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Objective: To investigate the current state of nurses' intentions to report harmful incidents in the hematology department, and the influencing factors, to provide a relevant basis for ensuring healthcare quality and patient safety. Methods: By using a stratified sampling technique, 80 nurses from the hematology department of our hospital between June 2020 and June 2022 were randomly chosen as the research objects. The Chinese version of intention to report adverse event questionnaire (15 items with a scale of 0 to 1), adverse event report cognitive questionnaire (8 items with a scale of 0 to 1), and adverse event reporting attitude questionnaire (25 projects with a scale of 0 to 4) were used to collect data. Multiple linear regression model was used to explore the influencing variables based on the single-factor indicators with statistical significance. Results: When adverse events caused serious casualties or even death, the majority cases (96.25%) were reported to the superior supervisor; when the adverse events did not cause relevant injury, and was in potential vulnerability, the proportion of discussing with colleagues was the most (90.00% and 88.75%, respectively). For cognition on adverse events, "whether they understand the medical safety event reporting system" accounted for the most proportion (98.75%). The nurses had the highest scores for reporting standard [(25.58 ± 6.19) points] and lowest score for reporting purpose [(8.62 ± 1.51) points]. Age, educational background, years of employment, and professional titles were influencing factors of nurses' inclination to report unfavorable events (P < .05). Conclusion: The cognition and reporting attitude of nurses in the hematology department on adverse events need further improvement. The intention of the nurses to report adverse events is influenced by age, educational background, years of experience, and professional titles. Patient safety education especially with simulation-based training should be implemented, to decrease frequency of adverse incidents.
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Background: Chronic beryllium disease is characterized by granulomas and pulmonary fibrosis. Recent studies have shown that microRNAs (miRNAs) and circular RNAs (circRNAs) play critical roles in the pathogenesis and development of many diseases. However, the role of miRNAs and circRNAs in pulmonary fibrosis induced by beryllium sulfate (BeSO4) has not been elucidated. Methods: Previous studies demonstrated hsa-miR-663b was down-regulated in the 150 µmol/L BeSO4-treated 16HBE cells, while hsa_circ_ 0004214 was up-regulated. Here we found epithelial-mesenchymal transition (EMT) involved in pulmonary fibrosis induced by BeSO4 (4, 8, and 12 mg/kg·BW) in SD rats. Results: Elevated expression of hsa-miR-663b blocked the EMT progression of 16HBE cells induced by 150 µmol/L BeSO4. Notably, the overexpression of hsa-miR-663b decreased the expression of leukemia inhibitory factor (LIF), which was predicted as a target gene of hsa-miR-663b by bioinformatics tools. Furthermore, elevated miR-663b inhibited the activation of the downstream Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway induced by BeSO4 in 16HBE cells. Previous study suggested that hsa_circ_0004214 had binding sites for hsa-miR-663b. The results indicated hsa_circ_0004214 alleviated the BeSO4-induced EMT via JAK-STAT pathway in 16HBE cells. Conclusions: Collectively, the overexpression of hsa-miR-663b and knockdown of hsa_circ_0004214 attenuated the EMT induced by BeSO4 through the inhibition of JAK-STAT signaling pathway. The aberrant expressed hsa-miR-663b and hsa_circ_0004214 stimulated by BeSO4 may exert an important function in the toxic mechanism of beryllium exposure to 16HBE cells, providing the potential therapeutic targets in chronic beryllium disease.
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Optic neuropathies, such as glaucoma, are due to progressive retinal ganglion cells (RGCs) degeneration, result in irreversible vision loss. The promising RGCs replacement therapy for restoring vision are impeded by insufficient RGC-like cells sources. The present work was enriched one new type RGC-like cells using two surface markers CD184 and CD171 from human induced pluripotent stem cells (hiPSCs) by FACS sorting firstly. These new kind cells have well proliferation ability and possessed passage tolerance in vitro 2D or 3D spheroids culture, which kept expressing Pax6, Brn3b and ßIII-Tubulin and so on. The transplanted CD184+CD171+ RGC-like cells could survive and integrate into the normal and optic nerve crush (ONC) mice retina, especially they were more inclined to across the optic nerve head and extend to the damaged optic nerve. These data support the feasible application for cell replacement therapy in RGC degenerative diseases, as well as help to develop new commercial cells sorting reagents and establish good manufacturing practice (GMP) grade RGC-like donor cells for further clinical application.
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Células Madre Pluripotentes Inducidas , Traumatismos del Nervio Óptico , Ratones , Animales , Humanos , Retina , Células Ganglionares de la Retina , Nervio Óptico , Organoides , Modelos Animales de Enfermedad , Compresión NerviosaRESUMEN
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of ALL characterized by its high heterogeneity and unfavorable clinical features. Despite improved insights in genetic and epigenetic landscapes of T-ALL, the molecular mechanisms that drive malignant T-cell development remain unclear. BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription repressor recognized as a tumor suppressor in B-cell malignancies, but little is known about its function and regulatory network in T-ALL. Here we found extremely low levels of BACH2 in T-ALL clinical samples and cell lines compared to normal T cells. Overexpression of BACH2 in T-ALL cells not only induced cell growth retardation but also inhibited cancer progression and infiltration in xenografts. Further RNA sequencing (RNA-seq) analysis revealed significant alterations in regulation of defense and immune responses in T-ALL cells upon BACH2 overexpression. Strikingly, CD28 and CD40LG, two essential stimulatory molecules on T cells, were for the first time identified as novel downstream targets repressed by BACH2 in T-ALL cells. Interestingly, both CD28 and CD40LG were indispensable for T-ALL survival, since largely or completely silencing CD28 and CD40LG led to rapid cell death, whereas partial knockdown of them resulted in cell-cycle arrest and enhanced apoptosis. More importantly, BACH2-mediated CD28 and CD40LG signals contributed to cell migration and dissemination of T-ALL cells to the bone marrow, thus adding a new layer to the BACH2-mediated tumor immunoregulation in T-cell malignancies.
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Antígenos CD28 , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Linfocitos/metabolismo , Linfocitos T/metabolismoRESUMEN
Background and objectives: Endovascular thrombectomy (EVT) improves long-term outcomes and decreases mortality in ischemic stroke patients. However, a significant proportion of patients do not benefit from EVT recanalization, a phenomenon known as futile recanalization or reperfusion without functional independence (RFI). In this study, we aim to identify the major stroke risk factors and patient characteristics associated with RFI. Methods: This is a retrospective cohort study of 297 consecutive patients with ischemic stroke who received EVT at three academic stroke centers in China from March 2019 to March 2022. Patient age, sex, modified Rankin Scale (mRS), National Institute of Health Stroke Scale (NIHSS), Alberta stroke program early CT score (ASPECTS), time to treatment, risk factors and comorbidities associated with cerebrovascular diseases were collected, and potential associations with futile recanalization were assessed. RFI was successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI) ≥ 2b without functional independence at 90 days (mRS ≥ 3). Results: Of the 297 initial patients assessed, 231 were included in the final analyses after the application of the inclusion and exclusion criteria. Patients were divided by those who had RFI (n = 124) versus no RFI (n = 107). Older age (OR 1.041, 95% CI 1.004 to 1.073; p = 0.010), chronic kidney disease (OR 4.399, 0.904-21.412; p = 0.067), and higher 24-h NIHSS (OR 1.284, 1.201-1.373; p < 0.001) were independent predictors of RFI. Conversely, an mTICI score of 3 was associated with a reduced likelihood of RFI (OR 0.402, 0.178-0.909; p = 0.029). Conclusion: In conclusion, increased age, higher 24-h NIHSS and lack of an mTICI score of 3 were independently associated with RFI and have potential prognostic values in predicting patients that are less likely to respond to EVT recanalization therapy.
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ARID1A is among the most commonly mutated tumor suppressor genes in hepatocellular carcinoma (HCC). In this study, we conduct a CRISPR-Cas9 synthetic lethality screen using ARID1A-deficient HCC cells to identify approaches to treat HCC patients harboring ARID1A deficiency. This strategy reveals that the survival of these ARID1A-deficient HCC cells is highly dependent on genes related to the tricarboxylic acid (TCA) cycle. Mechanistically, ARID1A loss represses expression of key glycolysis-related gene PKM, shifting cellular glucose metabolism from aerobic glycolysis to dependence on the TCA cycle and oxidative phosphorylation. Cuproptosis is a recently defined form of copper-induced cell death reported to directly target the TCA cycle. Here, we find that ARID1A-deficient HCC cells and xenograft tumors are highly sensitive to copper treatment. Together, these results offer evidence of the synthetic lethality between ARID1A deficiency and mitochondrial respiration impairment, suggesting that copper treatment constitutes a promising therapeutic strategy for selectively targeting ARID1A-deficient HCC.
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Apoptosis , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Cobre , Proteínas de Unión al ADN/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Mutaciones Letales Sintéticas/genética , Factores de Transcripción/genéticaRESUMEN
RNA-binding protein with multiple splicing (RBPMS) plays a crucial role in cardiac mesoderm specification and cardiovascular development, as well as being a typical marker for whole retinal ganglion cells (RGCs). However, there is a lack of animal models to spatiotemporally trace the location and function of RBPMS-expressing cells in vivo. In this study, we develop a tamoxifen-inducible RBPMS-tdTomato reporter mouse line to track RBPMS-expressing cells during embryogenesis and adulthood. This mouse line allows us to identify and locate RBPMS-tdTomato-positive cells among various tissues, especially in RGCs and smooth muscle cells, which assist to simulate related retinal degenerative diseases, model and examine choroidal neovascularization non-invasively in vivo. Our results show that the RBPMSCreERT2-tdTomato mouse line is a valuable tool for lineage tracing, disease modeling, drug screening, as well as isolating specific target cells.
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BTB and CNC homology 1 (BACH1) is a transcription repressor that regulates multiple physiological processes, including intracellular heme homeostasis and immune responses. Increasing lines of evidence indicate that BACH1 reshapes metastasis and metabolism of human solid tumors. However, its potential roles in mantle cell lymphoma (MCL) remain largely unknown. Here, we found that silencing BACH1 in MCL cells induced markedly cell-cycle arrest and cell apoptosis, whereas overexpression of BACH1 exhibited the opposite patterns. Increased BACH1 levels not only promoted tumor growth and dispersal in xenografts, but also conferred a long-term poor prognosis in patients with MCL. Interestingly, RNA sequencing analysis revealed noncanonical function of BACH1 in regulation of type I interferon (IFNI) response, DNA replication and repair, and cell cycle. Mechanistically, zinc finger and BTB domain containing 20 (ZBTB20) and HMG-box transcription factor 1 (HBP1) were for the first time identified as two novel downstream targets repressed by BACH1 in MCL cells. Further double-knockdown functional assays confirmed that loss of BACH1 induced ZBTB20-mediated IFNα production and HBP1-mediated cell-cycle arrest, indicating that BACH1-centered regulatory network may be a novel targetable vulnerability in MCL cells. IMPLICATIONS: BACH1 serves as a pleotropic regulator of tumor-intrinsic innate immune response and cell-cycle progression, disruption of which may offer a promising therapeutic strategy for MCL treatment.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Linfoma de Células del Manto , Humanos , Adulto , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Linfoma de Células del Manto/genética , Puntos de Control del Ciclo Celular/genética , Ciclo Celular , Inmunidad Innata/genética , Proteínas del Grupo de Alta Movilidad , Proteínas RepresorasRESUMEN
Spinal cord injury (SCI) is a prevalent central nervous system disease with a high disability rate, leading to the loss of motor and sensory nerve function. Due to the complex pathophysiology of SCI, more effective clinical treatment strategies are needed. Research has indicated the considerable potential of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC-EVs) as a cell-free therapy in SCI repair and regeneration due to their ability to regulate immune cell activity and stimulate damaged neuron regeneration. Moreover, applying MSCs and engineered EVs can fully exploit the potential of MSC-EVs in spinal cord repair. Here, we outline the pathological process of SCI and its current clinical treatment status, summarize the latest MSC-EVs research and its pretreatment and engineering strategies in SCI treatment, and explore MSC-EVs application prospects.
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Objective: This case-control study was to explore the effect of Bushen Zhuanggu tablet combined with routine regimen on bone mineral density (BMD) improvement, functional recovery, and fracture prevention in postmenopausal osteoporosis (PMOP) patients. Methods: 180 postmenopausal osteoporosis patients were randomly selected from communities A, B, and C cohorts as research subjects from January to May 2021. The study subjects were divided into three groups. The groups were in a 1 : 1 ratio according to the principles of nonrandomised, concurrent controlled trials, and methods. There were 60 participants in each group (group A, group B, and group C). Group A was treated with Bushen Zhuanggu tablet for antiosteoporosis + basic treatment (calcium supplement and vitamin D). Group C was given Bushen Zhuanggu tablet for antiosteoporosis intervention. Group B was given basic treatment (calcium supplement and vitamin D supplementation) as a control group. The follow-up time was 6 months after treatment. Finally, we compare the differences in calcium and phosphorus metabolism indexes, BMD, bone metabolism indexes, upper and lower limb muscle strength, and quality of life scores. Results: Group A, B, and C's effective rate was 98.33%, 80.00%, and 93.33%, respectively. The group A's effective rate was significantly higher than that in group B and C, and the difference was statistically significant (P < 0.05). After 6 months intervention, the levels of serum Ca2+, serum phosphorus (P), serum creatinine (Cr), and parathyroid hormone (PTH) in 3 groups decreased. Ca, P, Scr, and PTH levels in group A were the lowest among study groups, and the difference was statistically significant (P < 0.05). The increase in the BMD of lumbar spine, the left femoral neck, and Ward's triangle area of the three groups were observed with the highest data in group A. After 6 months of treatment, the levels of serum N-terminal propeptide of type I procollagen, PINP, and serum osteocalcin (OC) increased, while the levels of ß-cross-linked C-terminal telopeptide of type I collagen (ß-CTX) and alkaline phosphatase (ALP) decreased in the three groups. The improvement of all bone metabolic indexes in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). The enhanced upper limb muscle strength and the shorter standing-walking timing test (TUGT) time were observed after 6 months of treatment. The improvement effect of upper and lower limb muscle strength in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). There were significant differences in physiological function, life function, general health status, physical pain, mental state, emotional function, vitality, and social function among the three groups after 6 months treatment, and the difference was statistically significant (P < 0.05). The score of quality of life in group A was higher than that in B and C groups, and the difference was statistically significant (P < 0.05). Conclusion: Bushen Zhuanggu tablet combined with conventional therapy is effective in the postmenopausal osteoporosis treatment, which effectively increase the BMD, regulate calcium and phosphorus metabolism, promote the recovery of limb function, prevent the recurrence of fracture, and improve the patients' quality of life. This treatment scheme is worth popularizing.
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Fracturas Óseas , Osteoporosis Posmenopáusica , Femenino , Humanos , Densidad Ósea , Calcio , Estudios de Casos y Controles , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/prevención & control , Osteoporosis Posmenopáusica/metabolismo , Fósforo/farmacología , Calidad de Vida , Vitamina D/uso terapéuticoRESUMEN
BACKGROUND: Impairment of the hematopoietic system is one of the primary adverse health effects from exposure to benzene. We previously have shown that exposure to benzene at low levels (<1 ppm) affects the blood forming system and that these effects were proportionally stronger at lower versus higher levels of benzene exposure. This observation is potentially explained by saturation of enzymatic systems. METHODS: Here we extend these analyses by detailed modeling of the exposure response association of benzene and its major metabolites (i.e. catechol, muconic acid, phenol, and hydroquinone) on peripheral white blood cell (WBC) counts and its major cell-subtypes (i.e. granulocytes, lymphocytes, and monocytes) using two previously published cross-sectional studies among occupationally exposed Chinese workers. RESULTS: Supra-linear exposure response associations were observed between air benzene concentrations (range â¼ 0.1 - 100 ppm) and WBC counts and its cell-subtypes, with a larger than proportional decrease in cell counts at lower than at higher levels of benzene exposure. The hematotoxicity associations were largely similar in shape when the analyses were repeated with benzene urinary metabolites suggesting that enzymatic saturation is not a full explanation of the observed non-linearity with WBC endpoints. DISCUSSION: We hypothesize that the flattening of the exposure response curve especially at higher benzene exposure levels may reflect a response by the bone marrow to maintain hematopoietic homeostasis. Toxicity to the bone marrow and an induced hyper-proliferative response could both contribute to risk of subsequently developing a hematopoietic malignancy. Additional work is needed to explore this hypothesis.
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Benceno , Exposición Profesional , Humanos , Benceno/toxicidad , Benceno/análisis , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Estudios Transversales , Pueblos del Este de Asia , Fenoles/orinaRESUMEN
Beryllium sulfate (BeSO4 ) can result to lung injuries, such as leading to lipid peroxidation and autophagy, and the treatment of beryllium disease has not been well improved. Ferroptosis is a regulated cell death process driven by iron-dependent and lipid peroxidation, while ferritinophagy is a process mediated by nuclear receptor coactivator 4 (NCOA4), combined with ferritin heavy chain 1 (FTH1) degradation and release Fe2+ , which regulated intracellular iron metabolism and ferroptosis. Hydrogen sulfide (H2 S) has the effects of antioxidant, antiautophagy, and antiferroptosis. This study aimed to investigate the effect of H2 S on BeSO4 -induced ferroptosis and ferritinophagy in 16HBE cells and the underlying mechanism. In this study, BeSO4 -induced 16HBE cell injury model was established based on cellular level and pretreated with deferoxamine (DFO, a ferroptosis inhibitor), sodium hydrosulfide (NaHS, a H2 S donor), or NCOA4 siRNA and, subsequently, performed to detect the levels of lipid peroxidation and Fe2+ and the biomarkers of ferroptosis and ferritinophagy. More importantly, our research found that DFO, NaHS, or NCOA4 siRNA alleviated BeSO4 -induced ferroptosis and ferritinophagy by decreasing the accumulation of Fe2+ and lipid peroxides. Furthermore, the relationship between ferroptosis, ferritinophagy, H2 S, and beryllium disease is not well defined; therefore, our research is innovative. Overall, our results provided a new theoretical basis for the prevention and treatment of beryllium disease and suggested that the application of H2 S, blocking ferroptosis, and ferritinophagy may be a potential therapeutic direction for the prevention and treatment of beryllium disease.
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Beriliosis , Ferroptosis , Sulfuro de Hidrógeno , Humanos , Sulfuro de Hidrógeno/farmacología , Autofagia , Hierro/toxicidad , ARN Interferente Pequeño , Factores de TranscripciónRESUMEN
Cancer-associated factors have been largely identified in the understanding of tumorigenesis and progression. However, aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) have so far been neglected in cancer research due to their canonical activities in protein translation and synthesis. FARSA, the alpha subunit of the phenylalanyl-tRNA synthetase is elevated across many cancer types, but its function in mantle cell lymphoma (MCL) remains undetermined. Herein, we found the lowest levels of FARSA in patients with MCL compared with other subtypes of lymphomas, and the same lower levels of FARSA were observed in chemoresistant MCL cell lines. Unexpectedly, despite the essential catalytic roles of FARSA, knockdown of FARSA in MCL cells did not lead to cell death but resulted in accelerated cell proliferation and cell cycle, whereas overexpression of FARSA induced remarkable cell-cycle arrest and overwhelming apoptosis. Further RNA sequencing (RNA-seq) analysis and validation experiments confirmed a strong connection between FARSA and cell cycle in MCL cells. Importantly, FARSA leads to the alteration of cell cycle and survival via both PI3K-AKT and FOXO1-RAG1 axes, highlighting a FARSA-mediated regulatory network in MCL cells. Our findings, for the first time, reveal the noncanonical roles of FARSA in MCL cells, and provide novel insights into understanding the pathogenesis and progression of B-cell malignancies.
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Linfoma de Células del Manto , Adulto , Humanos , Apoptosis/genética , Ciclo Celular/genética , Ciclo Celular/fisiología , Línea Celular Tumoral , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Proteínas de Homeodominio , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/metabolismo , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/patología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Wound infection is a major problem faced during wound healing. Therefore, it is necessary to develop wound dressings with excellent antimicrobial properties. Here, a smart response system of PVA-TPE/HA-AMP/SF/ALG wound dressing was prepared by a combination of chemical cross-linking and freeze-drying methods. We grafted AMP onto HA to endow the wound dressing with bacterial resistance and slow release of AMP. At the same time, the system detects bacterial activity in real time for precise antimicrobial activity (through the use of PVA-TPE) and modulates inflammation to reduce bacterial infection (through the use of AMP). In addition, the PVA-TPE/HA-AMP/SF/ALG wound dressing has a good three-dimensional mesh structure, which promotes cell proliferation, enhances collagen deposition and angiogenesis, and thus effectively promotes rapid healing of infected wounds. Moreover, it can induce the expression of inflammatory factors such as VEGF, TNF-α, IFN-γ, IL-4 and TGF-ß1 in infected wounds through the Wnt/CAMK/p-PKC signaling pathway, inhibit inflammatory responses, promote wound healing and reduce scar formation. Therefore, the PVA-TPE/HA-AMP/SF/ALG wound dressing smart response system shows great promise in infected wound healing.
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Sweetpotato (Ipomoea batatas L.) with different depths of yellow color contains different compositions of carotenoids, which are beneficial for human health. In this study, we performed an integrated analysis of metabolomic and transcriptomic to identify key genes playing a major role in carotenoid coloration in sweetpotato tuberous roots. Herein, 14 carotenoids were identified in five sweetpotatoes. Orange-red and orange cultivars were dominated by ß-carotene (385.33 µg/g and 85.07 µg/g), yellow cultivar had a high ß-cryptoxanthin (11.23 µg/g), light-yellow cultivar was rich in zeaxanthin (5.12 µg/g), whereas lutein (3.34 µg/g) was the main carotenoid in white cultivar. Furthermore, 27 differentially expressed genes involved in carotenoid metabolism were identified based on comparative transcriptome. Weighted gene co-expression network analysis identified 15 transcription factors highly associated with carotenoid content in sweetpotatoes. These results provide valuable information for revealing the regulatory mechanism of carotenoid metabolism in different-colored sweetpotato tuberous roots.
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Replenishing the retina with retinal pigment epithelial (RPE) cells derived from pluripotent stem cells (PSCs) has great promise for treating retinal degenerative diseases, but it is limited by poor cell survival and integration in vivo. Herein, porcine acellular sclera and uvea extracellular matrix (ECM) and their counterpart hydrogels are developed, and their effects on the biological behavior of human induced pluripotent stem cell (hiPSC)-derived RPE cells (hiPSC-RPE) and embryoid body (hiPSC-EB) differentiation are investigated. Both acellular ECM hydrogels have excellent biocompatibility and suitable biodegradability without evoking an obvious immune response. Most importantly, the decellularized uvea hydrogel-delivered cells' injection remarkably promotes the hiPSC-RPE cells' survival and integration in the subretinal space, rescues the photoreceptor cells' death and retinal gliosis, and restores vision in rats with retinal degeneration for a long duration. In addition, medium supplementation with decellularized uvea peptides promotes hiPSC-EBs onset morphogenesis and neural/retinal differentiation, forming layered retinal organoids. This study demonstrates that ECM hydrogel-delivered hiPSC-RPE cells' injection may be a useful approach for treating retinal degeneration disease, combined with an optimized retinal seeding cells' induction program, which has potential for clinical application.
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Células Madre Pluripotentes Inducidas , Degeneración Retiniana , Humanos , Animales , Ratas , Porcinos , Degeneración Retiniana/tratamiento farmacológico , Hidrogeles/farmacologíaRESUMEN
Background: Beryllium and its compounds are carcinogenicity, but the mechanisms through which this occurs have yet to be clarified. Accumulating evidence exists that long noncoding RNAs (lncRNAs) play an important role in occurrence and development of cancer. Aims and Methods: To explore the carcinogenic mechanism of beryllium, human bronchial epithelial cells (16HBE) were treated with 50 µM beryllium sulfate (BeSO4) for 45 passages (~23 weeks). The expression levels of lncRNA SNHG7, SNHG11, SNHG15, MIR22HG, GMPS, and SIK1 were detected at passage 0 (P0), 15 (P15), 25 (P25), 35 (P35), and 45 (P45). Results: The results indicated that enhanced cell proliferation, extensive clones in soft agar, protein expressions of up-regulated matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), proliferating cell nuclear antigen (PCNA), cyclin D1, and down-regulated p53 were all observed at the 45th passage in 16HBE cells. Thus, BeSO4-transformed 16HBE cells (T-16HBE) were established. Meanwhile, the study found that the expression of lncRNA SNHG11 was elevated during malignant transformation. Knockdown of SNHG11 in T-16HBE cells blocked cell proliferation, invasion, and migration, and decreased the protein levels of MMP9, MMP2, PCNA, cyclin D1, but increased p53. Conclusions: The studies revealed that SNHG11 acts as an oncogene in the malignant transformation of 16HBE cells induced by BeSO4, which signifies progress in the study of the carcinogenic mechanism of beryllium.
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Metallic Bi, as an alloying-type anode material, has demonstrated tremendous potential for practical application of potassium-ion batteries. However, the giant volume expansion, severe structure pulverization, and sluggish dynamics of Bi-based materials result in unsatisfied rate performance and unstable cycling stability. Here, 2D bismuth@N-doped carbon sheets with BiOC bond and internal void space (2D Bi@NOC) are successfully fabricated via a self-template strategy to address these issues, which own ultrafast electrochemical kinetics and impressive long-term cycling stability for delivering an admirable capacity of 341.7 mAh g-1 after 1000 cycles at 10 A g-1 and impressive rate capability of 220.6 mAh g-1 at 50 A g-1 . Particularly, the in situ transmission electron microscopy observations visualize the real-time alloying/dealloying process and reveal that plastic carbon shell and void space can availably relieve dramatic volume stress and powerfully maintain structural integrity. Density functional theory calculation and ultraviolet photoelectron spectroscopy test certify that the robust BiOC bond is thermodynamically and kinetically beneficial for adsorption/diffusion of K+ . This work will light on designing advanced high-performance energy materials and provide important evidence for understanding the energy storage mechanism of alloy-based materials.
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Background: To date, only 25 cases of cerebral infarction following a bee or wasp sting have been reported. Due to its rarity, undefined pathogenesis, and unique clinical features, we report a case of a 62-year-old man with progressive cerebral infarction following bee stings, possibly related to vasospasm. Furthermore, we review relevant literature on stroke following bee or wasp stings. Case presentation: A 62-year-old retired male presented with progressive ischemic stroke after bee stings to the ear and face. Initial magnetic resonance imaging of the brain showed small punctate infarcts in the left medulla oblongata. Head and neck computed tomography angiography showed significant stenosis in the basilar artery and occlusion in the left V4 vertebral artery. The patient received intravenous alteplase (0.9 mg/kg) without symptomatic improvement. Digital subtraction angiography later demonstrated additional near occlusion in the left posterior cerebral artery (PCA). Thrombectomy was considered initially but was aborted due to hemodynamic instability. Repeated CT brain after 24 h showed acute infarcts in the left parieto-occipital region and left thalamus. The near occluded PCA was found to be patent again on magnetic resonance angiography (MRA) 25 days later. This reversibility suggests that vasospasm may have been the underlying mechanism. Unfortunately, the patient had persistent significant neurological deficits after rehabilitation one year later. Conclusion: Cerebral infarction following bee stings is rare. There are several proposed pathophysiological mechanisms. While the natural course of this phenomenon is not well characterized, early diagnosis and treatment are essential. Furthermore, it is important to establish standardized care procedures for this unique entity.
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The N6-methyladenosine (m6A) refers to the methylation of the N6 position of adenosine of RNA adenine. The modification of m6A is one of the most abundant epigenetic modifications in eukaryotic mRNA and non-coding RNA and is controlled by methyltransferases and demethylases. The biological mechanism and significance of m6A have been discovered with the development of m6A sequencing. Various m6A complex components regulate the function of m6A on mRNA. Methyltransferase-like 3 (METTL3) is one of the earliest identified m6A methyltransferases which regulate the functions of m6A. A large number of studies have shown that METTL3 establishes a cross-talk with tumor cells and development of various human diseases. In this review, we will briefly elaborate on the role of METTL3 in biological function, epithelial-mesenchymal transition (EMT), inflammatory response and sensitivity to the resistance of chemo radiotherapies. The underlying molecular mechanism demonstrated by METTL3 may provide a possible target for treating and diagnosing human diseases.