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1.
Clin Exp Med ; 24(1): 102, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758367

RESUMEN

Immunotherapy is widely used in cancer treatment; however, only a subset of patients responds well to it. Significant efforts have been made to identify patients who will benefit from immunotherapy. Successful anti-tumor immunity depends on an intact cancer-immunity cycle, especially long-lasting CD8+ T-cell responses. Interferon (IFN)-α/ß/IFN-γ/interleukin (IL)-15 pathways have been reported to be involved in the development of CD8+ T cells. And these pathways may predict responses to immunotherapy. Herein, we aimed to analyze multiple public databases to investigate whether IFN-α/ß/IFN-γ/IL-15 pathways could be used to predict the response to immunotherapy. Results showed that IFN-α/ß/IFN-γ/IL-15 pathways could efficiently predict immunotherapy response, and guanylate-binding protein 1 (GBP1) could represent the IFN-α/ß/IFN-γ/IL-15 pathways. In public and private cohorts, we further demonstrated that GBP1 could efficiently predict the response to immunotherapy. Functionally, GBP1 was mainly expressed in macrophages and strongly correlated with chemokines involved in T-cell migration. Therefore, our study comprehensively investigated the potential role of GBP1 in immunotherapy, which could serve as a novel biomarker for immunotherapy and a target for drug development.


Asunto(s)
Proteínas de Unión al GTP , Inmunoterapia , Interferón-alfa , Interferón gamma , Interleucina-15 , Neoplasias , Humanos , Interleucina-15/genética , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/inmunología , Interferón gamma/metabolismo , Neoplasias/inmunología , Neoplasias/terapia , Inmunoterapia/métodos , Interferón beta , Linfocitos T CD8-positivos/inmunología , Transducción de Señal
2.
Transl Lung Cancer Res ; 13(3): 635-653, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38601447

RESUMEN

Background and Objective: Pulmonary sarcomatoid carcinoma (PSC) is a subset of non-small cell lung cancer (NSCLC) with highly malignant, aggressive, and heterogeneous features. Patients with this disease account for approximately 0.1-0.4% of lung cancer cases. The absence of comprehensive summaries on the basic biology and clinical treatments for PSC means there is limited systematic awareness and understanding of this rare disease. This paper provides an overview of the biological characteristics of PSC and systematically summarizes various treatment strategies available for patients with this disease. Methods: For this narrative review, we have searched literature related to the basic biology and clinical treatment approaches of PSC by searching the PubMed database for articles published from July 16, 1990 to August 29, 2023. The following keywords were used: "pulmonary sarcomatoid carcinoma", "genetic mutations", "immune microenvironment", "hypoxia", "angiogenesis", "overall survival", "surgery", "radiotherapy", "chemotherapy", and "immune checkpoint inhibitors". Key Content and Findings: Classical PSC comprises epithelial and sarcomatoid components, with most studies suggesting a common origin. PSC exhibits a higher tumor mutational burden (TMB) and mutation frequency than other types of NSCLC. The tumor microenvironment (TME) of PSC is characterized by hypoxia, hypermetabolism, elevated programmed cell death protein 1/programmed cell death-ligand 1 expression, and high immune cell infiltration. Treatment strategies for advanced PSC are mainly based on traditional NSCLC treatments, but PSC exhibits resistance to chemotherapy and radiotherapy. The advancement of genome sequencing has introduced targeted therapies as an option for mutation-positive PSC cases. Moreover, due to the characteristics of the immune microenvironment of PSC, many patients positively respond to immunotherapy, demonstrating its potential for the management of PSC. Conclusions: Although several studies have examined and assessed the TME of PSC, these are limited in quantity and quality, presenting challenges for research into the clinical treatment strategies for PSC. With the emergence of new technologies and the advancement of clinical research, for example, savolitinib's clinical study for MET exon 14 skipping mutations positive PSC patients have shown promising outcomes, more in-depth studies on PSC are eagerly anticipated.

3.
Lancet Reg Health West Pac ; 45: 101055, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38590780

RESUMEN

Background: Perceived delays in cancer drug approvals have been a major concern for policymakers in China. Policies have been implemented to accelerate the launch of new cancer drugs and indications. This study aimed to assess similarities and differences between China and the United States in the approvals, timing, and clinical benefit evidence of cancer drug indications between 2001 and 2020. Methods: This study retrospectively identified all cancer drugs and indications approved in both China and the United States from January 1st, 2001 to December 31, 2020, and described differences in approval times as well as in submission and review times. Information on the availability of overall survival benefit evidence by December 31, 2020, was collected. Univariate and multiple logistic regression analyses were used to assess whether evidence of benefit and other factors affected the propensity and timing of approvals of cancer drug indications in China. Findings: Between 2001 and 2020, 229 indications corresponding to 145 cancer drugs approved in the United States were identified. Of those, 80 indications (34.9%) were also approved in China by the end of 2020. Cancer drug indications were approved in China at a median of 1273.5 days after approval in the United States. The median submission and review time differences for cancer drug indications in China were 1198.0 days and 180.0 days respectively. Submission time differences accounted for most of the approval time differences (p < 0.001). Indications supported by overall survival benefit evidence had shorter median review time differences (145.0 days) than those without such evidence (235.0 days, p = 0.008). Indications with overall survival benefit evidence were 3.94 times more likely to be approved in China compared to those without such evidence (p = 0.001), controlling for approval year, cancer type, and the prevalence of cancer by site. Interpretation: FDA-approved cancer drug indications demonstrating a survival benefit were more likely to receive approvals in China with shorter regulatory review times compared to indications without such evidence. Given that manufacturer submission times were the main driver of cancer drug approval times in China, factors influencing submission timing should be explored. Funding: No funding.

4.
Molecules ; 29(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38474582

RESUMEN

Graphene quantum dots (GQDs) possess the photosensitive absorption for photoelectrochemical hydrogen evolution owing to special band structures, whereas they usually confront with photo-corrosion or undesired charge recombination during photoelectrochemical reactions. Hence, we establish the heterojunction between GQDs and MoSe2 sheets via a hydrothermal process for improved stability and performance. Photoanodic water splitting with hydrogen evolution boosted by the heteroatom doped N,S-GQDs/MoSe2 heterojunction has been attained due to the abundant active sites, promoted charge separation and transfer kinetics with reduced energy barriers. Diphasic 1T and 2H MoSe2 sheet-hybridized quantum dots contribute to the Schottky heterojunction, which can play a key role in expedited carrier transport to inhibit accumulative photo-corrosion and increase photocurrent. Heteroatom dopants lead to favored energy band matching, bandgap narrowing, stronger light absorption and high photocurrent density. The external quantum efficiency of the doped heterojunction has been elevated twofold over that of the non-doped pristine heterojunction. Modification of the graphene quantum dots and MoSe2 heterojunction demonstrate a viable and adaptable platform toward photoelectrochemical hydrogen evolution processes.

5.
J Appl Genet ; 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38340287

RESUMEN

Human epidermal growth factor receptor 2 (HER2) overexpression and activation are crucial for trastuzumab resistance in HER2-positive breast cancer; however, the potential regulatory mechanism of HER2 is still largely undetermined. In this study, a novel circular RNA derived from peptidylprolyl isomerase D (PPID) is identified as a negative regulator of trastuzumab resistance. Circ-PPID is highly stable and significantly downregulated in trastuzumab-resistant cells and tissues. Restoration of circ-PPID markedly enhances HER2-positive breast cell sensitivity to trastuzumab in vitro and in vivo. Circ-PPID directly binds to N-acetyltransferase 10 (NAT10) in the nucleus and blocks the interaction between NAT10 and HER2 mRNA, reducing N4-acetylcytidine (ac4C) modification on HER2 exon 25, leading to HER2 mRNA decay. Intriguingly, the subcellular localization of circ-PPID differs between trastuzumab-sensitive and -resistant cells. Circ-PPID in trastuzumab-resistant cells is located more in the cytoplasm, mainly due to the upregulation of Exportin 4 (XPO4), which results in the loss of spatial conditions for circ-PPID to bind to nuclear NAT10. Taken together, our data suggest that circ-PPID is a previously unappreciated ac4C-dependent HER2 epigenetic regulator, providing a promising therapeutic direction for overcoming trastuzumab resistance in clinical setting.

6.
Sci Adv ; 10(6): eadk6722, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38324693

RESUMEN

Reconstructing extensive cranial defects represents a persistent clinical challenge. Here, we reported a hybrid three-dimensional (3D) printed scaffold with modification of QK peptide and KP peptide for effectively promoting endogenous cranial bone regeneration. The hybrid 3D printed scaffold consists of vertically aligned cryogel fibers that guide and promote cell penetration into the defect area in the early stages of bone repair. Then, the conjugated QK peptide and KP peptide further regulate the function of the recruited cells to promote vascularization and osteogenic differentiation in the defect area. The regenerated bone volume and surface coverage of the dual peptide-modified hybrid scaffold were significantly higher than the positive control group. In addition, the dual peptide-modified hybrid scaffold demonstrated sustained enhancement of bone regeneration and avoidance of bone resorption compared to the collagen sponge group. We expect that the design of dual peptide-modified hybrid scaffold will provide a promising strategy for bone regeneration.


Asunto(s)
Osteogénesis , Andamios del Tejido , Criogeles , Regeneración Ósea/fisiología , Péptidos , Impresión Tridimensional
7.
Front Endocrinol (Lausanne) ; 15: 1340644, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38405152

RESUMEN

Background: Non-alcoholic fatty liver disease (NAFLD) is increasingly observed in non-obese individuals. The ZJU (Zhejiang University) index has been established as a new and efficient tool for detecting NAFLD, but the relationship between the ZJU index and NAFLD within non-obese individuals still remains unclear. Methods: A post-hoc evaluation was undertaken using data from a health assessment database by the Wenzhou Medical Center. The participants were divided into four groups based on the quartile of the ZJU Index. Cox proportional hazards regression, Kaplan-Meier analysis and tests for linear trends were used to evaluate the relationship between the ZJU index and NAFLD incidence. Subgroup analysis was conducted to test the consistency of the correlation between ZJU and NAFLD in subsgroups. Receiver operative characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the ZJU index, compared with the Atherogenic index of plasma (AIP) and Remnant lipoprotein cholesterol (RLP-C) index. Results: A total of 12,127 were included in this study, and 2,147 participants (17.7%) developed NAFLD in 5 years follow-up. Participants in higher ZJU quartiles tended to be female and have higher liver enzymes (including ALP, GGT, ALT, AST), GLU, TC, TG, LDL and higher NAFLD risk. Hazard Ratios (HR) and 95% confidence intervals (CI) for new-onset NAFLD in Q2, Q3, and Q4 were 3.67(2.43 to 5.55), 9.82(6.67 to 14.45), and 21.67(14.82 to 31.69) respectively in the fully adjusted model 3. With increased ZJU index, the cumulative new-onset NAFLD gradually increased. Significant linear associations were observed between the ZJU index and new-onset NAFLD (p for trend all<0.001). In the subgroup analysis, we noted a significant interaction in sex, with HRs of 3.27 (2.81, 3.80) in female and 2.41 (2.21, 2.63) in male (P for interaction<0.01). The ZJU index outperformed other indices with an area under the curve (AUC) of 0.823, followed by AIP (AUC=0.747) and RLP-C (AUC=0.668). Conclusion: The ZJU index emerges as a promising tool for predicting NAFLD risk in non-obese individuals, outperforming other existing parameters including AIP and RLP-C. This could potentially aid in early detection and intervention in this specific demographic.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Femenino , Humanos , Masculino , Pueblo Asiatico , China/epidemiología , Incidencia , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Estudios Prospectivos , Indicadores de Salud
8.
Orthop Surg ; 16(3): 523-531, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38272834

RESUMEN

There has been increasing application of autologous costal chondral/osteochondral transplantation (ACCT/ACOT) and costa-derived chondrocyte implantation (ACCI) for articular cartilage repair over the past three decades. This review presents the major evidence on the properties of costal cartilage and bone and their qualifications as grafts for articular cartilage repair, the major clinical applications, and the risks and strategies for costal chondral/osteochondral graft(s) harvest. First, costal cartilage has many specific properties that help restore the articular surface. Costa, which can provide abundant cartilage and cylindrical corticocancellous bone, preserves permanent chondrocyte and is the largest source of hyaline cartilage. Second, in the past three decades, autologous costal cartilage-derived grafts, including cartilage, osteochondral graft(s), and chondrocyte, have expanded their indications in trauma and orthopaedic therapy from small to large joints, from the upper to lower limbs, and from non-weight-bearing to weight-bearing joints. Third, the rate of donor-site complications of ACCT or ACOT is low, acceptable, and controllable, and some skills and accumulated experience can help reduce the risks of ACCT and ACOT. Costal cartilage-derived autografting is a promising technique and could be an ideal option for articular chondral lesions with or without subchondral cysts. More high-quality clinical studies are urgently needed to help us further understand the clinical value of such technologies.


Asunto(s)
Cartílago Articular , Cartílago Costal , Procedimientos Ortopédicos , Humanos , Cartílago Articular/cirugía , Cartílago Articular/lesiones , Condrocitos/trasplante , Trasplante Autólogo
9.
Small ; : e2309868, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38259052

RESUMEN

Critical-sized segmental long bone defects represent a challenging clinical dilemma in the management of battlefield and trauma-related injuries. The residual bone marrow cavity of damaged long bones contains many bone marrow mesenchymal stem cells (BMSCs), which provide a substantial source of cells for bone repair. Thus, a three-dimensional (3D) vertically aligned nanofiber scaffold (VAS) is developed with long channels and large pore size. The pore of VAS toward the bone marrow cavity after transplantation, enables the scaffolds to recruit BMSCs from the bone marrow cavity to the defect area. In vivo, it is found that VAS can significantly shorten gap distance and promote new bone formation compared to the control and collagen groups after 4 and 8 weeks of implantation. The single-cell sequencing results discovered that the 3D nanotopography of VAS can promote BMSCs differentiation to chondrocytes and osteoblasts, and up-regulate related gene expression, resulting in enhancing the activities of bone regeneration, endochondral ossification, bone trabecula formation, bone mineralization, maturation, and remodeling. The Alcian blue and bone morphogenetic protein 2 (BMP-2) immunohistochemical staining verified significant cartilage formation and bone formation in the VAS group, corresponding to the single-cell sequencing results. The study can inspire the design of next-generation scaffolds for effective long-bone regeneration is expected by the authors.

10.
Bioresour Technol ; 393: 130174, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38072081

RESUMEN

As dosing additives benefit for aerobic granular sludge (AGS) cultivation, effects of different concentrations (0, 10, 50 and 100 mg/L) of magnetic nanoparticles (Fe3O4 NPs) on aerobic granulation, contaminant removal and potential microbial community evolution related to acyl-homoserine lactones (AHLs) mediated bacterial communication were investigated with municipal wastewater. Results showed that the required time to achieve granulation ratio > 70 % was reduced by 60, 90 and 30 days in phase II with addition of 10, 50, 100 mg/L Fe3O4 NPs, respectively. 50 mg/L Fe3O4 NPs can improve contaminant removal efficiency. The promotion of relative abundance of AHLs-producing and AHLs-producing/quenching populations and AHLs-related functional genes accompanied with faster granulation. Iron-cycling-related bacteria were closely related with AHLs-related bacteria during AGS formation. Co-occurrence network analyses showed that AHLs-mediated communication may play an important role in coordinating microbial community composition and functional bacteria participating in nitrogen and polyphosphate metabolisms during aerobic granulation process.


Asunto(s)
Nanopartículas de Magnetita , Microbiota , Acil-Butirolactonas/metabolismo , Bacterias/metabolismo , Reactores Biológicos/microbiología , Percepción de Quorum , Aguas del Alcantarillado/microbiología
11.
Artículo en Inglés | MEDLINE | ID: mdl-37815966

RESUMEN

Steady-state visual evoked potential (SSVEP) based brain-computer interfaces (BCIs) have achieved an information transfer rate (ITR) of over 300 bits/min, but abundant training data is required. The performance of SSVEP algorithms deteriorates greatly under limited data, and the existing time-shift data augmentation method fails to improve it because the phase-locked requirement between training samples is violated. To address this issue, this study proposes a novel augmentation method, namely phase-locked time-shift (PLTS), for SSVEP-BCI. The similarity between epochs at different time moments was evaluated, and a unique time-shift step was calculated for each class to augment additional data epochs in each trial. The results showed that the PLTS significantly improved the classification performance of SSVEP algorithms on the BETA SSVEP datasets. Moreover, under the condition of one calibration block, by slightly prolonging the calibration duration (from 48 s to 51.5 s), the ITR increased from 40.88±4.54 bits/min to 122.61±7.05 bits/min with the PLTS. This study provides a new perspective on augmenting data epochs for training-based SSVEP-BCI, promotes the classification accuracy and ITR under limited training data, and thus facilitates the real-life applications of SSVEP-based brain spellers.


Asunto(s)
Interfaces Cerebro-Computador , Humanos , Potenciales Evocados Visuales , Electroencefalografía/métodos , Estimulación Luminosa , Encéfalo/fisiología , Algoritmos
12.
J Neural Eng ; 20(6)2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37816342

RESUMEN

Objective.Decoding different types of movements noninvasively from electroencephalography (EEG) is an essential topic in neural engineering, especially in brain-computer interface. Although the widely used sensorimotor rhythm (SMR) is efficient in limb decoding, it lacks efficacy in decoding movement frequencies. Accumulating evidence supports the notion that the movement frequency is encoded in the steady-state movement-related rhythm (SSMRR). Our study has two primary objectives: firstly, to investigate the spatial-spectral representation of SSMRR in EEG during voluntary movements; secondly, to assess whether movement frequencies and limbs can be effectively decoded based on SSMRR.Approach.To comprehensively examine the representation of SSMRR, we investigated the frequency characteristics and spatial patterns associated with various rhythmic finger movements. Coherence analysis was performed between the sensor or source domain EEG and finger movements recorded by data gloves. A fusion model based on spectral SNR features and filter-bank common spatial pattern features was utilized to decode movement frequencies and limbs.Main results.At the group-level, sensor domain, and source domain coherence maps demonstrated that the accurate movement frequency (f0) and its first harmonic (f1) were encoded in the contralateral motor cortex. For the four-class classification, including two movement frequencies for both hands, the decoding accuracies for externally paced and internally paced movements were 73.14 ± 15.86% and 66.30 ± 17.26% (averaged across ten subjects, chance levels at 31.05% and 30.96%). Notably, the average results of five subjects with the highest decoding accuracies reached 87.21 ± 7.44% and 80.44 ± 7.99%.Significance.Our results verified the EEG representation of SSMRR and proved that the movement frequency and limb could be effectively decoded based on spatial-spectral features extracted from SSMRR. We suggest that SSMRR can serve as a complement to SMR to expand the range of decodable movement types and the approaches of limb decoding.


Asunto(s)
Interfaces Cerebro-Computador , Extremidad Superior , Humanos , Electroencefalografía/métodos , Mano , Dedos , Movimiento
13.
J Med Virol ; 95(10): e29132, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37792307

RESUMEN

Esophageal squamous cell carcinoma (ESCC) may be correlated with HPV infection, and the mechanism underlying the ESCC formation induced by HPV16 infection remains elusive. Here, we overexpressed HPV16 E6 and E7 and coordinated the overexpression of these two genes in EPC2 and ESCC cells. We found that E7 and coordinated expression of E6 and E7 promoted the proliferation of EPC2 cells, and upregulation of shh was responsible for cell proliferation since the use of vismodegib led to the failure of organoid formation. Meanwhile, overexpression of E6 and E7 in ESCC cells promoted cell proliferation, migration, and invasion in vitro. Importantly, E6 and E7 coordinately increased the capability of tumor growth in nude mice, while vismodegib slowed the growth of tumors in NCG mice. Moreover, a series of genes and proteins changed in cell lines after overexpression of the E6 and E7 genes, the potential biological processes and pathways were systematically analyzed using a bioinformatics assay. Together, these findings suggest that the activation of the hedgehog pathway induced by HPV16 infection may initially transform basal cells in the esophagus and promote following malignant processes in ESCC cells. The application of hedgehog inhibitors may represent a therapeutic avenue for ESCC treatment.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Infecciones por Papillomavirus , Animales , Ratones , Proteínas Hedgehog/genética , Carcinoma de Células Escamosas de Esófago/genética , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/complicaciones , Neoplasias Esofágicas/genética , Ratones Desnudos
14.
Cell Death Discov ; 9(1): 399, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37891174

RESUMEN

Emerging evidence indicates that SOX2 is an oncogene for esophageal squamous cell carcinoma (ESCC). However, direct targeting of SOX2 is not feasible given that this transcription factor plays important roles in the maintenance of tissues such as the brain. Here, we identified CDP (Homeobox protein cut-like 1 or CASP) as a unique SOX2 binding partner enriched in ESCC with Duolink proximity ligation assay, bimolecular fluorescence complementation (BiFc) and immunoprecipitation. We then screened a peptide aptamer library using BiFc and immunoprecipitation and identified several peptide aptamers, including P58, that blocked the CDP/SOX2 interaction, leading to the inhibition of ESCC progress in vitro and in vivo. Upon administration, synthetic peptide P58, containing the YGRKKRRQRRR cell-penetrating peptide and the fluorophore TAMRA, also blocked the growth and metastasis of ESCC in both mice and zebrafish. Therefore, targeting the SOX2 binding partner CDP with peptide P58 offers an alternative avenue to treat ESCC with increased SOX2 levels.

15.
Orthop Surg ; 15(11): 2985-2992, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37649305

RESUMEN

OBJECTIVE: Osteochondral lesions of the talus (OLT) is a common and clinically challenging disease. The optimal management is still under debate. The purpose of this prospective study was to investigate the feasibility and clinical outcomes of autologous costal osteochondral transplantation (ACOT) for the treatment of cystic OLT. METHODS: From November 2021 to April 2023, five patients underwent autologous costal osteochondral transplantation (ACOT) for cystic OLT. The demographic data was described, including age, gender, lesion size and location. We prospectively evaluated their functional and imaging outcomes of the five patients for 12 months postoperatively, including numeric rating score (NRS) for pain when walking, Tegner score, American Orthopedic Foot & Ankle Society (AOFAS) score and Foot and Ankle Ability Measure (FAAM) score, and imaging results. A paired t-test was used for preoperative and postoperative comparison of the paired-design dataset. RESULTS: The average age was 36.6 ± 11.1 years. The average diameter of chondral lesions was 14.95 ± 2.71 mm, the average diameter of subchondral cysts was 10.66 ± 1.84 mm, and their average depth was 10.40 ± 1.86 mm. At 12 months postoperatively, the clinical function indexes improved significantly, including NRS (from 5.2 ± 2.3 to 0), Tegner score (from 3.2 ± 0.4 to 5.8 ± 0.4), AOFAS score (from 72.8 ± 10.0 to 98.2 ± 4.0), and FAAM score (FAAM/ADL from 61.2 ± 24.7 to 99.3 ± 1.6; FAAM/Sports from 32.5 ± 13.73 to 96.3 ± 8.4). Their magnetic resonance observation of cartilage repair tissue (MOCART) scores reached 78.0 ± 7.6 points. ICRS scores of three patients were nearly normal (10 or 11 points). The biopsy of the surviving grafts showed plenty of hyaline cartilage matrix and scattered chondrocytes histologically. No major severe complications were reported during the 12 months follow-up. CONCLUSION: ACOT could significantly relieve the symptoms of patients with OLT and improve their clinical function at short-term follow-up. ACOT might be a feasible and useful method for repairing OLT with subchondral cysts.


Asunto(s)
Quistes Óseos , Cartílago Articular , Astrágalo , Humanos , Adulto , Persona de Mediana Edad , Astrágalo/diagnóstico por imagen , Astrágalo/cirugía , Estudios Prospectivos , Cartílago , Trasplante Autólogo/métodos , Imagen por Resonancia Magnética/métodos , Quistes Óseos/diagnóstico por imagen , Quistes Óseos/cirugía , Quistes Óseos/patología , Trasplante Óseo/métodos , Cartílago Articular/cirugía , Resultado del Tratamiento
16.
Biomed Pharmacother ; 163: 114764, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37100016

RESUMEN

SOX2 is a transcription factor belonging to the SOX gene family, whose activity has been associated with the maintenance of the stemness and self-renewal of embryonic stem cells (ESCs), as well as the induction of differentiated cells into induced pluripotent stem cells (iPSCs). Moreover, accumulating studies have shown that SOX2 is amplified in various cancers, notably in esophageal squamous cell carcinoma (ESCC). In addition, SOX2 expression is linked to multiple malignant processes, including proliferation, migration, invasion, and drug resistance. Taken together, targeting SOX2 might shed light on novel approaches for cancer therapy. In this review, we aim to summarize the current knowledge regarding SOX2 in the development of esophagus and ESCC. We also highlight several therapeutic strategies for targeting SOX2 in different cancer types, which can provide new tools to treat cancers possessing abnormal levels of SOX2 protein.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Neoplasias Esofágicas/genética , Factores de Transcripción/metabolismo , Diferenciación Celular , Factores de Transcripción SOXB1/genética , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Línea Celular Tumoral
17.
Orthop Surg ; 15(1): 103-110, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36380533

RESUMEN

OBJECTIVE: The effectiveness of autologous osteoperiosteal transplantation (AOPT) for the treatment of large cystic talar osteochondral lesions (OCLs) should be further evaluated, and the postoperative cartilage coverage is questionable. The purpose of this retrospective observational study was to investigate the clinical outcomes of AOPT for the treatment of large cystic talar OCLs and to report second-look arthroscopic results. METHODS: From June 1, 2017, to June 1, 2021, all talar OCLs at our center were reviewed. Painful cystic lesions treated with AOPT were included in the study. The American Orthopaedic Foot and Ankle Society (AOFAS; 0-100 points) ankle-hindfoot score, Foot Function Index (FFI; 0-100 points), visual analog scale (VAS; 0-10 points) score, and Tegner score (0-10 points) were used to describe pain and functional outcomes. Furthermore, complications, patient-reported satisfaction degrees, imaging results (including computed tomography and magnetic resonance), and second-look arthroscopic evaluation data were also collected for analysis. RESULTS: A total of 29 cases were eligible for the study, and 26 responded to the latest follow-up request, with a mean follow-up duration of 30.2 (range, 12-57) months. The AOFAS score improved from 69.2 ± 10.9 preoperatively to 80.9 ± 10.0 at the latest follow-up (p = 0.000). The FFI score improved from 30.4 ± 18.4 preoperatively to 16.3 ± 14.0 at the latest follow-up (p = 0.000). The VAS pain score improved from 4.0 ± 2.1 preoperatively to 2.5 ± 2.0 at the latest follow-up (p = 0.001). No donor site morbidity was found. The mean postoperative MOCART score was 57.7 ± 9.5. Second-look arthroscopy showed a fibrillated cartilage-like surface at the lesion site in most cases, while two cases exhibited a nearly normal surface. CONCLUSION: The transplantation of osteoperiosteal cylinder autografts taken from the iliac crest for the treatment of large cystic talar OCLs yielded acceptable clinical results. Good integration of the bony part was observed, but cartilage regeneration remained uncertain.


Asunto(s)
Cartílago Articular , Astrágalo , Humanos , Astrágalo/cirugía , Cartílago , Trasplante Autólogo/métodos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X , Articulación del Tobillo/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Trasplante Óseo/métodos , Cartílago Articular/cirugía
18.
Development ; 149(24)2022 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-36420817

RESUMEN

Hematopoiesis is a highly coordinated process that generates all the body's blood cells, and perturbations in embryonic hematopoiesis may result in illnesses ranging from fetal anemia to various leukemias. Correct establishment of hematopoietic progenitor cell fate is essential for the development of adequate blood cell subpopulations, although regulators of cell fate commitment have not been fully defined. Here, we show that primary erythropoiesis and myelopoiesis in zebrafish embryos are synergistically regulated by blf and the drl cluster, as simultaneous depletion led to severe erythrocyte aplasia and excessive macrophage formation at the expense of neutrophil development. Integrative analysis of transcriptome- and genome-wide binding data revealed that blf and drl cluster genes are responsible for constraining the expression of vasculogenesis-promoting genes in the intermediate cell mass and monocytopoiesis-promoting genes in the rostral blood island. This indicates that blf and drl cluster genes act as determinants of the fate commitment of erythroid and myeloid progenitor cells. Furthermore, a rescue screen demonstrated that Zfp932 is a potential mammalian functional equivalent to zebrafish blf and drl cluster genes. Our data provide insight into conserved cell fate commitment mechanisms of primitive hematopoiesis.


Asunto(s)
Proteínas de Pez Cebra , Pez Cebra , Animales , Proteínas de Pez Cebra/metabolismo , Embrión no Mamífero/metabolismo , Regulación del Desarrollo de la Expresión Génica , Hematopoyesis/genética , Eritropoyesis/genética , Mamíferos/genética
19.
Cancer Biol Ther ; 23(1): 1-15, 2022 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-36131361

RESUMEN

ABBREVIATIONS: CCK-8, Cell Counting Kit 8; Chip, Chromatin Immunoprecipitation; EC, Esophageal cancer; EMT, epithelial-to-mesenchymal transition; ESCC, Esophageal squamous cell carcinomas; LLGL2, lethal (2) giant larvae protein homolog 2; LLGL2ov, LLGL2 overexpression; MET, mesenchymal-epithelial transition; miRNAs, MicroRNAs; PRM-MS, Parallel reaction monitoring-Mass spectrometry; SD, Standard deviation; SOX, sex determining region Y (SRY)-like box; SOX2-Kd, SOX2-knockdwon; TUNEL, TdT-mediated dUTP Nick-End Labeling.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo
20.
Artículo en Inglés | MEDLINE | ID: mdl-35853068

RESUMEN

Brain-computer interface (BCI) usually suffers from the problem of low recognition accuracy and large calibration time, especially when identifying motor imagery tasks for subjects with indistinct features and classifying fine grained motion control tasks by electroencephalogram (EEG)-electromyogram (EMG) fusion analysis. To fill the research gap, this paper presents an end-to-end semi-supervised learning framework for EEG classification and EEG-EMG fusion analysis. Benefiting from the proposed metric learning based label estimation strategy, sampling criterion and progressive learning scheme, the proposed framework efficiently extracts distinctive feature embedding from the unlabeled EEG samples and achieves a 5.40% improvement on BCI Competition IV Dataset IIa with 80% unlabeled samples and an average 3.35% improvement on two public BCI datasets. By employing synchronous EMG features as pseudo labels for the unlabeled EEG samples, the proposed framework further extracts deep level features of the synergistic complementarity between the EEG signals and EMG features based on the deep encoders, which improves the performance of hybrid BCI (with a 5.53% improvement for the Upper Limb Motion Dataset and an average 4.34% improvement on two hybrid datasets). Moreover, the ablation experiments show that the proposed framework can substantially improve the performance of the deep encoders (with an average 5.53% improvement). The proposed framework not only largely improves the performance of deep networks in the BCI system, but also significantly reduces the calibration time for EEG-EMG fusion analysis, which shows great potential for building an efficient and high-performance hybrid BCI for the motor rehabilitation process.


Asunto(s)
Interfaces Cerebro-Computador , Algoritmos , Electroencefalografía , Electromiografía , Humanos , Imaginación , Aprendizaje Automático Supervisado
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