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1.
Anal Methods ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39036899

RESUMO

In recent years, the cargo profiles of extracellular vesicles (EVs), which were inherited from their parent cells, have emerged as a reliable biomarker for liquid biopsy (LB) in disease diagnosis, prognosis, and treatment monitoring. EVs secreted by different cells exhibit distinct characteristics, particularly in terms of disease diagnosis and prediction. However, currently available techniques for the quantitative analysis of EV cargoes, including enzyme-linked immunosorbent assay (ELISA), cannot specifically identify the cellular origin of EVs, thus seriously affecting the accuracy of EV-based liquid biopsy. In light of this, we here developed ultrabright fluorescent nanosphere (FNs)-based test strips which have the unique capability to specifically assess the levels of PD-L1-positive EVs (PD-L1+ EVs) derived from both tumor cells and immune cells in bodily fluids. The levels of PD-L1+ EV subpopulations in human saliva were quantified using the ultrabright fluorescent nanosphere-based test strips with more convenience and higher efficiency (detection time <30 min). Results demonstrated that the fluorescence intensity of the test line exhibited a good linear relationship respectively with the PD-L1 levels of tumor cell- (R2 = 0.993) and immune cell-derived EVs (R2 = 0.982) in human saliva. By assessing the levels of PD-L1+ EV subpopulations, our test strips hold immense potential for advancing the application of PD-L1+ EV subpopulation-based predictions in tumor diagnosis and prognosis evaluation. In summary, by integrating the benefits of FNs and lateral flow chromatography, we here provide a strategy to accurately measure the cargo levels of EVs originating from diverse cell sources in bodily fluids.

2.
Aging (Albany NY) ; 16(13): 10841-10859, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38967635

RESUMO

Previous studies have reported the correlation between gut microbiota (GM), GM-derived metabolites, and various intestinal and extra-intestinal cancers. However, limited studies have investigated the correlation between GM, GM-derived metabolites, and osteosarcoma (OS). This study successfully established a female BALB/c nude mouse model of OS. Mice (n = 14) were divided into the following two groups (n = 7/group): OS group named OG, injected with Saos-2 OS cells; normal control group named NCG, injected with Matrigel. The GM composition and metabolites were characterized using 16S rDNA sequencing and untargeted metabolomics, respectively. Bioinformatics analysis revealed that amino acid metabolism was dysregulated in OS. The abundances of bone metabolism-related genera Alloprevotella, Rikenellaceae_RC9_gut_group, and Muribaculum were correlated with amino acid metabolism, especially histidine metabolism. These findings suggest the correlation between GM, GM-derived metabolites, and OS pathogenesis. Clinical significance: The currently used standard therapeutic strategies for OS, including surgery, chemotherapy, and radiation, are not efficacious. The findings of this study provided novel insights for developing therapeutic, diagnostic, and prognostic strategies for OS.


Assuntos
Fezes , Microbioma Gastrointestinal , Metaboloma , Camundongos Endogâmicos BALB C , Osteossarcoma , Animais , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Feminino , Camundongos , Fezes/microbiologia , Neoplasias Ósseas/metabolismo , Modelos Animais de Doenças , Camundongos Nus , Humanos , Linhagem Celular Tumoral , Metabolômica/métodos , Aminoácidos/metabolismo
3.
J Natl Compr Canc Netw ; : 1-5, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39074504

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the few cancers for which screening has been associated with better survival and morbidity, but screening uptake has been underexplored in spouses of existing patients with CRC. The objective of this study was to evaluate whether a brief, structured behavioral intervention delivered to spouses of patients with CRC in a colorectal clinical setting could increase fecal immunochemical test (FIT) uptake within 3 months of the study period. METHODS: This study was designed as a block randomized, unblinded, parallel trial conducted in the colorectal outpatient clinics of 2 public tertiary hospitals in Singapore from December 2017 to February 2023. The intervention group received a structured informational pamphlet on CRC screening by the Singapore Ministry of Health and a printed guide with instructions on how to properly use a FIT kit. RESULTS: No significant differences in baseline characteristics were observed between the 2 groups. There was a statistically significant difference (P<.001) in FIT screening uptake between spouses in each group, with 86.2% (n=25) in the intervention group and 38.7% (n=12) in the control group. CONCLUSIONS: Our study demonstrated that a brief, structured behavioral intervention offered to spouses accompanying patients with CRC while they wait for the clinic appointment is useful in increasing FIT screening uptake rates. Colorectal clinics can consider setting aside 10 to 15 minutes to educate accompanying spouses in the future as a complementary avenue to holistically promote CRC prevention, subjected to the resources available in each clinic. CLINICALTRIALS: gov identifier: NCT04544852.

4.
Medicine (Baltimore) ; 103(26): e38618, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941435

RESUMO

RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy. PATIENT CONCERNS: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension. DIAGNOSES: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy. INTERVENTIONS: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause. OUTCOMES: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm. LESSONS: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.


Assuntos
Microangiopatias Trombóticas , Humanos , Feminino , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/diagnóstico , Pessoa de Meia-Idade , Evolução Fatal , Hipertensão Pulmonar/etiologia , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico
6.
Heliyon ; 10(8): e29275, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38699747

RESUMO

Background: The clinical significance of immune-related antigen CD58 in gliomas remains uncertain. The aim of this study was to examine the clinical importance and possible core related genes of CD58 in gliomas. Methods: Pan-cancer analysis was to observe the association between CD58 and different tumors, glioma RNA sequencing data and clinical sample analyses were used to observe the relationship between CD58 and glioma, shRNA interference models were to observe the impact of CD58 on glioma cell function, and four glioma datasets and two online analysis platforms were used to explore the core related genes affecting the correlation between CD58 and glioma. Results: High CD58 expression was associated with worse prognosis in various tumors and higher malignancy in glioma. Down regulation of CD58 expression was linked to decreased proliferation, increased apoptosis, and reduced metastasis in glioma cells. The pathways involved in CD58-related effects were enriched for immune cell adhesion and immune factor activation, and the core genes were CASP1, CCL2, IL18, MYD88, PTPRC, and TLR2. The signature of CD58 and its core-related genes showed superior predictive power for glioma prognosis. Conclusion: High CD58 expression is correlated with more malignant glioma types, and also an independent risk factor for mortality in glioma. CD58 and its core-related genes may serve as novel biomarkers for diagnosing and treating glioma.

7.
Heliyon ; 10(10): e30889, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38770292

RESUMO

Breast cancer is the most common cause of female morbidity and death worldwide. Compared with other cancers, early detection of breast cancer is more helpful to improve the prognosis of patients. In order to achieve early diagnosis and treatment, clinical treatment requires rapid and accurate diagnosis. Therefore, the development of an automatic detection system for breast cancer suitable for patient imaging is of great significance for assisting clinical treatment. Accurate classification of pathological images plays a key role in computer-aided medical diagnosis and prognosis. However, in the automatic recognition and classification methods of breast cancer pathological images, the scale information, the loss of image information caused by insufficient feature fusion, and the enormous structure of the model may lead to inaccurate or inefficient classification. To minimize the impact, we proposed a lightweight PCSAM-ResCBAM model based on two-stage convolutional neural network. The model included a Parallel Convolution Scale Attention Module network (PCSAM-Net) and a Residual Convolutional Block Attention Module network (ResCBAM-Net). The first-level convolutional network was built through a 4-layer PCSAM module to achieve prediction and classification of patches extracted from images. To optimize the network's ability to represent global features of images, we proposed a tiled feature fusion method to fuse patch features from the same image, and proposed a residual convolutional attention module. Based on the above, the second-level convolutional network was constructed to achieve predictive classification of images. We evaluated the performance of our proposed model on the ICIAR2018 dataset and the BreakHis dataset, respectively. Furthermore, through model ablation studies, we found that scale attention and dilated convolution play an important role in improving model performance. Our proposed model outperforms the existing state-of-the-art models on 200 × and 400 × magnification datasets with a maximum accuracy of 98.74 %.

8.
BMC Musculoskelet Disord ; 25(1): 290, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622692

RESUMO

BACKGROUND: The proximal femoral nail anti-rotation (PFNA) with cement enhancement enhances the anchorage ability of internal fixation in elderly with osteoporotic intertrochanteric fracture. However, whether it is superior to hemiarthroplasty is still controversial. The present study aimed to determine which treatment has better clinical outcomes among older patients. METHODS: We retrospectively analyzed 102 elderly patients with osteoporosis who developed intertrochanteric fractures and underwent PFNA combined with cement-enhanced internal fixation (n = 52, CE group), and hemiarthroplasty (n = 50, HA group) from September 2012 to October 2018. All the intertrochanteric fractures were classified according to the AO/OTA classification. Additionally, the operative time, intraoperative blood loss, intraoperative and postoperative blood transfusion rates, postoperative weight-bearing time, hospitalization time, Barthel Index of Activities Daily Living, Harris score of hip function, visual analog (VAS) pain score, and postoperative complications were compared between the two groups. RESULTS: The CE group had significantly shorter operative time, lesser intraoperative blood loss, lower blood transfusion rate, and longer postoperative weight-bearing time than the HA group. The CE group had lower Barthel's Index of Activities of Daily Living, lower Harris' score, and higher VAS scores in the first and third months after surgery than the HA group, but no difference was observed between the two groups from 6 months to 12 months. There was no significant difference in the total post-operative complications between the two groups. CONCLUSION: The use of PFNA combined with a cement-enhanced internal fixation technique led to shorter operative time and lesser intraoperative blood loss and trauma in elderly patients as compared to HA.


Assuntos
Fixação Intramedular de Fraturas , Hemiartroplastia , Fraturas do Quadril , Humanos , Idoso , Estudos Retrospectivos , Pinos Ortopédicos , Hemiartroplastia/efeitos adversos , Hemiartroplastia/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Atividades Cotidianas , Resultado do Tratamento , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Cimentos Ósseos/uso terapêutico , Complicações Pós-Operatórias/cirurgia , Fixação Intramedular de Fraturas/efeitos adversos
9.
Cell Death Discov ; 10(1): 193, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664375

RESUMO

Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.

10.
Aging (Albany NY) ; 16(2): 1336-1351, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38231481

RESUMO

The gut microbiota is closely associated with tumor progression and treatment in a variety of cancers. However, the alteration of the gut microbiota during the progression and chemotherapy of osteosarcoma remains poorly understood. This study aimed to explore the relationship between dysbiosis in the gut microbiota during osteosarcoma growth and chemotherapy treatment. We used BALB/c nude mice to establish osteosarcoma xenograft tumor models and administered cisplatin (CDDP) or doxorubicin (DOX) intraperitonially once every 2 days for a total of 5 times to establish effective chemotherapy models. Fecal samples were collected and processed for 16S rRNA sequencing to analyze the composition of the gut microbiota. We observed that the abundances of Colidextribacter, Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG-010, Lachnospiraceae_UCG-006, and Lachnoclostridium decreased, and the abundances of Alloprevotella and Enterorhabdus increased in the osteosarcoma mouse model group compared to those in the control group. In addition, genera, such as Lachnoclostridium and Faecalibacterium were more abundant in chemotherapy-treated mice than those in saline-treated mice. Additionally, we observed that alterations in some genera, including Lachnoclostridium and Colidextribacter in the osteosarcoma animal model group returned to normal after CDDP or DOX treatment. Furthermore, the function of the gut microbiota was inferred through PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), which indicated that metabolism-related microbiota was highly enriched and significantly different in each group. These results indicate correlations between dysbiosis of the gut microbiota and osteosarcoma growth and chemotherapy treatment with CDDP or DOX and may provide novel avenues for the development of potential adjuvant therapies.


Assuntos
Neoplasias Ósseas , Microbioma Gastrointestinal , Osteossarcoma , Humanos , Camundongos , Animais , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Microbioma Gastrointestinal/genética , Disbiose/microbiologia , RNA Ribossômico 16S/genética , Camundongos Nus , Filogenia , Doxorrubicina/uso terapêutico , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico
12.
Mikrochim Acta ; 190(12): 462, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945912

RESUMO

Fluorescent lateral flow immunoassay (LFA), one tool in point of care testing (POCT) systems for breast cancer, has attracted attention because it is quick, simple, and convenient. However, samples and the constituent material exhibit autofluorescence in the visible region, which is a very large obstacle in the development of fluorescent LFAs. The autofluorescence of biological samples is scarcely found in the second near-infrared (NIR-II) range and samples scatter and absorb less NIR-II light than visible light. Here, we report an NIR-II QD-LFA platform using the NIR-II fluorescent Ag2Se quantum dots (QDs) with 1020 nm emission encapsulated into polystyrene beads as fluorescent probes. The NIR-II LFA platform was established to detect breast cancer tumour markers (CEA and CA153) within 15 min with a low limit of detection (CEA: 0.768 ng mL-1, CA153: 1.192 U mL-1), high recoveries (93.7% ~ 108.8%), and relative standard deviations (RSDs) of less than 10%. This study demonstrated the potential of NIR-II Ag2Se polystyrene beads as a fluorescent probe in LFA for rapid and accurate identification of biomarkers. They are suited for use in professional situations.


Assuntos
Neoplasias , Poliestirenos , Biomarcadores Tumorais , Corantes Fluorescentes , Imunoensaio , Luz
13.
J Adv Res ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38036217

RESUMO

INTRODUCTION: Neurological dysfunction induced by fluoride contamination is still one of major concern worldwide. Recently, neuroprotective roles of silent information regulator 1 (SIRT1) focusing on mitochondrial function have been highlighted. However, what roles SIRT1 exerts and the underlying regulative mechanisms, remain largely uncharacterized in such neurotoxic process of fluoride. OBJECTIVES: We aimed at evaluating the regulatory roles of SIRT1 in human neuroblastoma SH-SY5Y cells and Sprague-Dawley rats with fluoride treatment, and to further identify potential miRNA directly targeting SIRT1. METHODS: Pharmacological suppression of SIRT1 by nicotinamide (NIC) and promotion of SIRT1 by adenovirus (Ad-SIRT1) or resveratrol (RSV) were employed to assess the effects of SIRT1 in mitochondrial dysfunction induced by fluoride. Also, miRNAs profiling and bioinformatic prediction were used to screen the miRNAs which can regulate SIRT1 directly. Further, chemical mimic or inhibitor of chosen miRNA was applied to validate the modulation of chosen miRNA. RESULTS: NIC exacerbated defects in mitochondrial network dynamics and cytochrome c (Cyto C) release-driven apoptosis, contributing to fluoride-induced neuronal death. In contrast, the ameliorative effects were observed when overexpressing SIRT1 by Ad-SIRT1 in vitro or RSV in vivo. More importantly, miR-708-3p targeting SIRT1 directly was identified. And interestingly, moreover, treatment with chemically modified miR-708-3p mimic aggravated, while miR-708-3p inhibitor suppressed fluoride-caused neuronal death. Further confirmedly, overexpressing SIRT1 effectively neutralized miR-708-3p mimic-worsened fluoride neuronal death via correcting mitochondrial network dynamics. On contrary, inhibiting SIRT1 counteracted the promotive effects of miR-708-3p inhibitor against neurotoxic response by fluoride through aggravating abnormal mitochondrial network dynamics. CONCLUSION: These data underscore the functional importance of SIRT1 to mitochondrial network dynamics in neurotoxic process of fluoride and further screen a novel unreported neuronal function of miR-708-3p as an upstream regulator of targeting SIRT1, which has important theoretical implications for a potential therapeutic and preventative target for treatment of neurotoxic progression by fluoride.

14.
Curr Med Sci ; 43(6): 1061-1065, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37924387

RESUMO

Long COVID symptoms typically occur within 3 months of an initial COVID-19 infection, last for more than 2 months, and cannot be explained by other diagnoses. The most common symptoms include fatigue, dyspnea, coughing, and cognitive impairment. The mechanisms of long COVID are not fully understood, but several hypotheses have been put forth. These include coagulation and fibrosis pathway activation, inflammatory and autoimmune manifestations, persistent virus presence, and Epstein-Barr virus reactivation. Hyperbaric oxygen therapy (HBOT) is a therapeutic method in which a person inhales 100% oxygen under pressure greater than that of the atmosphere. HBOT has some therapeutic effects, including improvement of microcirculation, inhibition of cytokine release leading to a reduction in inflammatory responses, inhibition of autoimmune responses, and promotion of neurological repair. Several clinical trials have been carried out using HBOT to treat long COVID. The results suggest that HBOT helps to improve symptom severity, reduce symptom duration, and enhance patients' quality of life. It is believed that HBOT is an effective option for patients with long COVID, which is worth actively promoting.


Assuntos
COVID-19 , Infecções por Vírus Epstein-Barr , Oxigenoterapia Hiperbárica , Humanos , Oxigenoterapia Hiperbárica/métodos , Oxigênio , Síndrome de COVID-19 Pós-Aguda , Qualidade de Vida , COVID-19/terapia , Herpesvirus Humano 4
15.
Open Life Sci ; 18(1): 20220736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37791064

RESUMO

The presented case report describes an incredibly rare instance of an intramedullary bronchial cyst located in the thoracic spinal canal on the dorsal side of the spinal cord, which was observed in a patient with chronic myelogenous leukemia. A 29-year-old man presented with back pain for half a month, along with numbness and pain below the chest and ribs for 1 week. Hypersensitivity was present in the inferior plane of the long xiphoid process in the nervous system. Magnetic resonance imaging (MRI) showed intramedullary cystic lesions in the vertebral body plane of the third to the fourth thoracic vertebra. There was no recurrence during the 6-month postoperative follow-up period. The histopathological findings were consistent with bronchogenic cysts. Cystic lesions were eliminated through the posterior median approach. After the cyst ruptured during surgery, gel liquid was seen, and the majority of the cyst walls were removed. One week after the surgery, the hypersensitivity fully subsided. Six months following surgery, an updated MRI revealed no recurrence. Intramedullary bronchogenic cysts on the dorsal side of the thoracic spine are extremely uncommon. Diagnosis requires histopathological evidence, and it is challenging to diagnose before surgery. Prompt surgical resection is recommended in case of positive diagnosis.

16.
World Neurosurg ; 178: e777-e790, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37562682

RESUMO

OBJECTIVE: The anterior clinoid process (ACP) is surrounded by nerves and vessels that, together, constitute an intricate anatomical structure with variations that challenges the performance of individualized anterior clinoidectomy in treating lesions with different extents of invasion. In the present study, we established a 6-surface system for the ACP based on anatomical landmarks and analyzed its value in guiding ACP drilling and resection of paraclinoid meningiomas. METHODS: Using the anatomical characteristics of 10 dry skull specimens, we set 9 anatomical landmarks to delineate the ACP into 6 surfaces. Guided by our 6-surface system and eggshell technique, 5 colored silicone-injected anatomical specimens were dissected via a frontotemporal craniotomy to perform anterior clinoidectomy. Next, 3 typical cases of paraclinoid meningioma were selected to determine the value of using our 6-surface system in tumor resection. RESULTS: Nine points (A-H and T) were proposed to delineate the ACP surface into frontal, temporal, optic nerve, internal carotid artery, cranial nerve III, and optic strut surfaces according to the adjacent tissues. Either intradurally or extradurally, the frontal and temporal surfaces could be identified and drilled into depth, followed by skeletonization of the optic nerve, cranial nerve III, internal carotid artery, and optic strut surfaces. After the residual bone was removed, the ACP was drilled off. In surgery of paraclinoid meningiomas, our 6-surface system provided great benefit in locating the dura, nerves, and vessels, thus, increasing the safety of opening the optic canal and relaxing the oculomotor or optic nerves and allowing for individualized ACP drilling for meningioma removal. CONCLUSIONS: Our 6-surface system adds much anatomical information to the classic Dolenc triangle and can help neurosurgeons, especially junior ones, to increase their understanding of the paraclinoid spatial structure and accomplish individualized surgical procedures with high safety and minimal invasiveness.


Assuntos
Aneurisma Intracraniano , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Aneurisma Intracraniano/cirurgia , Base do Crânio/cirurgia , Osso Esfenoide/cirurgia , Osso Esfenoide/anatomia & histologia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia
17.
Yi Chuan ; 45(1): 42-51, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36927637

RESUMO

The optimal diagnosis and treatment of pediatric diseases depend on more adequate understanding of pathophysiology. The advent of induced pluripotent stem cells (iPSCs) has provided new strategies for the research and therapy of pediatric diseases. iPSCs are pluripotent stem cells induced by reprogramming of mature cells. Now they can be induced from many types of somatic cells (such as fibroblasts, peripheral blood mononuclear cells and urine cells).With the improvement of various reprogramming methods, its generation procedure is more and more optimized, and the use of small molecules to induce iPSCs is one of the research focus now. Due to their ability to differentiate into a variety of cells, combined with the development of gene editing technology, iPSCs have been increasingly favored in the modeling of diseases and cell therapy, especially hereditary diseases, and have achieved some success in clinical treatment. But before they can be widely used in clinical treatment, there are still some problems to be solved, such as tumorigenicity, immunogenicity and heterogeneity. This article reviewed the source of iPSCs, reprogramming technology, applications of iPSCs in common childhood diseases, current problems and prospects, in order to deepen the understanding of iPSCs and provide reference for in-depth research in field of exploring mechanisms of diseases and therapy of diseases.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Criança , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Leucócitos Mononucleares , Fibroblastos , Edição de Genes , Reprogramação Celular/genética , Diferenciação Celular
18.
BMC Med Genomics ; 15(1): 265, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36536381

RESUMO

BACKGROUND: Recently, increasing attention has been drawn to the impact of the tumor microenvironment (TME) on the occurrence and progression of malignant tumors. A variety of 3D culture techniques have been used to simulate TME in vitro. The purpose of this study was to reveal the differences in transcriptional and metabolic levels between osteosarcoma (OS) 2D cells, 3D cells, 3D cell-printed tissue, isolated tissue, and transplanted tumor tissue in vivo. METHODS: We cultured the OS Saos-2 cell line under different culture methods as 2D cells, 3D cells, 3D cell-printed tissue and isolated tissue for 14 days and transplanted tumors in vivo as a control group. Through transcriptomic and metabonomic analyses, we determined the changes in gene expression and metabolites in OS tissues under different culture methods. RESULTS: At the transcriptional level, 166 differentially expressed genes were found, including the SMAD family, ID family, BMP family and other related genes, and they were enriched in the TGF-ß signaling pathway, complement and coagulation cascades, signaling pathways regulating pluripotency of stem cells, Hippo signaling pathway, ferroptosis, cGMP-PKG signaling pathway and other pathways. At the metabolic level, 362 metabolites were significantly changed and enriched in metabolic pathways such as the Fc Epsilon RI signaling pathway, histidine metabolism, primary bile acid biosynthesis, steroid biosynthesis, protein digestion and absorption, ferroptosis, and arachidonic acid metabolism. After integrating the transcriptome and metabolomics data, it was found that 44 metabolic pathways were changed, and the significantly enriched pathways were ferroptosis and pyrimidine metabolism. CONCLUSION: Different culture methods affect the gene expression and metabolite generation of OS Saos-2 cells. Moreover, the cell and tissue culture method in vitro cannot completely simulate TME in vivo, and the ferroptosis and pyrimidine metabolism pathways mediate the functional changes of OS Saos-2 cells in different microenvironments.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Transcriptoma , Técnicas de Cultura , Osteossarcoma/genética , Neoplasias Ósseas/genética , Pirimidinas , Microambiente Tumoral
19.
Neurol India ; 70(5): 1824-1829, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352573

RESUMO

Background: Although the asterion has long been used as a skeletal surface marker of the transverse-sigmoid sinuses junction (TSSJ) point in the retrosigmoid approach, abundant evidence shows that the relationship between asterion and TSSJ point varies greatly. In recent years, new technologies have been developed, such as neuronavigation and three-dimensional volume rendering imaging, that can guide in exposing the TSSJ point individually. However, they are not only expensive but also difficult to apply in emergency surgery. Objective: To introduce a quick, practical, and low-cost new method for locating the TSSJ point precisely. Methods: In this retrospective before-after study, the test group located the TSSJ point with our new method during a 6-month period, while the control group used asterion as a surface landmark to estimate the TSSJ during the preceding 6 months. The primary outcome is the immediate exposure rate of the TSSJ point by the initial burr hole. Results: There were 60 patients in both control and test groups as no significant difference in the general clinical characteristics of both groups were observed. The new three-step method significantly increased the TSSJ exposure rate by initial burr hole compared with the control group (96.67% vs. 53.33%, P = 0.0002). Moreover, the total bone loss and craniotomy duration were significantly reduced by the new method. Incidence of sinus injury (10% vs. 6.6%), post-operation infection (3.33% vs. 3.33%), and CSF leakage (3.33% vs. 0%) were similar. Conclusions: The novel three-step approach accurately locates TSSJ points in retrosigmoid craniotomy, reduces bone defects, saves time, and does not increase the risk of sinus injury, infection, and CSF leakage.


Assuntos
Cavidades Cranianas , Craniotomia , Humanos , Estudos Retrospectivos , Estudos Controlados Antes e Depois , Cavidades Cranianas/diagnóstico por imagem , Cavidades Cranianas/cirurgia , Craniotomia/métodos , Imageamento por Ressonância Magnética
20.
ACS Appl Mater Interfaces ; 14(41): 46548-46561, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36205626

RESUMO

Improving transition metal-nitrogen-carbon (M-N-C) as a noble-metal-free catalyst for the oxygen reduction reaction (ORR) is critical to achieve low-cost electrochemical energy conversion. Herein, an in situ S doping strategy of enhancing Fe-N-C activity for ORR was developed by newly designed Fe(II) ion coordinated S-containing bis(imino)-pyridine-based polymers as precursors, which were synthesized through copolymerizing three monomers of 2, 6-diacetylpyridine (DAP), triamterene (TIT), and 2,5-dithiobiurea (DTB) as both N and S sources. All samples derived from various molar ratios of the three monomers possess a self-supporting structure of nanosheets. Additionally, incorporating DTB into the copolymer can not only strongly affect the derived coordinative species of N dopants to Fe atom but also effectively induce the synergistic effect between S dopants and FeNx moieties, resulting a significant improvement for ORR. The S-doped Fe-N-C nansheets with Fe coordinated by 4 pyrrolic N dopants exhibit the highest ORR activity and stability in alkaline media with a higher power output of Zn-air battery than that of the same loading of Pt/C. Theoretical calculation identifies that the thiophenic S dopant adjacent to Fe-pyrrolic N moiety can decrease the d band center of Fe atom, greatly weakening the energy profiles of oxygenated intermediates and thus enhancing ORR. In addition, because of the designability of transition metal coordinated S-containing bis(imino)-pyridine based polymers in the work, therefore, it is believable that this strategy would open a wide space to explore the structural relationship between precursors and MNx active sites with S dopants for the purpose of achieving highly efficient and robust M-N-C catalysts for energy-related electrocatalysis.

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