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1.
Immunobiology ; 227(3): 152223, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35552111

RESUMO

The present study intends to clarify the hypothesis that PVL-positive Methicillin-resistant S. aureus strain (PVL+-MRSA)-infected macrophages regulate autophagy and thus in turn inhibit phagocytosis through the in vitro and in vivo experiments. The autophagy of mouse macrophage cell line RAW264.7 was observed by fluorescence microscopy, and counted based on the number of each cell dot-like structure GFP-LC3. The protein levels of the phagocytic factors associated with autophagy were determined by western blotting. The phagocytosis of RAW264.7 on MRSA was determined by counting the colony. The clinically isolated and identified PVL+-MRSA strain was used to infect BALB/c mice (left nasal drip) to establish a mouse pneumonia model. PVL+-MRSA mice were then treated with 3-MA or linezolid. Bronchoalveolar lavage fluid (BALF) from mice was collected for macrophage counting by Flow cytometry assay. The right lung was aseptically isolated for counting the amount of bacteria. The results showed that PVL+-MRSA could induced the autophagy of macrophages, which in turn reduced the damage from macrophages, which were respectively alleviated by 3-MA and aggravated by rapamycin. Exogenous rPVL administrated into PVL--MRSA-infected macrophages caused the autophagy of macrophage. Exogenous rPVL, particularly A-Luk S-PV, administrated into macrophages also caused the autophagy of macrophage, which was reversed by PMX53, a C5aR antagonist. In a mouse pneumonia model, PVL+-MRSA could induced the autophagy of macrophages, which in turn reduced the damage from macrophages, which were respectively alleviated by 3-MA or linezolid. In conclusion, this study indicated PVL+-MRSA regulated macrophage autophagy, which in turns inhibit the phagocytosis of S. aureus by macrophage. This study may provide a potential target against S. aureus infection.

2.
Front Endocrinol (Lausanne) ; 13: 790586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432212

RESUMO

Discriminating between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) can help provide more specific treatments. However, there are no ideal biomarkers for their differentiation. Thus, the aim of this study was to identify biomarkers for diagnosing and predicting the progression of DN by investigating different salivary glycopatterns. Lectin microarrays were used to screen different glycopatterns in patients with DN or NDRD. The results were validated by lectin blotting. Logistic regression and artificial neural network analyses were used to construct diagnostic models and were validated in in another cohort. Pearson's correlation analysis, Cox regression, and Kaplan-Meier survival curves were used to analyse the correlation between lectins, and disease severity and progression. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analyses were used to identify corresponding glycoproteins and predict their function. Both the logistic regression model and the artificial neural network model achieved high diagnostic accuracy. The levels of Aleuria aurantia lectin (AAL), Lycopersicon esculentum lectin (LEL), Lens culinaris lectin (LCA), Vicia villosa lectin (VVA), and Narcissus pseudonarcissus lectin (NPA) were significantly correlated with the clinical and pathological parameters related to DN severity. A high level of LCA and a low level of LEL were associated with a higher risk of progression to end-stage renal disease. Glycopatterns in the saliva could be a non-invasive tool for distinguishing between DN and NDRD. The AAL, LEL, LCA, VVA, and NPA levels could reflect the severity of DN, and the LEL and LCA levels could indicate the prognosis of DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Biomarcadores , Cromatografia Líquida , Nefropatias Diabéticas/diagnóstico , Feminino , Humanos , Lectinas , Masculino , Prognóstico , Espectrometria de Massas em Tandem
3.
Front Oncol ; 12: 844067, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433467

RESUMO

Objectives: Metachronous liver metastasis (LM) significantly impacts the prognosis of stage I-III colorectal cancer (CRC) patients. An effective biomarker to predict LM after surgery is urgently needed. We aimed to develop deep learning-based models to assist in predicting LM in stage I-III CRC patients using digital pathological images. Methods: Six-hundred eleven patients were retrospectively included in the study and randomly divided into training (428 patients) and validation (183 patients) cohorts according to the 7:3 ratio. Digital HE images from training cohort patients were used to construct the LM risk score based on a 50-layer residual convolutional neural network (ResNet-50). An LM prediction model was established by multivariable Cox analysis and confirmed in the validation cohort. The performance of the integrated nomogram was assessed with respect to its calibration, discrimination, and clinical application value. Results: Patients were divided into low- and high-LM risk score groups according to the cutoff value and significant differences were observed in the LM of the different risk score groups in the training and validation cohorts (P<0.001). Multivariable analysis revealed that the LM risk score, VELIPI, pT stage and pN stage were independent predictors of LM. Then, the prediction model was developed and presented as a nomogram to predict the 1-, 2-, and 3-year probability of LM. The integrated nomogram achieved satisfactory discrimination, with C-indexes of 0.807 (95% CI: 0.787, 0.827) and 0.812 (95% CI: 0.773, 0.850) and AUCs of 0.840 (95% CI: 0.795, 0.885) and 0.848 (95% CI: 0.766, 0.931) in the training and validation cohorts, respectively. Favorable calibration of the nomogram was confirmed in the training and validation cohorts. Integrated discrimination improvement and net reclassification index indicated that the integrated nomogram was superior to the traditional clinicopathological model. Decision curve analysis confirmed that the nomogram has clinical application value. Conclusions: The LM risk score based on ResNet-50 and digital HE images was significantly associated with LM. The integrated nomogram could identify stage I-III CRC patients at high risk of LM after primary colectomy, so it may serve as a potential tool to choose the appropriate treatment to improve the prognosis of stage I-III CRC patients.

4.
ACS Appl Mater Interfaces ; 14(18): 21474-21485, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35486453

RESUMO

Multiresponsive and high-performance flexible actuators with a simple configuration, high mechanical strength, and low-power consumption are highly desirable for soft robotics. Here, a novel mechanically robust and multiresponsive Ti3C2Tx MXene-based actuator with high actuation performance via dual-mechanism synergistic effect driven by the hygroexpansion of bacterial cellulose (BC) layer and the thermal expansion of biaxially oriented polypropylene (BOPP) layer is developed. The actuator is flexible and shows an ultrahigh tensile strength of 195 MPa. Unlike the conventional bimorph-structured actuators based on a single-mechanism, the actuator developed provides a favorable architecture for dual-mechanism synergism, resulting in exceptionally reversible actuation performance under electricity and near-infrared (NIR) light stimuli. Typically, the developed actuator can produce the largest bending angle (∼400°) at the lowest voltage (≤4 V) compared with that reported previously for single mechanism soft actuators. Furthermore, the actuator also can be driven by a NIR light at a 2 m distance, displaying an excellent long-distance photoresponsive property. Finally, various intriguing applications are demonstrated to show the great potential of the actuator for soft robotics.

5.
Int J Biol Macromol ; 209(Pt A): 1368-1378, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35461868

RESUMO

Microbiota in the oral cavity plays an important role in maintaining human health. Our previous studies have revealed significant alterations of salivary glycopatterns in gastric cancer (GC) patients, but it is unclear whether these altered salivary glycopatterns can cause the dysbiosis of oral microbiota. In this study, the oral microbiome of healthy volunteers (HVs) and GC patients were detected. The neoglycoproteins were then synthesized according to the altered glycopatterns in GC patients and used to explore the effects of specific salivary glycopattern against oral microbiota. The results showed that five species were significantly increased (p < 0.05) while two species were significantly decreased (p < 0.01) in the saliva of GC patients compared with that of HVs. And the fucose-neoglycoproteins (30-100 µg/mL) could reduce the adhesion and toxicity of Aggregatibacter segnis (A. segnis) to oral cells (HOEC and CAL-27), change the glycan structures of lipopolysaccharide on the surface of A. segnis, and enhance the capacity of A. segnis to trigger innate immune responses. This study revealed that the changes of salivary protein glycopatterns in GC patients might contribute to the dysbiosis of oral microbiota, and had important implications in developing new carbohydrate drugs to maintain a balanced microbiota in the oral.

6.
Adv Sci (Weinh) ; : e2105391, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35343654

RESUMO

The subcellular localization and intracellular trafficking of Toll-like receptors (TLRs) critically regulate TLRs-mediated antimicrobial immunity and autoimmunity. Here, it is demonstrated that the E3 ubiquitin ligase RNF115 inhibits the post-endoplasmic reticulum (ER) trafficking of TLRs and TLRs-mediated immune responses by catalyzing ubiquitination of the small GTPases RAB1A and RAB13. It is shown that the 14-3-3 chaperones bind to AKT1-phosphorylated RNF115 and facilitate RNF115 localizing on the ER and the Golgi apparatus. RNF115 interacts with RAB1A and RAB13 and catalyzes K11-linked ubiquitination on the Lys49 and Lys61 residues of RAB1A and on the Lys46 and Lys58 residues of RAB13, respectively. Such a modification impairs the recruitment of guanosine diphosphate (GDP) dissociation inhibitor 1 (GDI1) to RAB1A and RAB13, a prerequisite for the reactivation of RAB proteins. Consistently, knockdown of RAB1A and RAB13 in Rnf115+/+ and Rnf115-/- cells markedly inhibits the post-ER and the post-Golgi trafficking of TLRs, respectively. In addition, reconstitution of RAB1AK49/61R or RAB13K46/58R into Rnf115+/+ cells but not Rnf115-/- cells promotes the trafficking of TLRs from the ER to the Golgi apparatus and from the Golgi apparatus to the cell surface, respectively. These findings uncover a common and step-wise regulatory mechanism for the post-ER trafficking of TLRs.

7.
J Nanobiotechnology ; 20(1): 97, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35236339

RESUMO

BACKGROUND: Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. RESULTS: The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. CONCLUSIONS: Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing.


Assuntos
Diabetes Mellitus Experimental , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Animais , Proliferação de Células , Exossomos/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos
8.
J Mater Chem B ; 10(13): 2171-2182, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35265955

RESUMO

Bacterial infections remain a major concern during wound healing and tissue bonding. The excessive proliferation of bacteria will seriously hinder the repair of the wound and even lead to death. Generally, surgical sutures might cause damage to the surrounding tissues and inevitable infection due to the unfixed shape of the wound. Thus, it is urgent to develop novel antibacterial skin dressing with self-healing and strong adhesion properties. Herein, we prepared an antibacterial and self-healable hydrogel with strong adhesion activity through natural small molecules, including thioctic acid TA and gentamicin (GM). The rapid ring-opening-polymerization of the TA (PTA) forms the backbone of macromolecules, and the functional hydrogel was constructed with the crosslinking of GM, termed as G-PTA, which offers hydrogen bonding interactions between the amino and hydroxyl groups of GM and carboxylic group side chains of poly(TA). The synthesized hydrogel exhibited rapid self-healing ability and strong tissue adhesion due to the internal dynamic disulfide bonds and multiple hydrogen bonds. Importantly, the introduction of GM enabled the G-PTA hydrogel to sustainably release antibiotics and exhibit a durative antibacterial effect with the degradation of PTA, which further shorten the therapeutic time and enhance tissue regeneration in a wound infection model. The in vitro and in vivo experiments demonstrate that the G-PTA hydrogel has potential as a surgical antibacterial biological adhesive, especially for bacterial wound infections.


Assuntos
Ácido Tióctico , Infecção dos Ferimentos , Gentamicinas/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização
9.
BMC Psychiatry ; 22(1): 143, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193538

RESUMO

BACKGROUND: Alcohol dependence is a mental disorder with a high relapse rate. However, specific neuroimaging biomarkers have not been determined for alcohol dependence and its relapse. We conducted data-driven research to investigate resting-state functional magnetic resonance imaging (rs-fMRI) during early abstinence from alcohol dependence and its potential ability to predict relapse. METHODS: Participants included 68 alcohol-dependent patients and 68 healthy controls (HCs). The regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) were compared between the alcohol dependence group and the HCs and between the relapse group and the nonrelapse group. The brain regions that presented significantly different ReHo and/or fALFF between the alcohol-dependent patients and HCs and/or between the relapsed and nonrelapsed patients were selected as the seeds to calculate the functional connectivities (FCs). RESULTS: During a 6-month follow-up period, 52.24% of alcohol-dependent patients relapsed. A regression model for differentiating alcohol-dependent patients and HCs showed that reductions in ReHo in the left postcentral region, fALFF in the right fusiform region, and FC in the right fusiform region to the right middle cingulum were independently associated with alcohol dependence, with an area under the receiver operating characteristic curve (AUC) of 0.841. The baseline FC of the left precentral to the left cerebellum of the relapse group was significantly lower than that of the nonrelapse group. The AUC of this FC to predict relapse was 0.774. CONCLUSIONS: Our findings contribute to advancing research on the neurobiological etiology and predictive biomarkers for relapse associated with alcohol dependence.


Assuntos
Alcoolismo , Alcoolismo/diagnóstico por imagem , Encéfalo , Mapeamento Encefálico/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Recidiva
10.
Medicine (Baltimore) ; 101(4): e28648, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35089205

RESUMO

BACKGROUND: The aim of this study was to observe the anti-infective effect of the distal femoral tumor prosthesis coated with antibiotic cement during limb salvage treatment, and evaluate its potential prospect in clinic. METHODS: In this randomized controlled trial, the en bloc resection and reconstruction were performed in 36 patients with distal femoral primary bone tumor. Patients were divided into 2 groups randomly according to the application of antibiotic bone cement coating, which included antibiotic cement coating group (16 cases) and control group (18 cases). There were 10 men and 6 women in anti-infection group, aged from 18 to 54 years (23.47 ±â€Š3.53), and there were 12 men and 6 women in control group, aged from 19 to 56 years (24.16 ±â€Š4.32). The tumor type, age, sex, and Enneking stage were enrolled with well-matched of the 2 groups of patients. There was no difference between bundles and routine standard care for each group. The antibiotic cement was coated on the surface of polyethylene jacket with punched holes during operation. The peri-prosthetic infection, local recurrence and distant metastasis were followed up and limb functions were evaluated by Musculoskeletal Tumor Society 93 (MSTS93) scoring system. RESULTS: Patients were followed up till 34.7 months (range 18∼62 months). There was no periprosthetic infection in anti-infection group. Four cases in control group showed deep infection. Infection rate had significant differences between the 2 groups (P < .05). Infection-related prosthesis mortality was 0% (0/16) in anti-infection group and 16.67% (3/18) in control group. Local recurrence and distant metastasis occurred in 7 of 34 patients with primary malignant bone tumor, wherein 2 cases of local recurrence and 1 cases of distant metastasis occurred in anti-infective group; 2 cases of local recurrence and 2 cases of distant metastasis occurred in the control group. During a latest follow-up, MSTS93 function scoring revealed a mean of 25.6 ±â€Š4.2 in anti-infection group and 18.5 ±â€Š3.3 in control group. The survival rate of anti-infective group is 75%, and the survival rate of control group is 61.11%. CONCLUSION: The antibiotic cement-coated technique on the surface of the polyethylene jacket of custom-made distal femoral prosthesis is simple and effective in controlling the periprosthetic infection after tumor prosthesis reconstruction.


Assuntos
Antibacterianos/uso terapêutico , Cimentos Ósseos/uso terapêutico , Neoplasias Ósseas/cirurgia , Neoplasias Femorais/cirurgia , Salvamento de Membro/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenos , Complicações Pós-Operatórias/terapia , Implantação de Prótese/métodos , Infecções Relacionadas à Prótese/terapia , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento
11.
Front Psychiatry ; 13: 858675, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35492731

RESUMO

Objective: The interleukin-8 (IL-8) has been reported to play an important role in depression, which might be modulated by the selective serotonin reuptake inhibitors (SSRIs). Thus, the aim of this study was to investigate serum IL-8 levels, depressive symptom, and their associations in drug-free MDD patients, MDD patients with SSRIs, and healthy controls (HCs). Methods: Fifty-seven drug-free MDD patients (male/female = 35/22, mean age: 39.24 years), 30 MDD patients with SSRIs (male/female = 11/19, mean age: 39.73 years), and 101 HCs (male/female = 52/49, mean age: 37.38 years) were recruited in this cross-sectional study. Serum IL-8 levels and depressive symptom were assessed using the Flow Cytometer and Hamilton Depression Scale (HAMD). The analysis of variance was used for the comparison between groups. The relationship between serum log10 IL-8 levels and HAMD score was analyzed by Pearson correlation. Results: Serum log10IL-8 levels were lower in all patients than HCs after controlling for covariates (F = 4.86, p = 0.03). There was significant difference in serum Log10IL-8 levels among three groups after controlling for covariates (F = 14.63, p < 0.001). Serum Log10IL-8 levels in drug-free patients were lower compared to HCs (F = 19.38, p < 0.001) or patients with SSRIs (F = 21.89, p < 0.001) after controlling for covariates. However, there was not difference in serum log10IL-8 levels between patients with SSRIs and HCs after controlling for covariates. Moreover, serum Log10IL-8 levels were negatively correlated with HAMD score in all patients (r = -0.37, p = 0.02). Also, serum Log10IL-8 levels were negatively correlated with HAMD score in drug-free patients (r = -0.74, p = 0.01), but not in patients with SSRIs. Conclusion: Our data supported that the decline in serum IL-8 levels was association with depression. Moreover, the SSRIs might modulate increased serum IL-8 levels of depression.

12.
J Affect Disord ; 299: 416-424, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34906641

RESUMO

BACKGROUND: Internet addiction (IA) is associated with adverse consequences, especially for younger people. Evidence indicates that IA is associated with depression, but no studies have yet investigated potential common vulnerability between them. METHODS: IA (measured by the Young's 20-item Internet Addiction Test Scale) and depressive symptoms (measured by the Patient Health Questionnaire-9 Scale) among 12 043 undergraduates were surveyed at baseline and at a respective 12 month follow-up for each participant. Application of a cross-lagged panel model approach (CLPM) revealed an association between IA and depression after adjusting for demographic variables. RESULTS: Rates of baseline IA and depression were 5.47% (95% CI: 5.07%, 5.88%) and 3.85% (95% CI: 3.51%, 4.20%), respectively; increasing to 9.47% (95% CI: 8.94%, 9.99%) and 5.58% (95% CI: 5.17%,5.99%), respectively, at follow-up. Rates of new-incidences of IA and depression over 12 months were 7.43% (95% CI: 6.95%, 7.91%) and 4.47% (95% CI: 4.09%, 4.84%), respectively. Models in the present analysis revealed that baseline depression had a significant net-predictive effect on follow-up IA, and baseline IA had a significant net-predictive effect on follow-up depression. LIMITATIONS: The follow-up survey response rate was moderate (54.69%) in this analysis of university students. Moreover, the IAT-20 scale did not allow differentiate between specific forms of Internet activity. CONCLUSIONS: Common vulnerability and bidirectional cross-causal effects may both contribute to the association between IA and depression, with common vulnerability likely playing a more significant role than cross-causal effects.


Assuntos
Comportamento Aditivo , Universidades , Comportamento Aditivo/epidemiologia , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Humanos , Internet , Transtorno de Adição à Internet , Estudos Longitudinais , Estudantes
13.
Acta Biomater ; 140: 338-349, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896631

RESUMO

Antimicrobial coatings are one of the most promising strategies to prevent bacterial infections in orthopedic and dental implants. Combining antimicrobial agents with different antimicrobial mechanisms might have synergistic effects and be more potent. Others have shown that nanocomposites of silver nanoparticles (AgNPs) decorated with antimicrobial peptides (AMPs) show increased potency as free agents in solution. However, similar nanocomposites have not been explored to coat biomaterials through cooperative weak electrostatic attraction forces between AMP, AgNPs and substrates in need of protection against infection. In this work, we synthesized self-assembled antimicrobial amphiphiles of an AMP, GL13K. Then, we decorated the AMP nanostructures with AgNPs, which were finally used to coat etched Ti (eTi) surfaces. The strong hydrogen bonding between the AMP amphiphiles and the polar eTi yielded a robust and stable coating. When compared to single AgNP or single AMP coatings, our hybrid nanocoatings had notably higher in vitro antimicrobial potency against multiple bacteria strains related to implant infection. The hybrid coating also showed relevant antimicrobial activity in an in vivo subcutaneous infection model in rats. This work advances the application of AgNP/AMP nanocomposites as effective coatings for prevention of implant infections. STATEMENT OF SIGNIFICANCE: High morbidity, mortality and elevated costs are associated with orthopedic and dental implant infections. Conventional antibiotic treatment is ineffective due to barrier-like extracellular polymeric substances in biofilms and the increasing threat from antibiotic resistance. Antimicrobial coatings are one of the most promising strategies, but the performance is usually unsatisfactory, especially when tested in vivo. Here, we present a hybrid nanocoating with different modes of action to prevent implant infections using self-assembled antimicrobial peptide (AMP) amphiphiles decorated with silver nanoparticles (AgNPs). When compared to single AgNP or AMP coatings, our hybrid nanocoatings showed significant increases in antimicrobial potency against multiple implant infection-related bacterial strains in vitro and in an in vivo rat subcutaneous infection model.


Assuntos
Materiais Revestidos Biocompatíveis , Nanopartículas Metálicas , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Nanopartículas Metálicas/química , Ratos , Prata/química , Prata/farmacologia
14.
Front Cell Dev Biol ; 9: 750948, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869337

RESUMO

Previous studies have found that the novel low-elastic-modulus Ti2448 alloy can significantly reduce stress shielding and contribute to better bone repair than the conventional Ti6Al4V alloy. In this study, the promotion of osteogenesis and angiogenesis by three-dimensionally printed Ti2448 were also observed in vivo. However, these were not significant in a series of in vitro tests. The stiffness of materials has been reported to greatly affect the response of macrophages, and the immunological regulation mediated by macrophages directly determines the fate of bone implants. Therefore, we designed more experiments to explore the role of three-dimensionally printed Ti2448 in macrophage activation and related osteogenesis and angiogenesis. As expected, we found a significant increase in the number of M2 macrophages around Ti2448 implants, as well as better osteogenesis and angiogenesis in vivo. In vitro studies also showed that macrophages pre-treated with Ti2448 alloy significantly promoted angiogenesis and osteogenic differentiation through increased PDGF-BB and BMP-2 secretion, and the polarization of M2 macrophages was enhanced. We deduced that Ti2448 promotes angiogenesis and osteogenesis through Piezo1/YAP signaling axis-mediated macrophage polarization and related cytokine secretion. This research might provide insight into the biological properties of Ti2448 and provide a powerful theoretical supplement for the future application of three-dimensionally printed Ti2448 implants in orthopaedic surgery.

15.
Gen Psychiatr ; 34(6): e100632, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950853

RESUMO

BACKGROUND: Obsessive-compulsive disorder (OCD) is considered a very debilitating disorder with severe loss of quality of life and income. AIMS: This study estimates the quality of life and economic consequences of OCD in China. METHODS: The research team interviewed 639 patients with OCD in 13 hospitals in 12 cities in China. The direct method was used to get the direct cost of OCD. Indirect costs associated with OCD were estimated using the human capital approach. Linear regression analysis was conducted for quality of life and generalised linear model analysis was conducted for total cost. Sensitivity analysis was used to analyse the uncertainty of total cost. RESULTS: The mean quality of life score for OCD was 52.78 (20.46). The annual total cost of OCD per capita was 24 503.78 (95% CI: 22 621.53 to 26 386.03) renminbi (RMB) (US$3465.88 (95% CI: US$3199.65 to US$3732.11)). The annual cost of OCD in China was estimated to be 37.74 billion (95% CI: 34.95 billion to 40.53 billion) RMB (equal to US$5.34 billion (95% CI: US$4.94 billion to US$5.73 billion)). Sensitivity analysis showed that the total annual cost of OCD in China was between 23.15 billion RMB (US$3.27 billion) and 370.00 billion RMB (US$52.33 billion). Worse social function status, more psychiatric symptoms and higher Yale Brown Obsessive-Compulsive Scale (Y-BOCS) score were associated with worse quality of life. The numbers of clinic visits and hospitalisations, socioeconomic status, education, Y-BOCS scores and age were found to be significantly associated with total cost. CONCLUSIONS: OCD is associated with low quality of life and high costs in China. The findings call for concerted efforts to improve services for patients with OCD.Improvements may include early detection and diagnosis, the provision of evidence-based treatments and relapse prevention strategies.

16.
Oxid Med Cell Longev ; 2021: 5192271, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970416

RESUMO

Increasing evidence suggests that traditional Chinese medicine strategies are obviously beneficial for cancer treatment, but scientific research on the underlying molecular mechanisms is lacking. We report that ursolic acid, a bioactive ingredient isolated from Radix Actinidiae chinensis, has strong antitumour effects on osteosarcoma cells. Functional studies showed that ursolic acid inhibited tumour cell proliferation and promoted the apoptosis of a variety of osteosarcoma cells. Ursolic acid had a synergistic cytotoxic effect with cisplatin on osteosarcoma cells. In a mouse osteosarcoma xenograft model, low-dose cisplatin combined with ursolic acid significantly reduced tumour growth. Notably, ursolic acid reversed weight loss in mice treated with cisplatin. Mechanistic studies showed that ursolic acid degraded ferritin by activating autophagy and induced intracellular overload of ferrous ions, leading to ferroptosis. In addition, ursolic acid enhanced the DNA-damaging effect of cisplatin on osteosarcoma cells. Taken together, these findings suggest that ursolic acid is a nontoxic adjuvant that may enhance the effectiveness of chemotherapy in osteosarcoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Ferritinas/metabolismo , Osteossarcoma/tratamento farmacológico , Triterpenos/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose , Cisplatino/farmacologia , Modelos Animais de Doenças , Humanos , Camundongos , Triterpenos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
China CDC Wkly ; 3(29): 615-619, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34594947

RESUMO

WHAT IS ALREADY KNOWN ON THIS TOPIC?: Vibrio parahaemolyticus (V. parahaemolyticus) is frequently resistant to common antimicrobials such as ampicillin and generally highly susceptible to most clinically used antimicrobials. WHAT IS ADDED BY THIS REPORT?: V. parahaemolyticus were highly resistant to cefazolin and ampicillin: 94.4% and 37.0%, respectively. However, it was below 3% resistance to all 10 other antimicrobials including clinically relevant agents and even imipenem. The overall levels of antimicrobial resistance and multidrug resistance were 95.1% and 3.3%, respectively. The distribution of antimicrobial resistance and the multidrug resistance had regional, temporal, sexual, and isolated source strain variation. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: This study provides data on drug resistance of V. parahaemolyticus in Chinese clinical settings, which will help develop a public health strategy.

18.
Physiol Behav ; 242: 113626, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34673052

RESUMO

In addition to the antidepressant properties of ketamine at subanesthetic doses, studies have revealed ketamine's influence on memory acquisition, consolidation, and reconsolidation. The effects of acute low-dose ketamine administration on conditioned memory have been investigated extensively in rodents through conditioned fear memory and morphine-induced conditioned place preference. In contrast to conditioned memory, the novel object recognition (NOR) task assesses the natural format of memory by exploiting the rodents' natural preference for novelty. Acute low-dose ketamine administration impairs NOR acquisition and consolidation, but its influence on reconsolidation remains unclear. We investigated the issue as well as the involvement of BDNF/TrkB pathway in this process by administering ketamine (i.p., 10 mg/kg, immediately or 6 h after reactivation, or without reactivation) and ANA-12 (i.p., 0.5 mg/kg, 5 min after ketamine/vehicle administration). ANA-12 is a selective antagonist for the BDNF TrkB receptor. Ketamine administration, immediately after (rather than without) reactivation, significantly increased the NOR preference index, thus suggesting an enhanced memory reconsolidation rather than consolidation. Ketamine exerted no significant effect when administered 6 h after reactivation, thereby suggesting 6 h to be an effective time window. ANA-12 administration significantly reduced the ketamine-induced NOR preference index increase, thus suggesting that the blockage of ketamine improves NOR reconsolidation. However, this blockage had no significant effect on the ketamine-induced hippocampal BDNF level increase. In conclusion, acute low-dose ketamine administration improves NOR memory reconsolidation by increasing hippocampal BDNF levels and subsequent BDNF binding to the TrkB receptor.


Assuntos
Ketamina , Receptor trkB , Animais , Fator Neurotrófico Derivado do Encéfalo , Condicionamento Clássico , Ketamina/farmacologia , Glicoproteínas de Membrana , Memória , Camundongos , Proteínas Tirosina Quinases
19.
Shanghai Kou Qiang Yi Xue ; 30(4): 402-405, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34693434

RESUMO

PURPOSE: To investigate the changes of α-smooth muscle actin (α-SMA), type Ⅰ and type Ⅲ collagen in gingival tissue and expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in gingival crevicular fluid under orthodontic force. METHODS: Seventy-four patients undergoing orthodontic treatment in Affiliated Stomatological Hospital of Nanchang University from April 2018 to April 2019 were enrolled, and randomly divided into three groups. Group A(n=24) received the treatment under 0 g of orthodontic force, group B (n=25) under 75 g of orthodontic force, and group C(n=25) under 150 g of orthodontic force. At the baseline and 4th week of treatment, the expression levels of α-SMA, type I collagen and type Ⅲ collagen in gingival tissues were detected by immunohistochemical staining. At the baseline, the 2nd, and 4th week of treatment, the expression levels of MMP-2 and TIMP-2 in gingival crevicular fluid were detected by enzyme-linked immunosorbent assay. Then the correlation between different orthodontic force and levels of α-SMA, type Ⅰ collagen, type Ⅲ collagen, MMP-2 and TIMP-2 was analyzed using Spearman correlation analysis. Statistical analysis was completed by SPSS 19.0 software package. RESULTS: At the 2nd and 4th week of treatment, the expression levels of MMP-2 and TIMP-2 in gingival crevicular fluid among three groups were the lowest in group A, followed by group B and group C(P<0.05). At the 4th week of treatment, the levels of α-SMA, type Ⅰ and type Ⅲ collagen in gingival tissues among three groups were the lowest in group A, followed by group B and group C(P<0.05). The orthodontic force was positively correlated with expression levels of α-SMA, type Ⅰ collagen, type Ⅲ collagen, MMP-2 and TIMP-2(P<0.05). CONCLUSIONS: The expression levels of MMP-2 and TIMP-2 in gingival crevicular fluid and myofibroblast are related to the changes of orthodontic force, which may play an important role in the reconstruction of periodontal tissue during orthodontic treatment.


Assuntos
Metaloproteinase 2 da Matriz , Inibidor Tecidual de Metaloproteinase-2 , Actinas , Colágeno Tipo III , Líquido do Sulco Gengival , Humanos , Metaloproteinase 8 da Matriz , Inibidor Tecidual de Metaloproteinase-1
20.
Front Cell Dev Biol ; 9: 722960, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646824

RESUMO

One contributor to the high mortality of osteosarcoma is its reduced sensitivity to chemotherapy, but the mechanism involved is unclear. Improving the sensitivity of osteosarcoma to chemotherapy is urgently needed to improve patient survival. We found that chemotherapy triggered apoptosis of human osteosarcoma cells in vitro and in vivo; this was accompanied by increased Sestrin2 expression. Importantly, autophagy was also enhanced with increased Sestrin2 expression. Based on this observation, we explored the potential role of Sestrin2 in autophagy of osteosarcoma. We found that Sestrin2 inhibited osteosarcoma cell apoptosis by promoting autophagy via inhibition of endoplasmic reticulum stress, and this process is closely related to the PERK-eIF2α-CHOP pathway. In addition, our study showed that low Sestrin2 expression can effectively reduce autophagy of human osteosarcoma cells after chemotherapy, increase p-mTOR expression, decrease Bcl-2 expression, promote osteosarcoma cell apoptosis, and slow down tumour progression in NU/NU mice. Sestrin2 activates autophagy by inhibiting mTOR via the PERK-eIF2α-CHOP pathway and inhibits apoptosis via Bcl-2. Therefore, our results explain one underlying mechanism of increasing the sensitivity of osteosarcoma to chemotherapy and suggest that Sestrin2 is a promising gene target.

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