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1.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39000460

RESUMO

Aberrant aggregation of misfolded alpha-synuclein (α-syn), a major pathological hallmark of related neurodegenerative diseases such as Parkinson's disease (PD), can translocate between cells. Ubiquitin-like 3 (UBL3) is a membrane-anchored ubiquitin-fold protein and post-translational modifier. UBL3 promotes protein sorting into small extracellular vesicles (sEVs) and thereby mediates intercellular communication. Our recent studies have shown that α-syn interacts with UBL3 and that this interaction is downregulated after silencing microsomal glutathione S-transferase 3 (MGST3). However, how MGST3 regulates the interaction of α-syn and UBL3 remains unclear. In the present study, we further explored this by overexpressing MGST3. In the split Gaussia luciferase complementation assay, we found that the interaction between α-syn and UBL3 was upregulated by MGST3. While Western blot and RT-qPCR analyses showed that silencing or overexpression of MGST3 did not significantly alter the expression of α-syn and UBL3, the immunocytochemical staining analysis indicated that MGST3 increased the co-localization of α-syn and UBL3. We suggested roles for the anti-oxidative stress function of MGST3 and found that the effect of MGST3 overexpression on the interaction between α-syn with UBL3 was significantly rescued under excess oxidative stress and promoted intracellular α-syn to extracellular transport. In conclusion, our results demonstrate that MGST3 upregulates the interaction between α-syn with UBL3 and promotes the interaction to translocate intracellular α-syn to the extracellular. Overall, our findings provide new insights and ideas for promoting the modulation of UBL3 as a therapeutic agent for the treatment of synucleinopathy-associated neurodegenerative diseases.


Assuntos
Glutationa Transferase , Estresse Oxidativo , Ubiquitinas , alfa-Sinucleína , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Humanos , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Ubiquitinas/metabolismo , Ubiquitinas/genética , Regulação para Cima , Transporte Proteico , Doença de Parkinson/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/patologia , Ligação Proteica
2.
BMC Endocr Disord ; 24(1): 87, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867258

RESUMO

BACKGROUND: Anaplastic thyroid carcinoma(ATC) is a rare pathological type of thyroid malignancy. Primary squamous cell carcinoma of thyroid(PSCCT) is now considered as a subtype of ATC, hereinafter referred to as ATC-SCC subtype. ATC-SCC subtype combined with follicular thyroid carcinoma is exceedingly rare, with fewer cases reported. The ATC-SCC subtype is a highly invasive tumor with a poor prognosis for patients after metastasis occurs, and current treatment of this type of tumor is tricky. CASE PRESENTATION: A 68-year-old female patient presented with a gradually growing swelling of right cervical region. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of ATC-SCC subtype with follicular thyroid carcinoma, and the metastasis squamous cell carcinoma of the right cervical lymph nodes originates from ATC-SCC subtype. The patient received chemoradiotherapy postoperative. However, the residual cervical lymph nodes metastasis with squamous cell carcinoma still infiltrated surrounding structures in the neck extensively after palliative resection. The patient died 7 months after surgery. CONCLUSION: Our case highlights that cervical lymph node metastasis may be a significant factor in the poor prognosis of ATC-SCC subtype. This malignancy should be detected and treated early.


Assuntos
Adenocarcinoma Folicular , Metástase Linfática , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Feminino , Idoso , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/secundário , Carcinoma Anaplásico da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/diagnóstico , Carcinoma Anaplásico da Tireoide/terapia , Prognóstico , Evolução Fatal , Pescoço/patologia , Linfonodos/patologia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico
3.
Angew Chem Int Ed Engl ; 63(28): e202405372, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38659283

RESUMO

Rational modulation of surface reconstruction in the oxygen evolution reaction (OER) utilizing defect engineering to form efficient catalytic activity centers is a topical interest in the field of catalysis. The introduction of point defects has been demonstrated to be an effective strategy to regulate the electronic configuration of electrocatalysts, but the influence of more complex planar defects (e.g., twins and stacking faults), on their intrinsic activity is still not fully understood. This study harnesses ultrasonic cavitation for rapid and controlled introduction of different types of defects in the FeCoNi/FeAl2O4 hybrid coating, optimizing OER catalytic activity. Theoretical calculations and experiments demonstrate that the different defects optimize the coordination environment and facilitate the activation of surface reconstruction into true catalytic activity centers at lower potentials. Moreover, it demonstrates exceptional durability, maintaining stable oxygen production at a high current density of 300 mA cm-2 for over 120 hours. This work not only presents a novel pathway for designing advanced electrocatalysts but also deepens our understanding of defect-engineered catalytic mechanisms, showcasing the potential for rapid and efficient enhancement of electrocatalytic performance.

4.
Environ Pollut ; 346: 123564, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38367693

RESUMO

Histone modifications maintain genomic stability and orchestrate gene expression at the chromatin level. Benzo [a]pyrene (BaP) is the ubiquitous carcinogen widely spread in the environment, but the role and regulatory mechanism of histone modification in its toxic effects remain largely undefined. In this study, we found a dose-dependent reduction of histone H3 methylations at lysine4, lysine9, lysine27, lysine36 in HBE cells treated with BaP. We observed that inhibiting H3K27 and H3K36 methylation impaired cell proliferation, whereas the loss of H3K4, H3K9, H3K27, and H3K36 methylation led to increased genomic instability and delayed DNA repair. H3K36 mutation at both H3.1 and H3.3 exhibited the most significant impacts. In addition, we found that the expression of SET domain containing 2 (SETD2), the unique methyltransferase catalyzed H3K36me3, was downregulated by BaP dose-dependently in vitro and in vivo. Knockdown of SETD2 aggravated DNA damage of BaP exposure, which was consistent with the effects of H3K36 mutation. With the aid of chromatin immunoprecipitation (ChIP) -seq and RNA-seq, we found that H3K36me3 was responsible for transcriptional regulation of genes involved in pathways related to cell survival, lung cancer, metabolism and inflammation. The enhanced enrichment of H3K36me3 in genes (CYP1A1, ALDH1A3, ACOXL, WNT5A, WNT7A, RUNX2, IL1R2) was positively correlated with their expression levels, while the reduction of H3K36me3 distribution in genes (PPARGC1A, PDE4D, GAS1, RNF19A, KSR1) were in accordance with the downregulation of gene expression. Taken together, our findings emphasize the critical roles and mechanisms of histone lysine methylation in mediating cellular homeostasis during BaP exposure.


Assuntos
Benzo(a)pireno , Histonas , Humanos , Histonas/metabolismo , Benzo(a)pireno/toxicidade , Metilação , Instabilidade Genômica , Células Epiteliais/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
5.
Clin Biomech (Bristol, Avon) ; 113: 106206, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38401320

RESUMO

BACKGROUND: Kinematic analysis has been recommended to quantify the upper limb motor function after stroke. However, previous studies have rarely reported the kinematic data of the post-stroke patients with moderate to severe upper limb paresis due to the poor accomplishment of the complex tasks. METHODS: 27 post-stroke individuals and 20 non-disabled people participated in the study. The trunk and upper limb movements during the Hand-to-mouth task were captured by the motion capture system and upper extremity kinematic analysis software automatically. The subgroup analysis within stroke group were conducted layering by the Fugl-Meyer Assessment for Upper Extremity scores (severe: 16-31; moderate: 32-50). FINDINGS: The paretic upper limbs in the stroke group tended to use more trunk and shoulder compensatory strategies to offset the impact of spasticity and weakness compared with non-disabled controls. The less-affected limbs in the stroke group also showed abnormal kinematic data. There were significant differences between the kinematic metrics of severe and moderate subgroups. INTERPRETATION: The Hand-to-mouth task is a good and feasible option for kinematic analysis of these patients. It is essential to layer the severity of the paresis and put more emphasis on trunk movements in the future kinematic studies.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Fenômenos Biomecânicos , Extremidade Superior , Acidente Vascular Cerebral/complicações , Paresia/etiologia
6.
Transl Cancer Res ; 12(10): 2582-2595, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969391

RESUMO

Background: The aberrant expression of the classical tumor suppressor gene p16 is a frequent event in lung cancer mainly due to the hypermethylation of its 5'-cytosine-phosphate-guanine-3' island (Cgi). However, whether methylation happens in other regions and how p16 expression and function are affected are largely unknown. Methods: Clustered Regularly Interspaced Short Palindromic Repeats/dCas9 (CRISPR/dCas9) technology was used for methylation editing at specific site of p16. The effects of methylation editing were detected by 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS), transwell migration and wound healing tests. Chromatin immnoprecipitation-quantitative polymerase chain reaction (CHIP-qPCR) was performed to explore the impact of Cgi shore methylation on the binding abilities of transcription factors (TFs) including YY1, SP1, ZNF148 and OTX2 to p16 gene. A rescue experiment was performed to verify the regulatory effect of OTX2 on p16. The negative relationship between p16 expression and the methylation level of Cgi shore in non-promoter region was further verified with datasets from The Cancer Genome Atlas (TCGA) program and lung adenocarcinoma (LUAD) patients' samples. Results: The suppressive effect of p16 Cgi shore methylation on its expression was demonstrated in both HEK293 and A549 cells using CRISPR/dCas9-mediated specific site methylation editing. Methylation of the Cgi shore in the p16 non-promoter region significantly decreased its expression and promoted cell growth and migration. The ability of OTX2 bound to p16 was significantly reduced by 19.35% after methylation modification. Over-expression of OTX2 in A549 cells partly reversed the inhibitory effect of methylation on p16 expression by 19.04%. The verification results with TCGA and LUAD patients' samples supported that the p16 Cgi shore is a key methylation regulatory region. Conclusions: Our findings suggested that methylation of the Cgi shore in the p16 non-promoter region can hamper the transcriptional activity of OTX2, leading to a reduction in the expression of p16, which might contribute to the development of lung cancer.

7.
Zhongguo Zhen Jiu ; 43(9): 1081-5, 2023 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-37697886

RESUMO

Acupuncture and moxibustion has certain advantages in the treatment of post-stroke spastic paralysis,but the treatment methods and diagnosis and treatment ideas are complicated. This paper sortes out the representative contemporary acupuncture and moxibustion schools in the treatment of post-stroke spastic paralysis, analyzes their academic origins,summarizes and compares the theory,acupoint selection and technique characteristics of different schools in the diagnosis and treatment of this disease,so as to provide some references for guiding optimal treatment schemes selection in clinic.


Assuntos
Terapia por Acupuntura , Moxibustão , Acidente Vascular Cerebral , Humanos , Espasticidade Muscular/etiologia , Espasticidade Muscular/terapia , Instituições Acadêmicas , Pontos de Acupuntura , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia
8.
Foot Ankle Surg ; 29(3): 261-267, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36813592

RESUMO

BACKGROUND: This study aims to assess the mechanical and functional effects of the arthroscopic modified Broström procedure (AMBP) on patients with lateral ankle instability. METHODS: Eight patients with unilateral ankle instability treated with AMBP and eight healthy subjects were recruited. Healthy subjects, preoperative and one-year postoperative patients were assessed using outcome scales and the Star Excursion Balance Test (SEBT) for dynamic postural control. One-dimensional statistical parametric mapping was performed to compare ankle angle and muscle activation curve during stair descent. RESULTS: The patients with lateral ankle instability showed good clinical outcomes and increased posterior lateral reach during the SEBT after the AMBP (p = 0.046). The medial gastrocnemius activation after initial contact was reduced (p = 0.049), and the peroneal longus activation after initial contact was promoted (p = 0.014). CONCLUSION: The AMBP has functional effects of promoting dynamic postural control and peroneal longus activation within one year of follow-up, which can benefit patients with functional ankle instability. However, the medial gastrocnemius activation was unexpectedly reduced post operation.


Assuntos
Instabilidade Articular , Ligamentos Laterais do Tornozelo , Humanos , Tornozelo , Projetos Piloto , Articulação do Tornozelo/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia , Instabilidade Articular/cirurgia
9.
Arch Toxicol ; 97(2): 441-456, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36336710

RESUMO

Cisplatin is recommended as a first-line chemotherapeutic agent against advanced non-small cell lung cancer (NSCLC), but acquired resistance substantially limits its clinical efficacy. Recently, DNA methylation has been identified as an essential contributor to chemoresistance. However, the precise DNA methylation regulatory mechanism of cisplatin resistance remains unclear. Here, we found that nicotinamide nucleotide transhydrogenase (NNT) was silenced by DNA hypermethylation in cisplatin resistance A549 (A549/DDP) cells. Also, the DNA hypermethylation of NNT was positively correlated to poor prognosis in NSCLC patients. Overexpression of NNT in A549/DDP cells could reduce their cisplatin resistance, and also suppressed their tumor malignancy such as cell proliferation and clone formation. However, NNT enhanced sensitivity of A549/DDP cells to cisplatin had little to do with its function in mediating NADPH and ROS level, but was mainly because NNT could inhibit protective autophagy in A549/DDP cells. Further investigation revealed that NNT could decrease NAD+ level, thereby inactivate SIRT1 and block the autophagy pathway, while re-activation of SIRT1 through NAD+ precursor supplementation could antagonize this effect. In addition, targeted demethylation of NNT CpG island via CRISPR/dCas9-Tet1 system significantly reduced its DNA methylation level and inhibited the autophagy and cisplatin resistance in A549/DDP cells. Thus, our study found a novel chemoresistance target gene NNT, which played important roles in cisplatin resistance of lung cancer cells. Our findings also suggested that CRISPR-based DNA methylation editing of NNT could be a potential therapeutics method in cisplatin resistance of lung cancer.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , NADP Trans-Hidrogenases , Humanos , Células A549 , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Autofagia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Cisplatino/farmacologia , DNA , Metilação de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , NAD/metabolismo , NADP Trans-Hidrogenases/genética , NADP Trans-Hidrogenases/metabolismo , Sirtuína 1/metabolismo
10.
Chinese Journal of School Health ; (12): 946-950, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-976573

RESUMO

Abstract@#Flexibleis an important classification of flat foot. Flatfoot occurs due to a variety of reasons and causes the medial longitudinal arch to collapse or disappear. However, many children still do not develop a normal foot arch as the grow, and a failure to intervene in a timely manner will greatly harm a child s normal mobility development. Timely detection and intervention are the key to improve the prognosis. There is a lack of uniform quantitative criteria for the diagnosis of flexible flatfoot. Currently, the commonly used diagnostic methods include physical examination, foot printing, plantar pressure test and imaging examination. This article reviews the risk factors, diagnosis, prevention and treatment of Flexible Flatfoot.

11.
Toxicol Appl Pharmacol ; 449: 116109, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35688185

RESUMO

Airborne nano-scale particulate matter (nPM) exposure is a risk factor for neurological diseases. However, to date, there has been no comprehensive evaluation of ambient nPM's neurotoxicity. We examined the toxic effects of nPM on human neurons derived from induced pluripotent stem cells (iPSCs) at doses ranging from 0 to 200 µg/mL, and employed whole-genome RNA-sequencing in different dose groups to gain further insight into the neurotoxicity of ambient nPM. Our findings showed that nPM was absorbed by neurons, and induced a variety of toxic effects. The apical benchmark dose lower confidence bound (aBMDL) values of each effect endpoint were ranked as follows, in ascending order: mitochondrial membrane potential, neurite length, early apoptosis, cell viability. BMD analysis based on transcriptomic data revealed that the point of departure (PoD) of the 20 pathways with the lowest p-values (0.75 µg/mL), the top 20 upstream regulators (0.79 µg/mL) and the neurological diseases (0.77 µg/mL) could be appropriate for nPM neurotoxicity evaluation. The transcriptomic PoDs (tPoDs) were similar to apical PoDs (aPoDs) since their absolute fold differences were within 10-fold. Further analysis of the transcriptomic data revealed that nPM exposure could disturb the pathways related to ferroptosis, neurotransmitters, xenobiotic metabolism, etc., which might be critical in regulating nPM neurotoxicity. We also found that low-dose nPM induced cytokine signaling pathways, while high doses of nPM activated cell-cycle regulation and DNA repair pathways. Our results indicate that BMD modeling based on transcriptomic data could be useful in illustrating the neurotoxic mechanism, and also could be a promising method for evaluating the potential health risks of nPM.


Assuntos
Células-Tronco Pluripotentes Induzidas , Síndromes Neurotóxicas , Benchmarking , Humanos , Neurônios , Síndromes Neurotóxicas/genética , Material Particulado/toxicidade , Transcriptoma
12.
Gait Posture ; 96: 306-313, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35772346

RESUMO

BACKGROUND: Previous studies on the kinematics of patients with chronic ankle instability (CAI) that did not incorporate MRI and arthroscopic assessment could not differentiate between patients with CAI without osteochondral lesion of the talus (OLT) and patients with CAI and OLT and have thus presented contradictory results. RESEARCH QUESTION: This study aimed to investigate the kinematic and electromyographic differences between patients with and without OLT. METHODS: Sixteen subjects with CAI (eight without OLT and eight with OLT confirmed through MRI and arthroscopic assessment) and eight healthy subjects underwent gait analysis in a stair descent setting. The three groups' patient-reported outcomes; ankle joint range of motion in flexion, inversion and rotation; and muscle activation of the peroneus, tibialis anterior, and gastrocnemius during a gait cycle were analyzed and compared. A curve analysis, namely, one-dimensional statistical parametric mapping, was performed to compare the dynamic ankle kinematics and muscle activation curves over the entire normalized time series. RESULTS: The patients with and without OLT had no difference in patient-reported outcomes. The maximal ankle plantarflexion of the patients without OLT and the healthy subjects was significantly larger than that of patients with OLT (p = 0.005). The maximal ankle internal rotation of patients without OLT was significantly larger than that of patients with OLT (p = 0.048). The peroneal activation during 0-6% of the gait cycle of patients with OLT was reduced compared with the healthy subjects. SIGNIFICANCE: Patients with CAI and OLT and patients with CAI without OLT have no difference in patient-reported outcomes, but patients with OLT can be differentiated using the post-initial-contact peroneal activation deficit and the restriction of ankle plantarflexion and internal rotation during stair descent. These variables can be utilized to monitor the function of patients with CAI and their possibility of developing OLT.


Assuntos
Instabilidade Articular , Tálus , Tornozelo , Articulação do Tornozelo , Fenômenos Biomecânicos , Humanos , Projetos Piloto
13.
Knee Surg Sports Traumatol Arthrosc ; 30(11): 3888-3897, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35568754

RESUMO

PURPOSE: A biomechanical study, in which imaging modalities are used to strictly include patients with concurrent lateral ankle instability (LAI) and osteochondral lesions of the talus (OLT), is needed to demonstrate the static and dynamic ankle range of motion (ROM) restriction in these patients, and determine whether ankle ROM restriction can be corrected postoperatively. METHODS: Eight patients with concurrent LAI and OLT treated with the arthroscopic modified Broström procedure and microfracture were recruited from June 2019 to January 2020. Patients were assessed using outcome scales, static ankle ROM, and a stair descent gait analysis for dynamic ankle ROM, a day prior to surgery and one year postoperatively. Eight healthy subjects were assessed using the same modalities upon recruitment. Operative outcomes and variables during stair descent were documented and compared among the preoperative, postoperative, and healthy groups. A curve analysis, one-dimensional statistical parametric mapping, was performed to compare the dynamic ankle kinematics and muscle activation curves over the entire normalised time series. RESULTS: The functional outcomes of patients with concurrent LAI and OLT were significantly worse than those of healthy subjects preoperatively, but were partially improved postoperatively. Patients had decreased static and dynamic ROM preoperatively, and static ROM did not significantly increase postoperatively (preoperative, 39.6 ± 11.3; postoperative, 44.9 ± 7.1; healthy, 52.0 ± 4.6; p = 0.021). Patients showed increased dynamic ankle flexion ROM (preoperative, 41.2 ± 11.6; postoperative, 53.6 ± 9.0; healthy, 53.9 ± 3.4; p = 0.012) postoperatively, as well as increased peroneus longus activation (preoperative, 35.8 ± 12.0; postoperative, 55.4 ± 25.1; healthy, 71.9 ± 13.4; p = 0.002) and muscle co-contraction of the tibialis anterior and peroneus longus (preoperative, 69.4 ± 23.4; postoperative, 88.4 ± 9.3; healthy, 66.2 ± 18.1; p = 0.045). CONCLUSIONS: Patients with concurrent LAI and OLT had decreased static and dynamic sagittal ankle ROM and altered neuromuscular activation patterns. The arthroscopic modified Broström procedure and microfracture did not significantly increase the static sagittal ankle ROM. However, the dynamic sagittal ankle ROM, peroneus longus activation and muscle co-contraction of the tibialis anterior and peroneus longus increased postoperatively. LEVEL OF EVIDENCE: IV.


Assuntos
Fraturas de Estresse , Fraturas Intra-Articulares , Instabilidade Articular , Tálus , Tornozelo , Articulação do Tornozelo/cirurgia , Artroscopia/métodos , Humanos , Instabilidade Articular/cirurgia , Amplitude de Movimento Articular , Tálus/cirurgia , Resultado do Tratamento
14.
Org Lett ; 24(14): 2716-2721, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35388699

RESUMO

The first example of cyclization cross-coupling of tryptophols and tryptamines has been realized by copper catalysis with air or oxone as the terminal oxidant, resulting in the direct construction of a new class of heterocyclic 3a,3a'-bisindolines in moderate to good yields with high chemoselectivities. A series of mechanistic control experiments were also conducted, indicating that the copper catalyst selectively coordinates with the nitrogen moiety of the tryptamine to initiate the oxidation, and a nucleophilic-alkylation process is proposed for the carbon-carbon bond-forming in the reaction. The novel synthetic strategies and molecular skeletons outlined in this work provide new ideas and concepts for the design of other useful reaction and potential drugs.


Assuntos
Cobre , Indóis , Carbono , Catálise , Ciclização , Estrutura Molecular , Estresse Oxidativo , Triptaminas
15.
J Hazard Mater ; 426: 128089, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34933256

RESUMO

The dynamic network biomarkers (DNBs) are designed to identify the tipping point and specific molecules in initiation of PM2.5-induced lung cancers. To discover early-warning signals, we analyzed time-series gene expression datasets over a course of PM2.5 organic extraction-induced human bronchial epithelial (HBE) cell transformation (0th~16th week). A composition index of DNB (CIDNB) was calculated to determine correlations and fluctuations in molecule clusters at each timepoint. We identified a group of genes with the highest CIDNB at the 10th week, implicating a tipping point and corresponding DNBs. Functional experiments revealed that manipulating respective DNB genes at the tipping point led to remarkable changes in malignant phenotypes, including four promoters (GAB2, NCF1, MMP25, LAPTM5) and three suppressors (BATF2, DOK3, DAP3). Notably, co-altered expression of seven core DNB genes resulted in an enhanced activity of malignant transformation compared to effects of single-gene manipulation. Perturbation of pathways (EMT, HMGB1, STAT3, NF-κB, PTEN) appeared in HBE cells at the tipping point. The core DNB genes were involved in regulating lung cancer cell growth and associated with poor survival, indicating their synergistic effects in initiation and development of lung cancers. These findings provided novel insights into the mechanism of dynamic networks attributable to PM2.5-induced cell transformation.


Assuntos
Neoplasias Pulmonares , NF-kappa B , Biomarcadores , Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Material Particulado/toxicidade
16.
Front Pediatr ; 10: 1047227, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36619509

RESUMO

Objective: Selective dorsal rhizotomy (SDR) can decrease spasticity in children suffering from spastic cerebral palsy (SCP) and thus improve their moving ability when supplemented with the post-operational rehabilitation program. In this case, the study aims to investigate the gait changes in children with mild SCP after SDR in short-term follow-up. Methods: The information of ambulatory SCP cases who underwent SDR in our center was retrospectively reviewed, and comparisons of changes in spasticity, motor function and data of gait analysis before and after SDR were analyzed. Results: In total, 32 cases were included in this study, with a mean age of 5.9 ± 2.1 years old. Noticeable decrease was found in the median value of the pre-operational MAS score after SDR at last follow-up in both sides of adductors, gastrocnemius, soleus, and left hamstrings. The Gross Motor Function Measure-66 score increased from 70.6 ± 9.2 to 73.4 ± 8.2, and the gait deviation index increased after SDR compared with the pre-operational data (right side: 65.8 ± 8.8 vs. 60.1 ± 10.7; left side: 63.5 ± 10.1 vs. 57.0 ± 9.9). Noticeable changes were found that the maximum angle of affected ankles in the sagittal plane (the dorsal-flexion angle) increased from 2.5° to 8.2°, the angles at initial contact (1% gait cycle) of affected knees in the sagittal plane decreased from 34.0° to 27.8°, and the angles at the end of swing phase (100% gait cycle) of affected knees in the sagittal plane decreased from 35.8° to 28.3°. Conclusion: In short-term follow-up, SDR can lower spasticity in children with SCP. Post-operational gait analysis showed improvements in gross motor function and gait, which derived from the changes in the sagittal plane (ankle and knee). A longer follow-up duration is thus needed to clarify the long-term outcome.

17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(7): 832-837, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34412753

RESUMO

OBJECTIVE: To investigate the main postoperative complications, causes of death and the risk factors for survival in patient with benign end-stage lung diseases within 1 year after lung transplantation. METHODS: A retrospective analysis was conducted to collect the clinical data of 200 patients with benign end-stage lung disease who underwent lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from May 2017 to October 2018. The main postoperative complications, survival and causes of death within 1 year after operation were analyzed. The Kaplan-Meier method was used to plot survival curves, and the Log-Rank test was used to compare the influence of factors, including recipient's gender, use of marginal donor lung, primary disease, preoperative combination of moderate to severe pulmonary hypertension (PAH), intraoperative extracorporeal membrane oxygenation (ECMO) support, surgical methods, intraoperative massive blood loss, postoperative complications [infection, primary graft dysfunction (PGD), acute rejection], on 1-year survival in patients who underwent lung transplantation. The multivariate Cox proportional hazards regression model was used to evaluate the risk factors of death within 1 year after lung transplantation. RESULTS: Two hundred patients underwent successful lung transplantation. The major postoperative complications within 1 year after transplantation included infection in 131 patients, PGD in 20 patients, acute rejection in 57 patients, anastomotic complication in 26 patients and others (new onset diabetes, osteoporosis, etc.) in 53 patients. The 3-month, 6-month, and 1-year postoperative cumulative survival rates were 81.5%, 80.0% and 77.5%, respectively. Forty-five patients died during 1 year after operation, among whom 14 died of infection, 7 died of PGD, 8 died of acute rejection, 4 died of anastomotic complication, 3 died of cardio-cerebrovascular accident, 3 died of multiple organ failure, 2 died of respiratory failure and 4 died of other causes (traffic accident, etc.). The Kaplan-Meier survival analysis showed that recipient's gender, idiopathic pulmonary fibrosis (IPF) as the primary disease, preoperative combination of moderate and severe PAH, intraoperative ECMO support, intraoperative massive blood loss, postoperative complications (infection, PGD, acute rejection) were influencing factors for postoperative 1-year survival rate. The multivariate Cox regression model showed that male was the protective factor [hazard ratio (HR) = 0.481, 95% confidence interval (95%CI) was 0.244-0.947, P = 0.034], IPF as the primary disease (HR = 2.667, 95%CI was 1.222-5.848, P = 0.014), intraoperative use of ECMO support (HR = 1.538, 95%CI was 0.787-3.012, P = 0.028), massive blood loss during surgery (HR = 2.026, 95%CI was 0.976-4.205, P = 0.045) and postoperative infection (HR = 3.138, 95%CI was 1.294-7.608, P = 0.011), PGD (HR = 1.604, 95%CI was 0.464-5.539, P = 0.004), and acute rejection (HR = 1.897, 95%CI was 0.791-4.552, P = 0.015) were the independent risk factors for death within 1 year after transplantation. CONCLUSIONS: One-year survival rates after lung transplantation are affected by recipient's gender, primary disease, preoperative combination of moderate and severe PAH, intraoperative ECMO support, intraoperative massive blood loss, and postoperative complications (infection, PGD, acute rejection). The male is the protective factor, while IPF as the primary disease, intraoperative ECMO support, massive blood loss during surgery and postoperative complications (infection, PGD, acute rejection) are independent risk factors for death within 1 year after lung transplantation.


Assuntos
Fibrose Pulmonar Idiopática , Transplante de Pulmão , Humanos , Pulmão , Masculino , Estudos Retrospectivos , Fatores de Risco
18.
Comput Biol Med ; 134: 104436, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33984750

RESUMO

Clinical gait analysis incorporated with neuromusculoskeletal modelling could provide valuable information about joint movements and muscle functions during ambulation for children with cerebral palsy (CP). This study investigated how imposing pre-calculated joint angles during musculoskeletal model scaling influence the ankle joint angle and muscle force computation. Ten children with CP and equinus gait underwent clinical gait analysis. For each participant, a "default" (scaled without pre-calculated joint angles) and a "PJA" (scaled with pre-calculated ankle joint angles) model were generated to simulate their gait. Ankle joint angles were calculated with an inverse kinematic (IK) and direct kinematic (DK) approach. Triceps surae and tibialis anterior muscle forces were predicted by static optimisation and EMG-assisted modelling. We found that PJA-derived ankle angles showed a better agreement with what derived from the DK approach. The tibialis anterior muscle prediction was more likely to be affected by the scaling methods for the static optimisation approach and the gastrocnemius muscle force prediction was more likely to be influenced for the EMG-assisted modelling. This study recommends using the PJA model since the good consistency between IK and DK-derived joint angles facilitates communication among different research disciplines.


Assuntos
Paralisia Cerebral , Articulação do Tornozelo , Fenômenos Biomecânicos , Criança , Marcha , Humanos , Músculo Esquelético
19.
iScience ; 24(1): 101942, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33437933

RESUMO

A ceramic-based coating with a hierarchical surface structure was synthesized via solid-state reaction enabled by a double cathode glow discharge technique. This innovative coating comprises two distinct layers, specifically an outer layer with a well-aligned micro-pillar array and a dense inner layer. Both are composed of a face-centered cubic Cu(Co,Ni,Fe) solid solution phase together with a spinel-type Fe(Al,Cr)2O4 oxide. This coating exhibits superhydrophobicity and, yet, a very strong adhesion to water, i.e., the so-called "rose petal effect". This coating also exhibits highly efficient antibacterial ability against both Staphylococcus aureus and Escherichia coli bacteria under both dark and visible light conditions. The excellent antibacterial property originates from the synergistic effects through the release of Cu ions coupled with photothermal activity upon light activation.

20.
Ultrason Sonochem ; 71: 105406, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33310652

RESUMO

To alleviate the cavitation damage of metallic engineering components in hydrodynamic systems operating in marine environments, a NbN nanoceramic coating was synthesized on to a Ti-6Al-4V substrate via a double cathode glow discharge technique. The microstructure of the coating consisted of a ~13 µm thick deposition layer of a hexagonal δ'-NbN phase and a diffusion layer ~2 µm in thickness composed of face-centered cubic (fcc) B1-NaCl-structured (Ti,Nb)N. The NbN coating not only exhibited higher values of H/E and H2/E than those measured from NbN coatings deposited by other techniques, but also possessed good adhesion to the substrate. The cavitation erosion resistance of the NbN coating in a 3.5 wt% NaCl solution was investigated using an ultrasonic cavitation-induced apparatus combined with a range of electrochemical test methods. Potentiodynamic polarization measurements demonstrated that the NbN coated specimens demonstrated both a higher corrosion potential (Ecorr) and lower corrosion current density (icorr) than the uncoated substrate. Mott-Schottky analysis, combined with the point defect model (PDM), revealed that, for a given cavitation time, the donor density (ND) of the passive film on the NbN coating was reduced by 1 ~ 2 orders of magnitude relative to the uncoated Ti-6Al-4V, and the diffusivity of the point defects (D0) in the passive film grown on the NbN coating was nearly one order of magnitude lower than that on the uncoated substrate. In order to better understand the experimental observations obtained from Mott-Schottky analysis and double-charge layer capacitance measurements, first-principles density-functional theory was employed to calculate the energy of vacancy formation and the adsorption energy for chloride ions for the passive films present on both the NbN coating and bare Ti-6Al-4V.

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