RESUMO
The prevalent π-π interactions in 2D covalent organic frameworks (COFs) impart a certain flexibility to the structures, making the stacking of COF layers susceptible to external stimuli and introducing some structural disorder. Recent research indicates that the flexibility between COF layers and the associated disorder significantly influence their selective adsorption performance toward gas molecules. However, the adsorption process in a solution environment is more complex compared to gas-phase adsorption, involving interactions between adsorbents and adsorbates, as well as the solvation effects of flexible 2D COFs. Therefore, the inherent flexibility and disorder in 2D COFs under solution conditions and their impact on the adsorption performance of metal ions have not been observed yet. Herein, the synthesis of a novel carboxyl-functionalized COF featuring stable ß-ketoenamine and benzimidazole linkages, named DMTP-COOH, is presented. DMTP-COOH exhibits excellent selective adsorption capability for uranium, with significantly different adsorption capacities observed after treatment with different solvents. This notable difference in adsorption capacity is observed under varying pH, concentration, time, and even in the presence of multiple competing ions. This work represents the first observation of the significant impact of solvent soaking treatment on the selective adsorption performance of COFs for uranium under liquid conditions.
RESUMO
Intervertebral disc (IVD) degeneration (IVDD) is usually accompanied by nucleus pulposus (NP) fibrosis and pathologic angiogenesis, which are possibly associated with macrophage infiltration. Previous research indicates a destructive role of macrophages and the protective effect of inhibiting heat shock protein 90 (HSP90) in IVDD. Herein, the effects of inhibiting HSP90 on NP fibrosis and pathologic angiogenesis induced by macrophages were investigated further. Single-cell RNA-sequencing analysis was used to classify fibrotic NP cell (NPC) clusters and healthy NPC clusters in human NP tissues. The fibrotic NPC clusters were possibly associated with angiogenesis-related biological processes. Immunostaining showed the spatial association between blood vessel ingrowth and macrophage infiltration, as well as elevated levels of cell migration-inducing protein (CEMIP) and vascular endothelial growth factor A in severely degenerated human IVD tissues. Particularly, HSP90 inhibitor tanespimycin (17-AAG) ameliorated macrophage-induced fibrotic phenotype of NPCs via inhibiting CEMIP. M2, but not M1, macrophages promoted the pro-angiogenic ability of endothelial cells, which was attenuated by 17-AAG or HSP90 siRNA. Reversing the fibrotic phenotype of NPCs by Cemip siRNA also mitigated the pro-angiogenic effects of M2-conditioned medium-treated NPCs. Moreover, the murine IVDD model supported the 17-AAG-induced amelioration of NP fibrosis and endothelial cell invasion in IVD tissues. In conclusion, inhibiting HSP90 attenuated two interrelated pathologic processes, NP fibrosis and pathologic angiogenesis, induced by macrophages via down-regulating CEMIP.
Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Camundongos , Animais , Núcleo Pulposo/metabolismo , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais/metabolismo , Movimento Celular , Proteínas de Choque Térmico , Neovascularização Patológica/patologia , Macrófagos/metabolismo , Fibrose , RNA Interferente Pequeno/metabolismoRESUMO
Stitching interferometry is an essential technique for the non-contact, high-precision measurement of large apertures or complex optical surfaces. However, the accuracy of full-aperture surface reconstruction is significantly compromised by subaperture positioning and systematic errors. To address this challenge, this study introduces a novel stitching interferometry method utilizing alternating calibration of positioning and systematic errors (SIAC). This method calibrates one type of error while maintaining the other constant, and alternates between these processes to effectively decouple the two errors, facilitating accurate phase stitching. Within this calibration framework, an iterative weighted phase stitching model employing vertical projection for estimating overlapping areas was developed to calibrate positioning errors. Additionally, the rotation measurements of a single subaperture, in conjunction with a global fitting approach, were employed to correct reference errors. Numerical simulations have confirmed the efficacy of SIAC in calibrating these errors. Moreover, experimental measurements were performed on both a plane mirror and gullwing aspheres, with the resulting stitched full-aperture phase distributions and cross-testing outcomes affirming the method's accuracy and practicality. This research provides a novel solution for stitching interferometry, enhancing the precision of optical surface measurements.
RESUMO
The Xpert MTB/RIF test (Xpert) can help in the accurate screening of tuberculosis, however, its widespread use is limited by its high cost and lack of accessibility. Pooling of sputum samples for testing is a strategy to cut expenses and enhance population coverage but may result in a decrease in detection sensitivity due to the dilution of Mycobacterium tuberculosis (Mtb) by sample mixing. We investigated how the mixing ratio affected the detection performance of Xpert. We used frozen sputum samples that had been kept after individual Xpert assays of the sputa from Mtb-confirmed TB patients and non-TB patients. Our results showed that the overall sensitivity of the Xpert pooling assay remained higher than 80% when the mixing ratio was between 1/2 and 1/8. When the mixing ratio was raised to 1/16, the positive detection rate fell to 69.0%. For patients with either a high sputum Mtb smear score ≥ 2+, a time-to-positive culture ≤ 10 days, or an Xpert test indicating a high or medium abundance of bacteria, the pooling assay positivity rates were 93.3%, 96.8%, and 100% respectively, even at a 1/16 mixing ratio. For participants with cavities and cough, the pooling assay positivity rates were 86.2% and 90.0% at a 1/8 ratio, higher than for those without these signs. Our results show that the Xpert pooled assay has a high overall sensitivity, especially for highly infectious patients. This pooling strategy with lower reagent and labor costs could support TB screening in communities with limited resources, thereby facilitating reductions in the community transmission and incidence of TB worldwide.
Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Escarro , Tosse , BioensaioRESUMO
Morphological changes in the hippocampal, thalamic, and amygdala subfields have been suggested to form part of the pathophysiology of major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented in-depth examinations at the subfield level, precluding a fine-grained understanding of these subfields and their involvement in MDD pathophysiology. We uniquely employed ultra-high field MRI at 7.0 Tesla to map hippocampal, thalamic, and amygdala subfields in MDD. Fifty-six MDD patients and 14 healthy controls (HCs) were enrolled in the final analysis. FreeSurfer protocols were used to segment hippocampal, thalamic, and amygdala subfields. Bayesian analysis was then implemented to assess differences between groups and relations with clinical features. While no effect was found for MDD diagnosis (i.e., case-control comparison), clinical characteristics of MDD patients were associated with subfield volumes of the hippocampus, thalamus, and amygdala. Specifically, the severity of depressive symptoms, insomnia, and childhood trauma in MDD patients related to lower thalamic subfield volumes. In addition, MDD patients with typical MDD versus those with atypical MDD showed lower hippocampal, thalamic, and amygdala subfield volumes. MDD patients with recurrent MDD versus those with first-episode MDD also showed lower thalamic subfield volumes. These findings allow uniquely fine-grained insights into hippocampal, thalamic, and amygdala subfield morphology in MDD, linking some of them to the clinical manifestation of MDD.
RESUMO
The compatibility of crystallinity, stability, and functionality in covalent organic frameworks (COFs) is challenging but significant in reticular chemistry and materials science. Herein, it is presented for the first time a strategy to synthesize directly amino-functionalized COF with stable benzodiimidazole linkage by regioselective one-step cyclization and aromatization. Bandrowski's base with two types of amino groups is used as a unique monomer, providing not only construction sites for the material framework through specific region-selective reaction, but also amino active sites for functionality, which is usually difficult to achieve directly in COF synthesis because amino groups are the participants in COF bonding. In addition, the aromatic benzodiimidazole rings and the large conjugated system of the product effectively improve the crystallinity and stability, so that the as-prepared BBCOF remains unchanged in both acid and base solutions, which is obviously better than the conventional imine-linked COF. Impressively, the significantly enhanced conjugation degree by the benzodiimidazole structure also endows BBCOF with an efficient photocatalytic reduction of uranyl ion, with removal rate as high as 96.6% in single-ion system and 95% in multi-ion system. This study is of great importance to the design and synthesis of functional COFs with a commendable trade-off among crystallinity, stability, and functionality.
RESUMO
Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.
Assuntos
COVID-19 , Doenças Transmissíveis , Distúrbios do Início e da Manutenção do Sono , Gravidez , Feminino , Humanos , Idoso , COVID-19/epidemiologia , Pandemias , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Prevalência , Depressão/epidemiologia , Depressão/etiologia , SARS-CoV-2 , Ansiedade/epidemiologia , Ansiedade/etiologia , Fatores de Risco , Doenças Transmissíveis/epidemiologiaRESUMO
PURPOSE: Intertrochanteric femoral fractures (IFF) are one of the most common traumatic conditions, but there are no established treatment methods for this condition due to implant failure and re-operation rates. The proximal femoral bionic nail (PFBN), which is a new design of the cephalomedullary nail, was developed by our team. The objective of this study was to assess the clinical and radiographic outcomes of PFBN in patients with unstable IFF. METHODS: From October 2020 to August 2021, 12 patients diagnosed with unstable IFF (31-A2, 3) were treated with PFBN at the Third Hospital of Hebei Medical University. We evaluated the clinical therapeutic effects of this treatment by measuring peri-operative indicators and post-operative complications. Clinical outcomes, specific radiographic parameters, and post-operative complications were collected and analyzed within the first post-operative year. RESULTS: The average age of the patients was 72.4 ± 16.1 years (five males and seven females). The mean operation time was 90.4 ± 16.0 min, whereas the operation time of 31-A2 fractures (83.1 ± 12.2 min) was shorter than that of 31-A3 fractures (105.0 ± 12.9 min) (p < 0.05). The blood loss was 175 ml (range: 50 to 500 ml), and the length of hospitalization was 10.0 ± 1.9 days. The prognosis evaluation was assessed at three, six and 12 months after the operation; for these time points, the Harris hip scores were 69.6 ± 4.1, 77.8 ± 3.8, and 82.6 ± 4.6, respectively, and the Parker-Palmer scores were 5.3 (5.0, 7.0), 6.3 (5.3, 7.0), and 7.8 (7.0, 8.0), respectively. CONCLUSION: PFBN has shown advantages in the treatment of unstable IFF (particularly in geriatric patients) and possesses both stability and safety. This innovative method may provide a new option for treating unstable IFFs.
Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Quadril , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Fixação Intramedular de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/métodos , Pinos Ortopédicos , Biônica , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Fixação Interna de Fraturas/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Fraturas do Fêmur/cirurgiaRESUMO
(1) Annexins are proteins that bind phospholipids and calcium ions in cell membranes and mediate signal transduction between Ca2+ and cell membranes. They play key roles in plant immunity. (2) In this study, virus mediated gene silencing and the heterologous overexpression of TaAnn12 in Arabidopsis thaliana Col-0 trials were used to determine whether the wheat annexin TaAnn12 plays a positive role in plant disease resistance. (3) During the incompatible interaction between wheat cv. Suwon 11 and the Puccinia striiformis f. sp. tritici (Pst) race CYR23, the expression of TaAnn12 was significantly upregulated at 24 h post inoculation (hpi). Silencing TaAnn12 in wheat enhanced the susceptibility to Pst. The salicylic acid hormone contents in the TaAnn12-silenced plants were significantly reduced. The overexpression of TaAnn12 in A. thaliana significantly increased resistance to Pseudomonas syringae pv. tomato DC3000, and the symptoms of the wild-type plants were more serious than those of the transgenic plants; the amounts of bacteria were significantly lower than those in the control group, the accumulation of Reactive Oxygen Species (ROS)and callose deposition increased, and the expression of resistance-related genes (AtPR1, AtPR2, and AtPR5) significantly increased. (4) Our results suggest that wheat TaAnn12 resisted the invasion of pathogens by inducing the production and accumulation of ROS and callose.
Assuntos
Arabidopsis , Basidiomycota , Resistência à Doença , Espécies Reativas de Oxigênio/metabolismo , Triticum/microbiologia , Anexinas/metabolismo , Regulação da Expressão Gênica de Plantas , Arabidopsis/metabolismo , Doenças das Plantas/microbiologia , Basidiomycota/metabolismoRESUMO
Intervertebral disc (IVD) degeneration (IVDD) is the most common spinal disorder, which can lead to the symptoms of neck pain or low back pain. In healthy mature IVD tissues, extracellular matrix (ECM) complex possesses favorable biochemical and biomechanical properties, withstanding compression and torsion forces. IVD cells and ECM associate with each other to form a coordinated functional system. IVD cells are the main producers of ECM components, while ECM could modulate the viability and phenotype of IVD cells via direct interactions or indirect regulations. However, with the process of IVDD and ageing, ECM of IVD undergoes content loss and structure degeneration. Moreover, the accumulation of catabolic products may further deteriorate the IVD microenvironment. A better understanding of the physiology and the pathology of ECM within the IVD provides new insight into potential IVD regeneration strategies. Natural ECM components, functional motifs, or mimetic peptides are widely used in IVD repair by not only restoring structural support but also regulating cell fate and tissue microenvironment. Herein, we reviewed recent advances in the involvement of ECM in IVD health and disease, with an emphasis on ECM composition and organization, cell-matrix interactions, pathological ECM degradation, and promising matrix-based biomaterials for IVD regeneration.
Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Dor Lombar , Materiais Biocompatíveis , Matriz Extracelular/metabolismo , Humanos , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Dor Lombar/patologiaRESUMO
The cornea is one of the major refractive eye components and could be easily injured. An ineffective healing of corneal stromal wound may cause fibrosis and even loss of vision. Therefore, it is pivotal to prevent corneal fibrosis after injury. In this study, a poly (ε-caprolactone) (PCL) microfibrous scaffold infused with rat tail collagen type I was fabricated to obtain a 3D composite material. Physical and biological properties of PCL/collagen scaffold were evaluated, the effect of PCL/collagen scaffold on the proliferation and differentiation of limbal stromal stem cells (LSSCs) were detected in vitro, the differentiation of keratocytes as well as the expression and arrangement of extracellular matrix (ECM) influenced by PCL/collagen scaffold were investigated in vivo. RNA-sequencing on normal and injured corneas was carried out to find out the differential enriched pathways and gene expression. We discovered that the PCL/collagen scaffold simulated the stromal structure with properties that were most similar to the native cornea, the PCL/collagen scaffold exhibited good mechanical and biological properties. We also observed that the PCL/collagen scaffold reduced keratocyte differentiation. Injured corneas treated with PCL/collagen scaffold exhibited more regular collagen distribution and less fibroblasts and myofibroblasts distribution. By RNA-sequencing, we observed that in injured group, ECM-related pathway was enriched and several ECM-related genes were up-regulated. This study provides evidence that application of PCL/collagen scaffold could be a new therapeutic strategy for corneal injury.
Assuntos
Lesões da Córnea , Substância Própria , Animais , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Córnea/metabolismo , Lesões da Córnea/metabolismo , Substância Própria/metabolismo , Fibrose , RNA/metabolismo , Ratos , Cauda/metabolismoRESUMO
BACKGROUND: Recently, an animal model for depression has shown that ketamine, an N-methyl- d-aspartate receptor (NMDAR) antagonist, elicits a rapid-acting antidepressant effect by blocking NMDAR-dependent bursting in the lateral habenula (Hb). However, evidence from human studies remains scarce. METHODS: This study explored the changes of resting-state functional connectivity (FC) of the Hb in responders and nonresponders who was diagnosed with unipolar or bipolar depression before and after ketamine treatment. The response was defined as a ≥50% reduction in the total MADRS score at Day 13 (24 h following the sixth infusion) in comparison with the baseline score. Correlation analyses were performed to identify an association between symptom improvement and the signals of the significantly different brain regions detected in the above imaging analysis. RESULTS: In the post-hoc region-of-interest analysis, an enhanced baseline FC between Hb and several hubs of the default mode network (including angulate cortex, precuneus, medial prefrontal cortex, and middle temporal cortex) was observed in responders (≥50% decrease in the Montgomery-Asberg Scale at 2 weeks) compared with nonresponders. CONCLUSIONS: These pilot findings may suggest a potential neural mechanism by which ketamine exerts its robust antidepressant efficacy via downregulation of aberrant habenular FC with parts of the default mode network.
Assuntos
Habenula , Ketamina , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Córtex Cerebral , Rede de Modo Padrão , Humanos , Ketamina/farmacologia , Ketamina/uso terapêutico , Imageamento por Ressonância Magnética , Receptores de N-Metil-D-AspartatoRESUMO
Inhalation exposure to polycyclic aromatic hydrocarbons (PAHs) from indoor solid fuel combustion poses a high health risk, and PAHs bound to particles with smaller sizes (e.g., PM1.0, aerodynamic diameter ≤ 1.0 µm) should be of particular concern since they can penetrate deep into pulmonary alveoli. However, PAHs bound to PM1.0 was less studied compared with PAHs in total suspended particles or PM2.5. In this study, multiple provincial field measurements were conducted to investigate 28 PAHs bound to PM1.0 in rural Chinese homes. Daily averaged PM1.0-PAH28 concentrations ranged from 27 ng/m3 to 3795 ng/m3 (median: 233 ng/m3) and from 10 ng/m3 to 2978 ng/m3 (median: 87 ng/m3) in indoor and outdoor air, respectively. Higher concentrations were found in northern China in winter due to increased solid fuels consumption for space heating. The ambient pollution was lower during the non-heating season in Eastern China, where clean energy was preferred. Highly toxic congeners were more abundant in indoor air compared with outdoor air. The results of source apportionment revealed that solid fuel combustion was the primary contributor to rural household PM1.0-PAHs, but other sources such as vehicles cannot be overlooked. The transition to cleaner energy can reduce the indoor PM1.0-PAH28 and BaPeq-28 concentrations by 87% and 98%, respectively, and more efficient reduction was observed for highly toxic congeners. The estimated Incremental Lifetime Cancer Risk (ILCR) based on PM1.0-PAH28 ranged from 4.6 × 10-5 to 3.4 × 10-2, far exceeding the acceptable level of 10-6. Over 60% of the ILCR could be attributed to inhalation exposure during childhood and adolescence.
Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Adolescente , Humanos , Acidentes , Povo Asiático , Exposição por Inalação/efeitos adversos , ChinaRESUMO
The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.
Assuntos
Anti-Infecciosos/química , Desenho de Fármacos , Fototerapia/métodos , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Biofilmes/efeitos da radiação , Corantes/química , Corantes/farmacologia , Equipamentos e Provisões/microbiologia , Equipamentos e Provisões/virologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Oftalmopatias/tratamento farmacológico , Oftalmopatias/patologia , Fungos/efeitos dos fármacos , Grafite/química , Luz , Nanopartículas/química , Nanopartículas/toxicidade , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Teoria Quântica , Espécies Reativas de Oxigênio/metabolismo , Vírus/efeitos dos fármacosRESUMO
The endogenous repair failure of degenerated intervertebral disk (IVD) is highly related to the exhaustion of nucleus pulposus stem cells (NPSCs). Excessive oxidative stress could induce apoptosis and senescence of NPSCs, thus, declining the quantity and quality of NPSCs. Heat shock protein 70 (HSP70) is a family of cytoprotective and antioxidative proteins. However, there is no report on the protective effects of HSP70 on oxidative stress-induced NPSC impairments and underlying mechanisms. In the present study, we treated NPSCs with tert-butyl hydroperoxide (t-BHP) in vitro to simulate an oxidative stress condition. HSP70 inducer TRC051384 was used to evaluate the cytoprotective effects of HSP70. The results suggested that HSP70 impeded t-BHP-mediated cell viability loss and protected the ultrastructure of NPSCs. Moreover, t-BHP could induce mitochondrial apoptosis and p53/p21-mediated senescence of NPSCs, both of which were significantly inhibited in HSP70 activation groups. Excessive oxidative stress and mitochondrial dysfunction reinforced each other and contributed to the cellular damage processes. HSP70 decreased reactive oxygen species (ROS) production, rescued mitochondrial membrane potential (MMP) collapse, and blocked ATP depletion. Finally, our data showed that HSP70 downregulated the JNK/c-Jun pathway. Taken together, activation of HSP70 could protect against t-BHP-induced NPSC apoptosis and senescence, thus, improving the quantity and quality of NPSCs. Therefore, HSP70 may be a promising therapeutic target for IVD degeneration.
Assuntos
Apoptose/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , MAP Quinase Quinase 4/metabolismo , Núcleo Pulposo/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/metabolismo , terc-Butil Hidroperóxido/farmacologia , Células Cultivadas , HumanosRESUMO
Suicide is a tremendous threat to global public health, and a large number of people who committed suicide suffered the pain of mental diseases, especially major depressive disorder (MDD). Previous study showed that ketamine could reduce suicidal ideation (SI), potentially by improving the impaired working memory (WM). The objective of current study was to illuminate the relationship between WM and SI in MDD with repeated ketamine treatment. MDD patients with SI (n = 59) and without SI (n = 37) completed six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days (Day 1, 3, 5, 8, 10 and 12). The severity of depressive symptoms, SI and WM were assessed at baseline, day 13 and day 26. We found that WM was significantly improved after 6 ketamine infusions (F = 161.284, p = 0.009) in a linear mixed model. Correlation analysis showed that the improvement of depressive symptom was significantly associated with WM at baseline (r = - 0.265, p = 0.042) and the reduction in SSI-part I was related to the change of WM (r = 0.276, p = 0.034) in the MDD patients with SI. Furthermore, Logistic regression analysis showed that improvement in WM might predict the anti-SI response of ketamine. Our findings suggest that the improvement of working memory may partly account for the anti-SI effect of ketamine, and intervention of improving working memory function may be capable of reducing suicidal ideation.
Assuntos
Antidepressivos/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Memória de Curto Prazo/efeitos dos fármacos , Ideação Suicida , Adulto , Antidepressivos/administração & dosagem , Disfunção Cognitiva/etiologia , Transtorno Depressivo Maior/complicações , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Ketamina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND: Although lower temperature (< 45 °C) photothermal therapy (LPTT) have attracted enormous attention in cancer therapy, the therapeutic effect is still unsatisfying when applying LPTT alone. Therefore, combining with other therapies is urgently needed to improve the therapeutic effect of LPTT. Recently reported oxygen-irrelevant free radicals based thermodynamic therapy (TDT) exhibit promising potential for hypoxic tumor treatment. However, overexpression of glutathione (GSH) in cancer cells would potently scavenge the free radicals before their arrival to the specific site and dramatically diminish the therapeutic efficacy. METHODS AND RESULTS: In this work, a core-shell nanoplatform with an appropriate size composed of arginine-glycine-aspartate (RGD) functioned polydopamine (PDA) as a shell and a triphenylphosphonium (TPP) modified hollow mesoporous manganese dioxide (H-mMnO2) as a core was designed and fabricated for the first time. This nanostructure endows a size-controllable hollow cavity mMnO2 and thickness-tunable PDA layers, which effectively prevented the pre-matured release of encapsulated azo initiator 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI) and revealed pH/NIR dual-responsive release performance. With the mitochondria-targeting ability of TPP, the smart nanocomposites (AIBI@H-mMnO2-TPP@PDA-RGD, AHTPR) could efficiently induce mitochondrial associated apoptosis in cancer cells at relatively low temperatures (< 45 °C) via selectively releasing oxygen-irrelevant free radicals in mitochondria and facilitating the depletion of intracellular GSH, exhibiting the advantages of mitochondria-targeted LPTT/TDT. More importantly, remarkable inhibition of tumor growth was observed in a subcutaneous xenograft model of osteosarcoma (OS) with negligible side effects. CONCLUSIONS: The synergistic therapy efficacy was confirmed by effectively inducing cancer cell death in vitro and completely eradicating the tumors in vivo. Additionally, the excellent biosafety and biocompatibility of the nanoplatforms were confirmed both in vitro and in vivo. Taken together, the current study provides a novel paradigm toward oxygen-independent free-radical-based cancer therapy, especially for the treatment of hypoxic solid tumors.
Assuntos
Radicais Livres , Nanopartículas Metálicas/química , Mitocôndrias , Sistemas de Liberação de Fármacos por Nanopartículas , Terapia Fototérmica , Animais , Compostos Azo/química , Linhagem Celular Tumoral , Temperatura Baixa , Feminino , Radicais Livres/análise , Radicais Livres/metabolismo , Humanos , Imidazóis/química , Compostos de Manganês/química , Camundongos , Camundongos Nus , Mitocôndrias/química , Mitocôndrias/metabolismo , Óxidos/químicaRESUMO
BACKGROUND: Despite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. Amplification of intracellular oxidative stress is considered as an effective strategy to induce cancer cell death. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy. METHODS AND RESULTS: A novel nanocomposite, composed of folic acid (FA) modified mesoporous silica-coated gold nanostar (GNS@MSNs-FA) and traditional Chinese medicine lycorine (Ly), was rationally designed and developed. Under near-infrared (NIR) irradiation, the obtained GNS@MSNs-FA/Ly could promote a high level of ROS production via inducing mitochondrial dysfunction and potent endoplasmic reticulum (ER) stress. Moreover, glutathione (GSH) depletion during ER stress could reduce ROS scavenging and further enable efficient amplification of intracellular oxidative stress. Both in vitro and in vivo studies demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation exhibited excellent antitumor efficacy without noticeable toxicity in MNNG/HOS tumor-bearing mice. CONCLUSION: All these results demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation could dramatically amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without obvious systemic toxicity. Taken together, this promising strategy provides a new avenue for the effective cancer synergetic therapy and future clinical translation.
Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Ouro/química , Nanocompostos/química , Neoplasias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fenantridinas/farmacologia , Animais , Materiais Biocompatíveis , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Estresse do Retículo Endoplasmático , Ácido Fólico , Humanos , Camundongos , Microscopia de Fluorescência , Mitocôndrias , Nanocompostos/uso terapêutico , Neoplasias/patologia , Osteossarcoma , Espécies Reativas de Oxigênio , Dióxido de SilícioRESUMO
BACKGROUND: Several studies have demonstrated a relationship between the posterior tibial slope (PTS) and meniscal tears in adults. However, little is known about the association between the PTS of the adolescents and medial meniscal tears (MMT). The purpose of this study was to evaluate the association between the PTS and MMT in adolescents, and to determine the optimal cut-off values of PTS for discriminating between the MMT and the control groups. METHODS: Between January 2018 and January 2020, a retrospective case-control study was performed. In this study, isolated MMT adolescent patients with no ligamentous injuries were matched by age and sex to a control group of radiologically normal images. The PTS was defined as the angle between the perpendicular line to proximal tibial cortex (PTC) and the tangent line along the tibial plateau. Then, both the medial posterior tibial slope (MPTS) and lateral posterior tibial slope (LPTS) were measured by plain radiographs on the lateral views. In addition, the optimal cut-off values of PTS were determined by the receiver operating characteristic (ROC) curve analysis. RESULTS: A total of seventy-two patients who met the inclusion criteria were enrolled in the final analysis (36 patients with isolated MMT, 36 controls). The MPTS was greater in the knees with isolated MMT (10.7° ± 2.1°) than that of the control group (8.8° ± 1.7°), showing significant difference (P<0.001). However, there was no significant difference regarding the LPTS between the isolated MMT and controls (11.5 ± 3.4 vs 10.9 ± 2.6, p>0.05). In the ROC curve analysis, the calculated cutoff value of the MPTS discriminating between the groups was 10.3°, with a sensitivity of 73.3% and specificity of 78.9%. CONCLUSIONS: This study demonstrated that steep MPTS is associated with MMT, and MPTS≥10.3° was identified to be a risk factor for MMT in adolescents.
Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho , Adolescente , Adulto , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética , Meniscos Tibiais/diagnóstico por imagem , Estudos Retrospectivos , Tíbia/diagnóstico por imagemRESUMO
PURPOSE: The purpose of this study was to evaluate the long-term clinical and radiographic outcomes of partial patellectomy (PP) in patients with patella comminuted distal pole fractures. METHODS: Seventeen patients who were diagnosed with patella comminuted distal pole fractures and underwent PP procedures were retrospectively included between January 1995 and January 2005. We collected patient demographics and data on the mechanism of injury, time to surgery, fracture type, follow-up time, and post-operative complications (infection, patellofemoral arthritis, and stiffness). At the final follow-up, functional outcome was evaluated by the range of motion (ROM) and the Bostman Scoring System. Quadriceps strength was evaluated by using an isokinetic dynamometer to measure peak torque, and patellar height was evaluated by the Insall-Salvati (IS) ratio in lateral knee radiographs. The average follow-up period was 14.6 years (range, 11-19 years). RESULTS: We analyzed 17 patients (AO/OTA 34-A1), with an average age of 59.8 years (range, 43-76 years). According to the Bostman grading scales, final functional outcomes were excellent in 11 (64.7%) and good in six (35.3%) patients. All patients had full knee extension, and the average ROM was 125.1° (range, 121.4-129.3°). The average peak torque of the injured knee was 103.2 ± 9.7 Nm, and that of the uninjured opposite side was 108.3 ± 7.6 Nm, with no significant difference (p > 0.05). Furthermore, no postoperative complications, such as infection, posttraumatic osteoarthritis, or stiffness, were observed. Compared to the uninjured knee, the IS ratio of the injured knee was 0.76 ± 0.13, indicating that the patellar height was decreased, which meant patella baja. CONCLUSIONS: The PP procedure for patella comminuted distal pole fractures is a safe, simple, and reliable technique that can provide good long-term clinical outcomes even with decreased patellar height and could be a satisfactory alternative treatment option when anatomical reduction is difficult.