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1.
ACS Omega ; 9(12): 14551-14557, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38559996

RESUMO

In order to improve the energy conversion efficiency and power density of the tritium-powered betavoltaic battery, titanium was deposited on the inner surface of the deep porous three-dimensional structure semiconductor as a tritium absorption material. Therefore, magnetron sputtering technology was used to explore the parameters of titanium coating on the inner surface of a deep porous semiconductor. First, the effects of argon pressure and sputtering power on the properties of titanium films were studied. The properties of the titanium films were characterized by a scanning electron microscope and an atomic force microscope. The optimized sputtering parameters were obtained as follows: argon pressure of 0.5 Pa and sputtering power of 80 W. Based on this parameter, the background vacuum and coating angle were changed, and the titanium film was coated in the deep porous structure. Energy dispersive spectrometry line scan and surface scan were used to analyze the coating results, which showed that these two parameters directly affected the content of titanium in the channel, and the area of titanium in the channel structure accounted for more than 50% under each test condition.

2.
Ann Hematol ; 103(1): 153-162, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37749319

RESUMO

The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).


Assuntos
Hiperplasia do Linfonodo Gigante , Humanos , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/epidemiologia , Hiperplasia do Linfonodo Gigante/terapia , Estudos Retrospectivos , Pequim/epidemiologia , Prognóstico , China/epidemiologia
3.
iScience ; 27(1): 108663, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38155782

RESUMO

Sustainable energy technologies enable solutions for future green transportation. Realizing status awareness and effective wireless monitoring of rail transit infrastructure in dark environments, narrow spaces, and unattended conditions has always been a challenge. This study presents a battery-free vibration-powered force sensing system (VFSS) that integrates structural loading, sensing, and energy harvesting. The proposed VFSS can sense a switching force of up to 4 kN in the high-speed railway turnout section, deliver 6.9 mW of average power over a broad frequency band (ca. 500 Hz) under a vibration amplitude of 0.2 mm, and realize wireless data transmission. Through a cross-scale design from the device to the system, we demonstrate an all-in-one smart component that features stress flow, signal flow, and energy flow, which could highlight the implementation of energy structures in the future.

4.
Cell Rep ; 42(8): 112867, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37494184

RESUMO

The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and intellectual disability (ID). We have recently shown that POGZ maintains mouse embryonic stem cells (ESCs). However, the exact mechanisms remain unclear. Here, we show that POGZ plays an important role in the maintenance of ESCs by silencing Dux and endogenous retroviruses (ERVs). POGZ maintains a silent chromatin state at Dux and ERVs by associating with and recruiting TRIM28 and SETDB1, and its loss leads to decreased levels of H3K9me3/H4K20me3, resulting in up-regulation of 2C transcripts and ESC transition to a 2C-like state. POGZ suppresses different classes of ERVs through direct (IAPEy, the intracisternal A-type particle elements) and indirect regulation (MERVL). Activation of POGZ-bound ERVs is associated with up-regulation of nearby neural disease genes such as Serpina3m. Our findings provide important insights into understanding the disease mechanism caused by POGZ dysfunction.


Assuntos
Transtorno do Espectro Autista , Retrovirus Endógenos , Animais , Camundongos , Transtorno do Espectro Autista/genética , Cromatina , Células-Tronco Embrionárias , Retrovirus Endógenos/genética , Genes cdc , Células-Tronco Embrionárias Murinas
5.
Transplant Proc ; 55(7): 1706-1714, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37385841

RESUMO

BACKGROUND: Diagnosis of acute graft-vs-host disease (aGVHD) based on clinical symptoms and biopsy of involved organ was not satisfactory; reliable plasma biomarkers or their panels would be of great value to increase the sensitivity and specificity for such a fatal complication. METHOD: One hundred two patients who received allogeneic hematopoietic stem cell transplantation in our center were included in this study. Systemic biomarkers of ST2, IP10, IL-2Rα, TNFR1, and organ-specific biomarkers of Elafin, REG-3α, and KRT-18F in plasma were tested by ELISA. The correlation of each biomarker or selected panel of some systemic and organ-specific biomarker with aGVHD was investigated. RESULTS: The level of each systemic biomarker in aGVHD patients was significantly higher than that in patients without aGVHD. Organ-specific biomarker of Elafin, REG-3α, and KRT-18F also had predictive value for aGVHD of skin, gastrointestinal tract, and liver, respectively. Combination of ST2 with one of the 3 organ-specific biomarkers could provide more accurate prediction for aGVHD with skin, gastrointestinal tract, and liver, respectively. CONCLUSIONS: All the biomarkers tested in our study correlated with the severity and clinical course of aGVHD. Combination of each systemic biomarker with organ-specific biomarker could increase the sensitivity and specificity for the diagnosis of aGVHD, whereas ST2 with organ-specific biomarker is more sensitive for the diagnosis of organ-specific aGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Elafina , Proteína 1 Semelhante a Receptor de Interleucina-1 , Biomarcadores , Sensibilidade e Especificidade , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda
6.
Biomater Sci ; 11(15): 5274-5286, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37345831

RESUMO

Neurovascularized bone regeneration remains an enormous challenge in the clinic. Biomaterials mimicking the developmental microenvironment might be promising tools to enhance tissue regeneration. In this study, functionalized hydrogel-microsphere composites are developed to enhance bone regeneration via a recapitulating neurovascularized microenvironment. RGD peptide and the porous structure generated by the degradation of gelatin microspheres (GMs) are beneficial for the proliferation and migration of human mesenchymal stem cells (hMSCs); mesoporous silica nanoparticles (MSNs) promote osteogenic differentiation of hMSCs through the delivery of BFP-1 peptide; the QK peptide from the GMs is sustained-released to recruit endogenous endothelial cells (ECs), and IK19 peptide grafted on the hydrogel guides the neurite outgrowth. The in vivo results show that the hydrogel-microsphere composites not only promote new bone formation, but also facilitate nerve infiltration and angiogenesis. Furthermore, the neurovascularized niche created by this composite stimulated neurite growth through MAPK, PI3K, IL17 and TNF signaling pathways, enabling vascularized bone regeneration. The findings suggest a novel bioengineering approach to guide the construction of neurovascularized bone repair materials, which is beneficial for achieving functional bone regeneration and repair.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Humanos , Osteogênese/fisiologia , Hidrogéis/química , Microesferas , Células Endoteliais , Regeneração Óssea , Peptídeos/química , Crescimento Neuronal
7.
Int Immunopharmacol ; 120: 110299, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37201405

RESUMO

Donor-specific anti-HLA antibody (DSA) is a significant obstacle to successful haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and is associated with poor engraftment rates. DSA strongly positive patients with a mean fluorescence intensity (MFI) over 5000 have a primary poor graft function (PGF) rate of over 60%. Currently, there is no consensus on the desensitization of DSA, and existing strategies are complex and have limited effectiveness. To address this issue, we conducted a retrospective study on 19 patients with strongly positive DSA (MFI over 5000) who underwent haplo-HSCT and were treated with intravenous immunoglobulin (IVIg)-based therapy. We also included 38 baseline-matched patients with DSA-negative as controls. Our findings revealed that the cumulative incidence of engraftment, PGF, graft-versus-host disease (GVHD), virus infection, overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) in the DSA strongly positive group after desensitization were comparable to those in the DSA negative group (P > 0.05). Our multivariable analysis showed that disease remission was a protective factor against PGF (P = 0.005, OR = 0.019, 95% CI 0.001-0.312). Subgroup analysis revealed that the desensitization efficacy was equal regardless of DSA type against HLA-I or II, and MFI value over 5000 or not. In conclusion, we propose a simple and effective DSA desensitization strategy based on immunoglobulin to ensure successful engraftment and improve patient prognosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante Haploidêntico , Humanos , Estudos Retrospectivos , Doadores de Tecidos , Imunoglobulinas Intravenosas/uso terapêutico , Soro Antilinfocitário , Antígenos HLA
8.
Int J Hematol ; 118(2): 231-241, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37247070

RESUMO

Light chain amyloidosis is a plasma cell dyscrasia characterized by deposition of misfolded amyloid fibrils in tissues, leading to multi-organ dysfunction. We retrospectively analyzed 335 patients (median age, 60 years) with systemic light chain amyloidosis in the First Hospital of Peking University from 2011 to 2021. Involved organs were the kidney (92.8%), heart (57.9%), liver (12.8%) and peripheral nervous system (6.3%). Chemotherapy was administered to 55.8% (187/335) of patients, among whom 94.7% received novel agent-based regimens. Hematologic response (≥ very good partial response) was achieved in 63.4% of patients who received chemotherapy. Only 18.2% of patients received autologous hematopoietic stem cell transplant (ASCT). Among transplant-eligible patients, the overall survival of ASCT recipients was better than those who received chemotherapy only. The median overall survival of the patients with light chain amyloidosis was 77.5 months. Estimated glomerular filtration rate and Mayo 2012 stage were independent prognostic factors for overall survival in multivariate analysis. Although the younger age and high ratio of renal involvement might contribute to the favorable prognosis of this cohort, the role of novel agents and ASCT is also discernible. This study will provide a comprehensive perspective on progress in treatment of light chain amyloidosis in China.


Assuntos
Amiloidose , Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , População do Leste Asiático , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Prognóstico , Transplante Autólogo
9.
Biomed Pharmacother ; 163: 114818, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37182513

RESUMO

Our previous studies uncovered the glucose-lowering properties of snow chrysanthemum tea, however, the active ingredients and underlying mechanisms were yet to be uncovered. Flavonoids are the most active and abundant components in snow chrysanthemum tea. In this study, we treated leptin-deficient diabetic ob/ob or high-fat diet (HFD)-induced C57BL/6 J obese mice with or without total flavonoids of snow chrysanthemum (TFSC) for 14 weeks. Results indicated that TFSC ameliorated dyslipidemia and fatty liver, thereby reducing hyperlipidemia. Further mechanism experiments, including RNA-seq and experimental validation, revealed TFSC improved glycolipid metabolism primarily by activating the AMPK/Sirt1/PPARγ pathway. Additionally, by integrating UPLC, network pharmacology, transcriptomics, and experimental validation, we identified two novel hypoglycemic compounds, sulfuretin and leptosidin, in TFSC. Treatment with 12.5 µmol/L sulfuretin obviously stimulated cellular glucose consumption, and sulfuretin (3.125, 6.25 and 12.5 µmol/L) significantly mitigated glucose uptake damage and reliably facilitated glucose consumption in insulin-resistant HepG2 cells. Remarkably, sulfuretin interacted with the ligand-binding pocket of PPARγ via three hydrogen bond interactions with the residues LYS-367, GLN-286 and TYR-477. Furthermore, a concentration of 12.5 µmol/L sulfuretin effectively upregulated the expression of PPARγ, exhibiting a comparable potency to a renowned PPARγ agonist at 20 µmol/L. Taken together, our findings have identified two new hypoglycemic compounds and revealed their mechanisms, which significantly expands people's understanding of the active components in snow chrysanthemum that have hypoglycemic effects.


Assuntos
Chrysanthemum , Hipoglicemiantes , Camundongos , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Simulação de Acoplamento Molecular , Chrysanthemum/química , PPAR gama/genética , PPAR gama/metabolismo , Farmacologia em Rede , Transcriptoma , Camundongos Endogâmicos C57BL , Glucose , Flavonoides/farmacologia , Chá
10.
Mol Ther Methods Clin Dev ; 28: 238-248, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36618106

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, has been shown to infect a wide range of animal species, especially mammals, and besides human-to-human transmission, human-to-animal transmission has also been observed in some wild animals and pets, especially in cats. It has been demonstrated that cats are permissive to COVID-19 and are susceptible to airborne infections. Given the high transmissibility potential of SARS-CoV-2 to different host species and the close contact between humans and animals, it is crucial to find mechanisms to prevent the transmission chain and reduce the risk of spillover to susceptible species. Here, we show results from a clinical trial conducted in domestic cats to assess safety and immunogenicity of a linear DNA (linDNA) vaccine encoding the receptor-binding domain (RBD) from SARS-CoV-2 (Lin-COVID-eVax). Lin-COVID-eVax proved to be safe, with no significant adverse events, and was able to elicit both RBD-specific antibodies and T cells. Also, the linDNA vaccine induced neutralizing antibody titers against ancestral SARS-CoV-2 virus and its variants. These findings demonstrate the safety and immunogenicity of a genetic vaccine against COVID-19 administered to cats and strongly support the development of vaccines for preventing viral spread in susceptible species, especially those in close contact with humans.

11.
Zool Res ; 44(2): 259-268, 2023 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-36650065

RESUMO

Reproductive strategies and spawning habits play key roles in the evolution of endemic East Asian cyprinids. However, the molecular mechanisms underlying the regulation of spawning habits are not well understood. We recently identified zona pellucida (Zp) as the top differentially expressed protein between East Asian cyprinids that produce adhesive and semi-buoyant eggs, suggesting that Zp protein may play important roles in the regulation of egg type. In this work, we generated transgenic zebrafish in which oocyte-specific expression of zp genes from rare minnow ( Gobiocypris rarus), an East Asian cyprinid laying adhesive eggs, was driven by a zebrafish zp3.2 gene promoter. We found that the transgenic eggs obtained partial adhesiveness and exhibited alteration in hydration and buoyancy. Abnormal metabolism of vitellogenin (VTG) may contribute to enhanced hydration and/or buoyancy. Our work shows that expression of the exogenous zp3a gene from an adhesive-egg producing fish is sufficient to induce changes in both egg adhesiveness and buoyancy in zebrafish, emphasizing the important role of zp genes in the regulation of spawning habits. Our results thus provide new insights into how endemic East Asian cyprinids may have adapted to the Yangtze river-lake system via changes in spawning habits.


Assuntos
Cyprinidae , Peixe-Zebra , Animais , Peixe-Zebra/genética , Glicoproteínas da Zona Pelúcida/genética , Glicoproteínas da Zona Pelúcida/metabolismo , Proteínas do Ovo/genética , Proteínas do Ovo/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Sequência de Aminoácidos , Adesividade , Receptores de Superfície Celular/genética , Animais Geneticamente Modificados/genética
12.
Int J Mol Sci ; 25(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38203595

RESUMO

Long interspersed element-1 (LINE-1; L1s) are mobile genetic elements that comprise nearly 20% of the human genome. L1s have been shown to have important functions in various biological processes, and their dysfunction is thought to be linked with diseases and cancers. However, the roles of the repetitive elements are largely not understood. While the CRISPR activation (CRISPRa) system based on catalytically deadCas9 (dCas9) is widely used for genome-wide interrogation of gene function and genetic interaction, few studies have been conducted on L1s. Here, we report using the CRISPRa method to efficiently activate L1s in human L02 cells, a derivative of the HeLa cancer cell line. After CRISPRa, the young L1 subfamilies such as L1HS/L1PA1 and L1PA2 are found to be expressed at higher levels than the older L1s. The L1s with high levels of transcription are closer to full-length and are more densely occupied by the YY1 transcription factor. The activated L1s can either be mis-spliced to form chimeric transcripts or act as alternative promoters or enhancers to facilitate the expression of neighboring genes. The method described here can be used for studying the functional roles of young L1s in cultured cells of interest.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Elementos Nucleotídeos Longos e Dispersos , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Genoma Humano , Células HeLa , Regiões Promotoras Genéticas
13.
Front Neurosci ; 16: 960149, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117635

RESUMO

The development of central nervous system (CNS) and enteric nervous system (ENS) is under precise and strict control in vertebrates. Whether and how the Polycomb repressive complex 1 (PRC1) is involved in it remain unclear. To investigate the role of PRC1 in the nervous system development, using CRISPR/Cas9 technology, we have generated mutant zebrafish lines for the rnf2 gene which encodes Ring1b, the enzymatic component of the PRC1 complex. We show that rnf2 loss of function leads to abnormal migration and differentiation of neural crest and neural precursor cells. rnf2 mutant embryos exhibit aganglionosis, in which the hindgut is devoid of neurons. In particular, the formation of 5-HT serotonin neurons and myelinating glial cells is defective. Furthermore, ectopic expression of ENS marker genes is observed in forebrain of rnf2 mutant embryos. These findings suggest that the rnf2 gene plays an important role in the migration and differentiation of neural precursor cells, and its absence leads to abnormal development of ENS and CNS in zebrafish.

14.
Front Immunol ; 13: 927804, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967402

RESUMO

Multiple myeloma (MM) is a malignant plasma cell disorder affecting mainly the elderly population. Revolutionary progress in immunotherapy has been made recently, including monoclonal antibodies and chimeric antigen receptor T cell (CAR-T) therapies; however, the high relapse rate remains problematic. Therefore, combination therapies against different targets would be a reasonable strategy. In this study, we present a new X-chromosome encoded testis-cancer antigen (CTA) AKAP4 as a potential target for MM. AKAP4 is expressed in MM cell lines and MM primary malignant plasma cells. HLA-A*0201-restricted cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) transduced with an adenovirus vector encoding the full-length AKAP4 gene were demonstrated to lyse AKAP4+ myeloma cells. Seven of the 12 candidate epitopes predicated by the BIMAS and SYFPEITH algorithms were able to bind HLA-A*0201 in the T2 binding assay, of which only two peptides were able to induce CTL cytotoxicity in the co-culture of peptide-loaded human mature dendritic cells and the autologous peripheral blood mononuclear cells (PBMCs) from the same HLA-A*0201 donor. The AKAP4 630-638 VLMLIQKLL was identified as the strongest CTL epitope by the human IFN-γ ELISPOT assay. Finally, the VLMLIQKLL-specific CTLs can lyse the HLA-A*0201+AKAP4+ myeloma cell line U266 in vitro, and inhibit tumor growth in the mice bearing U266 tumors in vivo. These results suggest that the VLMLIQKLL epitope could be used to develop cancer vaccine or T-cell receptor transgenic T cells (TCR-T) to kill myeloma cells.


Assuntos
Proteínas de Ancoragem à Quinase A , Linfócitos T CD8-Positivos , Epitopos de Linfócito T , Mieloma Múltiplo , Proteínas de Ancoragem à Quinase A/genética , Proteínas de Ancoragem à Quinase A/imunologia , Idoso , Animais , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Antígeno HLA-A2/genética , Antígeno HLA-A2/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Camundongos , Mieloma Múltiplo/genética , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Peptídeos
15.
J Clin Med ; 11(16)2022 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-36013154

RESUMO

Primary EBV-positive mucocutaneous ulcer (EBVMCU) is a rare and indolent disorder occurring in the oropharynx, skin, and gastrointestinal tract, with remission after removal of the immunosuppressive causes. We present a 69-year-old woman with heartburn, regurgitation of gastric acid, enlarged lymph nodes, and parotid glands. The endoscopic examination showed a circumscribed ulcer in the lower esophagus. A biopsy pathology indicated an esophageal EBV-associated lymphoproliferative disorder and a parotid gland/lymph node indolent B-cell lymphoma. Interestingly, the patient did not undergo any treatment, but the endoscopic ulcer improved significantly after more than 2 months. The last pathology showed EBV negativity, and EBVMCU was considered in combination with clinical and endoscopic manifestations. We followed up with the patient at 6 months, and the symptoms of acid reflux and heartburn had disappeared. Our case demonstrates that EBVMCU may occur in the esophagus with spontaneous regression.

16.
Mol Autism ; 13(1): 24, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650610

RESUMO

BACKGROUND: The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its roles in embryonic stem cells (ESCs), neural development and diseases. METHODS: We generated Pogz-/- ESCs and directed ESC differentiation toward a neural fate. We performed biochemistry, ChIP-seq, ATAC-seq, and bioinformatics analyses to understand the role of POGZ. RESULTS: We show that POGZ is required for the maintenance of ESC identity and the up-regulation of neural genes during ESC differentiation toward a neural fate. Genome-wide binding analysis shows that POGZ is primarily localized to gene promoter and enhancer regions. POGZ functions as both a transcriptional activator and repressor, and its loss leads to deregulation of differentiation genes, including neural genes. POGZ physically associates with the SWI-SNF (esBAF) chromatin remodeler complex, and together they modulate enhancer activities via epigenetic modifications such as chromatin remodeling and histone modification. During ESC neural induction, POGZ-mediated recruitment of esBAF/BRG1 and H3K27ac are important for proper expression of neural progenitor genes. LIMITATIONS: The genotype and allele relevant to human neurodevelopmental disorders is heterozygous loss of function. This work is designed to study the effects of loss of POGZ function on ESCs and during ESC neural induction. Also, this work lacks of in vivo validation using animal models. CONCLUSIONS: The data suggest that POGZ is both a transcription factor and a genome regulator, and its loss leads to defects in neural induction and neurogenesis.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Animais , Transtorno do Espectro Autista/genética , Diferenciação Celular , Desenvolvimento Embrionário , Células-Tronco Embrionárias/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
J Exp Clin Cancer Res ; 41(1): 195, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668533

RESUMO

BACKGROUND: DNA-based vaccines represent a simple, safe and promising strategy for harnessing the immune system to fight infectious diseases as well as various forms of cancer and thus are considered an important tool in the cancer immunotherapy toolbox. Nonetheless, the manufacture of plasmid DNA vaccines has several drawbacks, including long lead times and the need to remove impurities from bacterial cultures. Here we report the development of polymerase chain reaction (PCR)-produced amplicon expression vectors as DNA vaccines and their in vivo application to elicit antigen-specific immune responses in animal cancer models. METHODS: Plasmid DNA and amplicon expression was assessed both in vitro, by Hela cells transfection, and in vivo, by evaluating luciferase expression in wild-type mice through optical imaging. Immunogenicity induced by DNA amplicons was assessed by vaccinating wild-type mice against a tumor-associated antigen, whereas the antitumoral effect of DNA amplicons was evaluated in a murine cancer model in combination with immune-checkpoint inhibitors (ICIs). RESULTS: Amplicons encoding tumor-associated-antigens, such as telomerase reverse transcriptase or neoantigens expressed by murine tumor cell lines, were able to elicit antigen-specific immune responses and proved to significantly impact tumor growth when administered in combination with ICIs. CONCLUSIONS: These results strongly support the further exploration of the use of PCR-based amplicons as an innovative immunotherapeutic approach to cancer treatment.


Assuntos
Vacinas Anticâncer , Neoplasias , Vacinas de DNA , Animais , Antígenos de Neoplasias , DNA , Células HeLa , Humanos , Imunoterapia/métodos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/terapia
18.
Int J Mol Sci ; 23(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35682541

RESUMO

Germline stem cells (GSCs) are a group of unique adult stem cells in gonads that act as important transmitters for genetic information. Donor GSCs have been used to produce offspring by transplantation in fisheries. In this study, we successfully isolated and enriched GSCs from the ovary, ovotestis, and testis of Monopterus albus, one of the most important breeding freshwater fishes in China. Transcriptome comparison assay suggests that a distinct molecular signature exists in each type of GSC, and that different signaling activities are required for the maintenance of distinct GSCs. Functional analysis shows that fGSCs can successfully colonize and contribute to the germline cell lineage of a host zebrafish gonad after transplantation. Finally, we describe a simple feeder-free method for the isolation and enrichment of GSCs that can contribute to the germline cell lineage of zebrafish embryos and generate the germline chimeras after transplantation.


Assuntos
Células-Tronco Adultas , Peixe-Zebra , Animais , Feminino , Células Germinativas , Gônadas , Masculino , Processos de Determinação Sexual , Peixe-Zebra/genética
19.
Adv Sci (Weinh) ; 9(18): e2200670, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35478383

RESUMO

Natural tissues are composed of ordered architectural organizations of multiple tissue cells. The spatial distribution of cells is crucial for directing cellular behavior and maintaining tissue homeostasis and function. Herein, an artificial bone bioceramic scaffold with star-, Tai Chi-, or interlacing-shaped multicellular patterns is constructed. The "cross-talk" between mesenchymal stem cells (MSCs) and macrophages can be effectively manipulated by altering the spatial distribution of two kinds of cells in the scaffolds, thus achieving controllable modulation of the scaffold-mediated osteo-immune responses. Compared with other multicellular patterns, the Tai Chi pattern with a 2:1 ratio of MSCs to macrophages is more effective in activating anti-inflammatory M2 macrophages, improving MSCs osteogenic differentiation, and accelerating new bone formation in vivo. In brief, the Tai Chi pattern generates a more favorable osteo-immune environment for bone regeneration, exhibiting enhanced immunomodulation and osteogenesis, which may be associated with the activation of BMP-Smad, Oncostatin M (OSM), and Wnt/ß-catenin signaling pathways in MSCs mediated by macrophage-derived paracrine signaling mediators. The study suggests that the manipulation of cell distribution to improve tissue formation is a feasible approach that can offer new insights for the design of tissue-engineered bone substitutes with multicellular interactions.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Materiais Biocompatíveis , Regeneração Óssea , Diferenciação Celular , Osteogênese/fisiologia
20.
Molecules ; 26(23)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34885771

RESUMO

Sea buckthorn berries are rich in bioactive compounds and can be used for medicine and food. The variety and drying method used have an important influence on quality. In this study, different sea buckthorn varieties from China were selected and dried with four common drying methods. The total phenolic content (TPC), total flavonoids content (TFC), contents of 12 phenolic compounds and antioxidant capacity in vitro were analyzed. The results showed that the TPC, TFC and antioxidant activity of two wild sea buckthorn berries were higher than those of three cultivated berries, and for the same varieties, measured chemical contents and antioxidant activity of the freeze-dried fruit were significantly higher than those obtained with three conventional drying methods. In addition, forty-one compounds in sea buckthorn berry were identified by UPLC-PDA-Q/TOF-MS, most of which were isorhamnetin derivatives. Multivariate statistical analysis revealed narcissin and isorhamnetin-3-O-glucoside varied significantly in sea buckthorn berries of different varieties and with different drying methods; they were potential quality markers. Strong correlations were found between TPC, gallic acid and antioxidant capacity (p < 0.05). The results revealed how components and antioxidant activity varied in different sea buckthorn, which provides a valuable reference for quality control and further development and utilization of sea buckthorn.


Assuntos
Antioxidantes/química , Flavonoides/química , Hippophae/química , Fenóis/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Flavonoides/isolamento & purificação , Liofilização , Frutas/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Folhas de Planta/química
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