RESUMO
PURPOSE: Head and neck cancer cells commonly express programmed death ligand 1 (PD-L1) and epidermal growth factor receptor (EGFR), both of which play pivotal roles in the antitumor cellular immune response. Pembrolizumab, a PD-1 inhibitor, and cetuximab, an EGFR inhibitor, are typically effective agents combined with neoadjuvant platinum-based chemotherapy for the treatment of head and neck squamous cell carcinoma (HNSCC). This study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with HNSCC. METHODS: Patients with HNSCC underwent radical surgery and complete cervical lymph node dissection following neoadjuvant immunochemotherapy at RenJi Hospital from January 2021 to June 2024 were retrospectively analyzed. The primary endpoint was major pathological response (MPR). We further explored the relationship between the efficacy and immune estimators. FINDINGS: Twenty-one patients were enrolled in this retrospective study. The MPR was 66.7%, including 11 patients who achieved a pathological complete response (pCR). The overall response rate (ORR) was 90.5%, and the complete response (CR) rate was 28.6%. The oropharynx, as the primary site, was the sensitive tumor type to neoadjuvant immunochemotherapy. The most common adverse event (AEs) was anemia (61.9%). No grade 4 AE or delayed surgery was reported. Laryngeal preservation rates were 90.9% (10/11), and pathological findings confirmed negative surgical margins for all patients. Moreover, pre-treatment peripheral lymphocyte count, monocyte count, and platelet to lymphocyte ratio (PLR) displayed a significant correlation with the treatment response. CONCLUSION: Pembrolizumab plus cetuximab with chemotherapy for patients with HNSCC is a feasible and safe clinical protocol fulfilling organ preservation and life quality improvement. Pre-treatment peripheral immune estimators could help to screen patients who may respond to the neoadjuvant immunochemotherapy.
RESUMO
Background: Nurses' competencies are crucial for infectious disease prevention and control. We aimed to investigate competencies in responding to infectious disease outbreaks of nurses in primary healthcare institutions and identify their training needs. Methods: A cross-sectional study was conducted from June to September 2022, recruiting nurses from primary healthcare institutions across Sichuan Province. Their competencies and training needs were assessed using a modified Emergency Response Competency Scale for Infectious Diseases. Additionally, their sociodemographic characteristics and experience in infectious disease outbreak trainings were collected. Univariate analyses were used to compare competencies and training needs by participant characteristics. Multiple linear regression was conducted to identify determinants of their competencies. Results: A total of 1,439 nurses from 44 primary healthcare institutions participated in this study. The overall competency and training needs had a median of 3.6 (IQR [3.1, 4.0]) and 4.0 (IQR [3.9, 4.7]), respectively. Age (ß = -0.074, p = 0.005), experience in higher authority hospitals (ß = 0.057, p = 0.035), infectious disease outbreak trainings attended within the last 5 years (ß = 0.212, p < 0.001), and regions where the institutions located were determinants of the competencies. Conclusion: The competencies in responding to infectious disease outbreaks among nurses in primary healthcare institutions were at a moderate level, influenced by varied factors.
Assuntos
Competência Clínica , Surtos de Doenças , Atenção Primária à Saúde , Humanos , Estudos Transversais , Feminino , Adulto , Masculino , Competência Clínica/estatística & dados numéricos , China/epidemiologia , Inquéritos e Questionários , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/estatística & dados numéricosRESUMO
OBJECTIVES: Career self-management is believed to be a critical behaviour in the new career era. However, the underlying mechanisms that stimulate nurses' career self-management are unclear. The aim of this study was to examine the mediating effect of self-efficacy and the moderating effect of proactive personality on the relationship between perceived organisational support and career self-management among nurses. DESIGN: This was a cross-sectional survey. SETTING AND PARTICIPANTS: A total of 1866 nurses from 15 hospitals across 15 cities in China were recruited for this study. PRIMARY AND SECONDARY OUTCOME MEASURES: The Perceived Organizational Support Scale, General Self-efficacy Scale, Proactive Personality Scale and Individual Career Management Questionnaire were used. Data were analysed using moderated mediation regressions with Hayes' PROCESS macro in SPSS version 26.0. RESULTS: General self-efficacy mediated the relationship between perceived organisational support and career self-management. Proactive personality moderated the direct (B=0.043, p<0.001, 95% CI 0.026 to 0.060) and indirect relationship (B=0.098, p<0.001, 95% CI 0.074 to 0.123) between perceived organisational support and career self-management. Further, the positive effects of perceived organisational support on general self-efficacy and career self-management were stronger for nurses with a high level of proactive personality. The model explained 47.2% of the variance in career self-management. CONCLUSION: The findings highlight the crucial benefits of self-efficacy and important conditional effects of perceived organisational support on nurses' career self-management.
Assuntos
Personalidade , Autoeficácia , Humanos , Feminino , Estudos Transversais , Masculino , Adulto , China , Inquéritos e Questionários , Autogestão/psicologia , Análise de Mediação , Cultura Organizacional , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/psicologia , Satisfação no Emprego , Enfermeiras e Enfermeiros/psicologia , Atitude do Pessoal de Saúde , Apoio SocialRESUMO
The pervasive presence of methylsiloxanes (MSs), comprising linear and cyclic congeners, in the environment poses significant ecological risks, yet the understanding of their transport mechanisms and deposition patterns remains limited. This study analyzed the concentrations of 12 linear-MSs (L3-L14) and 7 cyclic-MSs (D3-D9) in 29 surface soil samples collected across varying altitudes (3726 to 4863 m) near the Jiama mining sector in Tibet, aiming to investigate the distribution and transport dynamics of MSs from the emission source. The distribution of total MS concentration (ranging from 50.1 to 593 ng/g) showed a remarkable correlation with proximity to the mining site, suggesting the emergent source of mining activities for the MSs in the remote environment of the Tibetan Plateau. Employing the innovative model of robust absolute principal component scores-robust geographically weighted regression (RAPCS-RGWR), the analysis predicted that the mining operations contributing 57.1 % of the total soil MSs, would significantly surpass contributions from traffic emissions (14.7 %), residential activities (13.2 %), and the environmental factor of total organic matter content (14.9 %). The Boltzmann equation effectively modeled the distribution pattern of soil MSs, highlighting atmospheric transport and gravitational settling as key distribution mechanisms. However, linear-MSs exhibited longer transport distances than cyclic-MSs and were more profoundly affected by prevailing wind directions, suggesting their differential environmental behaviors and risks. Our study underscored that the mining sector possibly emerged as a significant source of Tibetan MSs, and provided insights into the transport and fate of MSs in remote, high-altitude environments. The findings emphasize the need for targeted pollution control strategies to mitigate the environmental footprint of mining activities in Tibet and similar regions.
RESUMO
During growth phase, antlers exhibit a very rapid rate of chondrogenesis. The antler is formed from its growth center reserve mesenchyme (RM) cells, which have been found to be the derivatives of paired related homeobox 1 (Prrx1)-positive periosteal cells. However, the underlying mechanism that drives rapid chondrogenesis is not known. Herein, the miRNA expression profiles and chromatin states of three tissue layers (RM, precartilage, and cartilage) at different stages of differentiation within the antler growth center were analyzed by RNA-sequencing and ATAC-sequencing. We found that miR-140-3p was the miRNA that exhibited the greatest degree of upregulation in the rapidly growing antler, increasing from the RM to the cartilage layer. We also showed that Prrx1 was a key upstream regulator of miR-140-3p, which firmly confirmed by Prrx1 CUT&Tag sequencing of RM cells. Through multiple approaches (three-dimensional chondrogenic culture and xenogeneic antler model), we demonstrated that Prrx1 and miR-140-3p functioned as reciprocal negative feedback in the antler growth center, and downregulating PRRX1/upregulating miR-140-3p promoted rapid chondrogenesis of RM cells and xenogeneic antler. Thus, we conclude that the reciprocal negative feedback between Prrx1 and miR-140-3p is essential for balancing mesenchymal proliferation and chondrogenic differentiation in the regenerating antler. We further propose that the mechanism underlying chondrogenesis in the regenerating antler would provide a reference for helping understand the regulation of human cartilage regeneration and repair.
Assuntos
Chifres de Veado , Proteínas de Homeodomínio , MicroRNAs , Animais , Cartilagem/metabolismo , Diferenciação Celular/genética , Condrogênese/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
The photodegradation products (PDPs) of antibiotics in the aquatic environment received increasing concern, but their chronic effects on microalgae remain unclear. This study initially focused on examining the acute effects of erythromycin (ERY), then explored the chronic impacts of ERY PDPs on Chlorella pyrenoidosa. ERY of 4.0 - 32 mg/L ERY notably inhibited the cell growth and chlorophyll synthesis. The determined 96 h median effective concentration of ERY to C. pyrenoidosa was 11.78 mg/L. Higher concentrations of ERY induced more serious oxidative damage, antioxidant enzymes alleviated the oxidative stress. 6 PDPs (PDP749, PDP747, PDP719, PDP715, PDP701 and PDP557) were identified in the photodegradation process of ERY. The predicted combined toxicity of PDPs increased in the first 3 h, then decreased. Chronic exposure showed a gradual decreasing inhibition on microalgae growth and chlorophyll content. The acute effect of ERY PDPs manifested as growth stimulation, but the chronic effect manifested as growth inhibition. The malonaldehyde contents decreased with the degradation time of ERY at 7, 14 and 21 d. However, the malonaldehyde contents of ERY PDPs treatments were elevated compared to those in the control group after 21 d. Risk assessment still need to consider the potential toxicity of degradation products under long-term exposure.
Assuntos
Chlorella , Clorofila , Eritromicina , Microalgas , Fotólise , Poluentes Químicos da Água , Chlorella/efeitos dos fármacos , Chlorella/efeitos da radiação , Eritromicina/toxicidade , Eritromicina/farmacologia , Poluentes Químicos da Água/toxicidade , Microalgas/efeitos dos fármacos , Clorofila/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Antibacterianos/toxicidade , Antibacterianos/farmacologia , Malondialdeído/metabolismoRESUMO
BACKGROUND: Type 1 diabetes mellitus (T1D) represents a severe threat to human health. Persistent hyperglycemia and dyslipidemia can lead to damaged liver function, while effective interventions for these complications are currently lacking. Deer antler stem cells (AnSCs), a novel type of adult stem cells, significantly reduced liver injury, which was speculated to be achieved through the paracrine pathway. METHODS: In this study, AnSC-conditioned medium (AnSC-CM) was used to treat C57BL/6 mice with T1D symptoms induced by streptozotocin (STZ). The therapeutic effects of AnSC-CM on T1D were evaluated, and the underlying mechanism was investigated. RESULTS: It was shown that AnSC-CM alleviated the T1D symptom: decreased body weight, increased blood glucose levels and islet lesions, and reduced insulin secretion. Moreover, AnSC-CM treatment improved liver function and mitigated liver injury in T1D mice. Impressively, the therapeutic effects of AnSC-CM on T1D were better than those of bone marrow mesenchymal stem cell-CM (BMSC-CM). The mechanistic study revealed that AnSC-CM significantly downregulated the NF-κB signaling pathway in both pancreatic and liver tissues. CONCLUSIONS: Therapeutic effects of AnSC-CM on STZ-induced T1D and liver injury may be achieved through targeting the NF-κB signaling pathway.
Assuntos
Chifres de Veado , Cervos , Diabetes Mellitus Tipo 1 , Adulto , Animais , Humanos , Camundongos , Chifres de Veado/citologia , Chifres de Veado/metabolismo , Meios de Cultivo Condicionados/farmacologia , Diabetes Mellitus Tipo 1/terapia , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais , Células-Tronco/metabolismoRESUMO
Hepatic stellate cell (HSC) activation is a crucial step in the development of liver fibrosis. Previous studies have shown that antler stem cells (AnSCs) inhibited HSC activation, suggesting that this may be achieved through secreting or releasing peptides. This study aimed to investigate whether AnSC-derived peptides (AnSC-P) could reduce liver fibrosis. The results showed that AnSC-P effectively reduced liver fibrosis in rats. Furthermore, we found that thymosin ß10 (Tß-10) was rich in AnSC-P, which may be the main component of AnSC-P contributing to the reduction in liver fibrosis. A further study showed that Tß-10 reduced liver fibrosis in rats, with a reduction in HYP and MDA levels in the liver tissues, a decrease in the serum levels of ALP, ALT, AST, and TBIL and an increase in TP and ALB. Moreover, Tß-10 decreased the expression levels of the genes related to the TGF-ß/SMAD signaling pathway in vivo. In addition, Tß-10 also inhibited TGF-ß1-induced HSC activation and decreased the expression levels of the TGF-ß/SMAD signaling pathway-related genes in HSCs in vitro. In conclusion, antler Tß-10 is a potential drug candidate for the treatment of liver fibrosis, the effect of which may be achieved via inhibition of the TGFß/SMAD signaling pathway.
Assuntos
Chifres de Veado , Timosina , Fator de Crescimento Transformador beta1 , Ratos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Chifres de Veado/metabolismo , Proteínas Smad/metabolismo , Células Estreladas do Fígado , Cirrose Hepática/induzido quimicamente , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Allergic rhinitis (AR) is a prevalent immune-related allergic disease, and corticosteroid nasal sprays serve as the primary treatment for this patient population. However, their short duration of efficacy and frequent administration pose challenges, leading to drug wastage and potential adverse effects. To overcome these limitations, we devised a novel approach to formulate DEX-Gel by incorporating dexamethasone (DEX) into a blend of Pluronic F127, stearic acid (SA), and polyethylene glycol 400 (PEG400) to achieve sustained-release treatment for AR. RESULTS: Following endoscopic injection into the nasal mucosa of AR rats, DEX-Gel exhibited sustained release over a 14-day period. In vivo trials employing various assays, such as flow cytometry (FC), demonstrated that DEX-Gel not only effectively managed allergic symptoms but also significantly downregulated helper T-cells (TH) 2 and TH2-type inflammatory cytokines (e.g., interleukins 4, 5, and 13). Additionally, the TH1/TH2 cell ratio was increased. CONCLUSION: This innovative long-acting anti-inflammatory sustained-release therapy addresses the TH1/TH2 immune imbalance, offering a promising and valuable approach for the treatment of AR and other inflammatory nasal diseases.
Assuntos
Rinite Alérgica , Células Th1 , Humanos , Ratos , Animais , Camundongos , Preparações de Ação Retardada/farmacologia , Células Th2 , Rinite Alérgica/tratamento farmacológico , Citocinas , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Ovalbumina , Camundongos Endogâmicos BALB CRESUMO
Shikonin (SHK) has been evidenced to possess effects against various cancer cells. However, poor aqueous solubility and high toxicity restrict its application. In the study, RGD-decorated liposomes loaded with SHK (RGD-Lipo-SHK) were prepared via thin-film hydration method. Characterization and cellular uptake of liposomes was evaluated. Cytotoxicity of blank liposomes and different SHK formulations was measured against breast cancer cells (MDA-MB-231, MCF-7, and MCF-10A). Anti-tumour effects and pharmacokinetic parameters of different SHK formulations were appraised in tumour spheroids and in rat model, respectively. Liposomes displayed a particle size of less than 127 nm with a polydispersity index about 0.21. The encapsulation efficiency was about 91% for SHK, and drug leakage rate of liposomes was less than 6%. RGD-Lipo-SHK showed superior cellular internalization in the αvß3-positive MDA-MB-231 cells. Blank liposomes had no cytotoxicity to MDA-MB-231 and MCF-7 cells. Howbeit, different SHK formulations obviously inhibited proliferation of MCF-10A cells, especially free SHK. Meanwhile, RGD-Lipo-SHK significantly inhibited growth inhibition of tumour spheroids. The pharmacokinetics study indicated that the peak concentration, area under plasma concentration-time curves, half-life, and mean residence time of RGD-Lipo-SHK distinctly increased compared with those of free SHK. Altogether, these results demonstrated RGD-Lipo-SHK could reduce cytotoxicity, strengthen the antitumor-targeted effect, and prolong circulation time, which provides a foundation for further in vivo experimentations.
Assuntos
Lipossomos , Naftoquinonas , Humanos , Ratos , Animais , Naftoquinonas/farmacologia , Células MCF-7 , Oligopeptídeos , Linhagem Celular TumoralRESUMO
OBJECTIVE: This study assesses the difference in professional attitudes among medical students, both before and after coronavirus disease 2019 (COVID-19), and identifies the determinants closely associated with it, while providing precise and scientific evidence for implementing precision education on such professional attitudes. METHODS: A pre-post-like study was conducted among medical students in 31 provinces in mainland China, from March 23, to April 19, 2021. RESULTS: The proportion of medical students whose professional attitudes were disturbed after the COVID-19 pandemic, was significantly lower than before the COVID-19 pandemic (χ2 = 15.6216; P < 0.0001). Compared with the "undisturbed -undisturbed" group, the "undisturbed-disturbed" group showed that there was a 1.664-fold risk of professional attitudes disturbed as grade increased, 3.269-fold risk when others suggested they choose a medical career rather than their own desire, and 7.557-fold risk for students with COVID-19 in their family, relatives, or friends; while the "disturbed-undisturbed" group showed that students with internship experience for professional attitudes strengthened was 2.933-fold than those without internship experience. CONCLUSIONS: The professional attitudes of medical students have been strengthened during the COVID-19 pandemic. The results provide evidence of the importance of education on professional attitudes among medical students during public health emergencies.
Assuntos
COVID-19 , Estudantes de Medicina , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , EscolaridadeRESUMO
Extracellular vesicles (EVs) from antler reserve mesenchymal (RM) cells play an important role in the paracrine regulation during rapid growth of antler without forming a tumor; therefore, RM-EVs become novel materials for anti-tumor studies, such as osteosarcoma treatment. However, the problem of low production of RM-EVs in traditional 2D culture limits its mechanism research and application. In this study, we established an optimal 3D culture system for antler RM cells to produce EVs (3D-RM-EVs). Morphology and property of harvested 3D-RM-EVs were normal compared with EVs from conventional 2D culture, and the miRNA profile in them was basically the same through transcriptome sequencing analysis. Based on the same number of RM cells, the volume of the culture medium collected by 3D cultural system concentrated nearly 30 times, making it more convenient for subsequent purification. In addition, EVs were harvested 30 times in 3D cultural system, greatly increasing the total amount of EVs (harvested a total of 2-3 times in 2D culture). Although 3D-RM-EVs had a limited inhibitory effect on the proliferation of K7M2 cells, the inhibition effect of 3D-RM-EVs loaded drugs (Ifosfamide + Etoposide) were more significant than that of positive drug group alone (P < 0.05). Furthermore, in vivo studies showed that 3D-RM-EVs loaded drugs (Ifosfamide + Etoposide) had the most significant tumor inhibition effect, with decreased tumor size, and could slow down body weight loss compared with Ifosfamide + Etoposide (IFO + ET) group. These results demonstrated that 3D-RM-EVs were efficiently prepared from antler RM cells and were effective as drug vehicles for the treatment of osteosarcoma.
Assuntos
Chifres de Veado , Neoplasias Ósseas , Vesículas Extracelulares , Células-Tronco Mesenquimais , Osteossarcoma , Animais , Humanos , Etoposídeo , Ifosfamida , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológicoRESUMO
INTRODUCTION: The typical outcome of mammalian wound healing is scarring, a fibrotic process mediated by myofibroblast aggregation. Perfect healing in a clinical setting is relatively unexplored. Surprisingly, our previous studies have shown that the large wound (10 cm diameter or more) of the pedicle of deer naturally achieves regenerative restoration, realized through a paracrine pathway from adjacent antler stem cells (AnSCs). METHODS: AnSC-derived exosomes (AnSC-exos) were topically injected around the full-thickness wounds in a rat model. The effects on the rate of wound healing and the quality of healing were evaluated via morphological, histological, and molecular biological techniques on days 14 and 28 after surgery. RESULTS: The results showed that AnSC-exos significantly accelerated the rate of wound healing and improved healing quality, including regeneration of cutaneous appendages (hair follicles and sebaceous glands) and the distribution pattern of collagen (basket-weave-like) in the healed skin. These effects of AnSC-exos were comparable to those of AnSCs but were significantly more potent than those of exosomes derived from bone marrow mesenchymal stem cells (bMSC-exos). Furthermore, AnSC-exos treatment effectively inhibited fibroblast-to-myofibroblast transition (FMT), as evidenced by the reduction of full-thickness skin injury-induced FMT in vivo and TGF-ß1-induced FMT in vitro. CONCLUSION: AnSC-exos could effectively promote regenerative cutaneous wound healing, highly likely through FMT inhibition. This suggests that AnSC-exos treatment could provide the potential for a novel approach to induce regenerative wound healing in the clinical setting.
RESUMO
Background: It is well known that motor features of Parkinson's disease (PD) commonly begin on one side of the body and extend to the other side with disease progression. The onset side generally remains more severely affected over the course of the disease. However, the pathophysiology underlying the asymmetry of motor manifestations remains unclear. The purpose of the present study is to examine whether alterations in neuronal activity in the subthalamic nucleus (STN) associate with PD severity. Methods: Microelectrode recording was performed in the STN during targeting for 30 patients in the treatment of deep brain stimulation. The mean spontaneous firing rate (MSFR), power density spectral analysis, and correlations were calculated. Characteristics of subthalamic oscillatory activity were compared between two hemispheres. UPDRS III scores during "Off" and "On" states were obtained for the body side of initial symptoms (BSIS) and the body side of extended symptoms (BSES). Results: There were significant differences of MSFR (41.3 ± 11.0 Hz vs 35.2 ± 10.0 Hz) and percentage of ß frequency oscillatory neurons (51.3% vs 34.9%) between BSIS and BSES. The percentage of ß frequency oscillatory neurons correlated with the bradykinesia/rigidity scores for both sides (p < 0.05). In contrast, the percentage of tremor frequency oscillatory neurons was significantly higher in the BSES than that in the BSIS. In particular, these neurons only correlated with the tremor scores of the BSES (p < 0.05). Conclusion: The results suggest that increased neuronal firing rate and ß frequency oscillatory neurons in the STN are associated with contralateral side motor severity and its progression. Tremor frequency oscillatory neurons are less observed in the STN of the BSIS suggesting that ß oscillatory activity dominates and tremor frequency oscillatory activity reciprocally declines.
RESUMO
Pulmonary fibrosis (PF), a chronic interstitial lung disease, is characterized by over-abundant deposition of extracellular matrix consisting mainly of collagen I. In previous studies, we demonstrated that deer antler stem cells (AnSCs), a novel type of adult stem cell, are capable of significantly down-regulating collagen formation in different organs and tissues and speculated that they could effectively treat PF via reducing collagen deposition in the lung tissue. In the present study, we found that administration of AnSCs improved the survival rate of PF mice and reduced lung fibrosis, collagen deposition and myofibroblast differentiation. The effects of AnSC treatment were significantly better than the positive control (adipose-derived stem cells). Interestingly, AnSC-Exos were almost equally effective as AnSCs in treating PF, suggesting that the effects of AnSCs on reduction of PF may be mainly through a paracrine mechanism. Further, AnSC-Exos reduced the number of M2 macrophages, a type of macrophage that secrets pro-fibrotic factors to accelerate fibrotic progression, in the lung tissues. In vitro experiments showed that the effects of AnSC-Exos on macrophage modulation were likely achieved via inhibition of the recruitment of circulating monocyte-derived macrophages (reducing the number of macrophages), rather than via inhibition of M2 polarization of macrophages. Inhibition of macrophage recruitment by AnSCs may be achieved indirectly via inhibiting CCL7 expression in fibroblasts; both let-7b and let-7a were highly enriched in AnSC-Exos and may play a critical role in the inhibition of CCL7 expression of fibroblasts. Collectively, the use of antler stem cells or their exosomes opens up a novel strategy for PF treatment in the clinical setting.
RESUMO
Antlerogenic periosteum (AP) is the unique tissue type that gives rise to antlers and their antecedents, the pedicles. Deer antlers are the only mammalian organ that can fully regenerate. Efficient investigation of the mechanism of antler formation and regeneration requires year-round availability of AP, but naturally AP can only be obtained less than two months in a year. In the present study we took the cryopreservation approach to store the sampled AP in ultra-low temperature to overcome the limited period of availability. First, we evaluated the suitability of vitrification and cell cryopreservation method for cryopreservation of AP, cell migration status of the AP tissue pieces confirmed that vitrification methods did not work as the only few AP cells migrated out, whereas migrated cell numbers in the cell-cryo group (conventional method for cryopreservation of cells) were comparable to those of the fresh AP group. To further evaluate the suitability of cell cryopreservation method for AP tissue, AP samples were allocated into three groups based on the different ratios of cryopreservation reagents (dimethyl sulfoxide [DMSO], dulbecco's modified eagle's medium [DMEM] and fetal bovine serum [FBS]): AP-Cell-1 (1:4:5), AP-Cell-2 (1:2:7) and AP-Cell-3 (1:0:9), the results showed that migrated cell number were again comparable to the fresh AP group. There was no significant difference between the cell-cryo groups (AP-Cell-1 and AP-Cell-3) and the fresh group: (1) in viability (p > 0.05) through trypan blue staining (91.2%, 90.8%, and 92.4%, respectively); (2) in the attachment day, and all on Day 5 after cell seeding; (3) in cell proliferation rate (p > 0.05) through Cell Counting kit 8 (CCK8) measurement; and (4) in number of the formed clones (Clonogenicity). In the in vivo trials, there was no visible difference in temporal differentiation sequence of the formed xenogeneic antlers between the fresh AP and cryopreserved AP (AP-Cell-1 and AP-Cell-3). Overall, we found that the AP tissue was well cryopreserved just using the conventional freezing and thawing methods for cells, and their viability and developmental potential comparable to the fresh AP both in vitro and in vivo. The long-term preservation of the AP tissue is of great significance for the study of the periosteum biology in general and the mechanism underlying xenogeneic generation and regeneration of deer antlers in specific.
Assuntos
Chifres de Veado , Cervos , Animais , Cervos/fisiologia , Periósteo/fisiologia , Regeneração , Criopreservação/veterinária , Chifres de Veado/fisiologiaRESUMO
Gene expression plays a critical role in the pathogenesis of Parkinson's disease (PD). How gene expression profiles are correlated with functional-metabolic architecture remains obscure. We enrolled 34 PD patients and 25 age-and-sex-matched healthy controls for simultaneous 18 F-FDG-PET/functional MRI scanning during resting state. We investigated the functional gradients and the ratio of standard uptake value. Principal component analysis was used to further combine the functional gradients and glucose metabolism into functional-metabolic architecture. Using partial least squares (PLS) regression, we introduced the transcriptomic data from the Allen Institute of Brain Sciences to identify gene expression patterns underlying the affected functional-metabolic architecture in PD. Between-group comparisons revealed significantly higher gradient variation in the visual, somatomotor, dorsal attention, frontoparietal, default mode, and subcortical network (pFDR < .048) in PD. Increased FDG-uptake was found in the somatomotor and ventral attention network while decreased FDG-uptake was found in the visual network (pFDR < .008). Spatial correlation analysis showed consistently affected patterns of functional gradients and metabolism (p = 2.47 × 10-8 ). PLS analysis and gene ontological analyses further revealed that genes were mainly enriched for metabolic, catabolic, cellular response to ions, and regulation of DNA transcription and RNA biosynthesis. In conclusion, our study provided genetic pathological mechanism to explain imaging-defined brain functional-metabolic architecture of PD.
Assuntos
Fluordesoxiglucose F18 , Doença de Parkinson , Humanos , Fluordesoxiglucose F18/metabolismo , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Encéfalo/patologia , Neuroimagem , Imageamento por Ressonância Magnética , Expressão GênicaRESUMO
BACKGROUND: Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing. Previous studies have indicated that antler reserve mesenchyme (RM) cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages. AIM: To develop hydrogels from the antler RM matrix (HARM) and evaluate the effect on wound healing. METHODS: We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin. Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application. RESULTS: The results showed that HARM accelerated wound healing rate and reduced scar formation. Also, HARM stimulated the regeneration of cutaneous appendages and blood vessels, and reduced collagen fiber aggregation. Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site. The levels of fetal wound healing-related genes, including Collagen III and TGFß3 treated with HARM were all increased, while the expression levels of Collagen I, TGFß1, and Engrailed 1 were decreased in the healing. Moreover, the number of stem cells was increased in the fetal-like niche created by HARM, which may contribute to the regeneration of cutaneous appendages. CONCLUSION: Overall, we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds. We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing, and thus pave the way for HARM to be developed for the clinic use.