Retina
19.
Quant Imaging Med Surg ; 12(10): 4758-4770, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36185061

RESUMO

Background: This study set out to develop a computed tomography (CT)-based wavelet transforming radiomics approach for grading pulmonary lesions caused by COVID-19 and to validate it using real-world data. Methods: This retrospective study analyzed 111 patients with 187 pulmonary lesions from 16 hospitals; all patients had confirmed COVID-19 and underwent non-contrast chest CT. Data were divided into a training cohort (72 patients with 127 lesions from nine hospitals) and an independent test cohort (39 patients with 60 lesions from seven hospitals) according to the hospital in which the CT was performed. In all, 73 texture features were extracted from manually delineated lesion volumes, and 23 three-dimensional (3D) wavelets with eight decomposition modes were implemented to compare and validate the value of wavelet transformation for grade assessment. Finally, the optimal machine learning pipeline, valuable radiomic features, and final radiomic models were determined. The area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve were used to determine the diagnostic performance and clinical utility of the models. Results: Of the 187 lesions, 108 (57.75%) were diagnosed as mild lesions and 79 (42.25%) as moderate/severe lesions. All selected radiomic features showed significant correlations with the grade of COVID-19 pulmonary lesions (P<0.05). Biorthogonal 1.1 (bior1.1) LLL was determined as the optimal wavelet transform mode. The wavelet transforming radiomic model had an AUC of 0.910 in the test cohort, outperforming the original radiomic model (AUC =0.880; P<0.05). Decision analysis showed the radiomic model could add a net benefit at any given threshold of probability. Conclusions: Wavelet transformation can enhance CT texture features. Wavelet transforming radiomics based on CT images can be used to effectively assess the grade of pulmonary lesions caused by COVID-19, which may facilitate individualized management of patients with this disease.

20.
Int J Endocrinol ; 2022: 6073911, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186658

RESUMO

Diabetic nephropathy (DN) has become the most common secondary kidney disease causing end-stage renal disease (ESRD). Nevertheless, the underlying mechanisms responsible for DN remain largely unknown. Regulated in development and DNA damage response 1 (REDD1) is a prooxidative molecule known to contribute to diabetes mellitus and its complications. However, it has not been previously examined whether and how REDD1 can further drive renal tubular epithelial cell (RTEC) apoptosis and epithelial-to-mesenchymal transition in DN. The expression of REDD1 was elevated in the kidneys of DN patients and diabetic mice in this study. By generating the DN model in REDD1 knockout mice, we demonstrated that REDD1 deficiency significantly improved apoptosis and EMT in diabetic mice. In vitro experiments showed that REDD1 generation was induced by high glucose (HG) in HK-2 cells. Similarly, the transfection of REDD1 siRNA plasmid also suppressed HG-induced apoptosis and EMT. Furthermore, we discovered that the inhibition of REDD1 suppressed the expression of Nox4-induced HG and reactive oxygen species (ROS) synthesis in HK-2 cells. In addition, HG could induce endogenous REDD1 and TXNIP to form a powerful complex. In summary, our findings demonstrate that blocking the REDD1/TXNIP complex can prevent HG-induced apoptosis and EMT by inhibiting ROS production, highlighting REDD1 as a valuable therapeutic priority site for DN.

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