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1.
Artigo em Chinês | MEDLINE | ID: mdl-39118515

RESUMO

Objective:To explore the effect of surgical treatment of the pulsatile tinnitus associated with sigmoid sinus on the dominant side of reflux. Methods:The clinical data of 43 patients with reflux dominant side pulsating tinnitus admitted by the same doctor from 2017 to 2023 were retrospectively studied to observe the curative effect of surgical treatment. Operation method: The sound insulation barrier was established by repair technique of bone wall defect of sigmoid sinus with "capping method", without changing the blood flow and blood vessel wall of sigmoid sinus. Results:No surgical complications occurred in all patients. During the follow-up period of 3 months to 6.9 years, 14 patients(32.6%) were cured, 18 patients(41.9%) were significantly effective, 4 patients(9.3%) were effective, and 7 patients(16.3%) were ineffective. The difference of tinnitus grade before and after surgery was statistically significant. Conclusion:In this group of cases, the sound insulation barrier was established by "capping method" technique of repairing bone wall defect of sigmoid sinus, which effectively avoided the disturbance of hemorheology status and vascular wall, thus avoiding the risk of venous wall stenosis and thrombosis on the dominant reflux side. The surgical method was easy to master, and the curative effect was significant, which was worthy of clinical promotion.


Assuntos
Cavidades Cranianas , Zumbido , Humanos , Zumbido/etiologia , Zumbido/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Cavidades Cranianas/cirurgia , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade
2.
Front Neurol ; 15: 1413904, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39099781

RESUMO

Introduction: Brain edema is a life-threatening complication that occurs after glioma surgery. There are no noninvasive and specific treatment methods for brain edema. Hydrogen is an anti-inflammatory and antioxidant gas that has demonstrated therapeutic and preventative effects on several diseases, particularly in the nervous system. This study aimed to determine the therapeutic effects of hydrogen administration on brain edema following glioma surgery and elucidate its mechanism. Methods: A single-center, randomized controlled clinical trial of hydrogen inhalation was conducted (China Clinical Trial Registry [ChiCTR-2300074362]). Participants in hydrogen (H) group that inhaled hydrogen experienced quicker alleviation of postoperative brain edema compared with participants in control (C) group that inhaled oxygen. Results: The volume of brain edema before discharge was significantly lower in the H group (p < 0.05). Additionally, the regression rate of brain edema was higher in the H group than in the C group, which was statistically significant (p < 0.05). Furthermore, 3 days after surgery, the H group had longer total sleep duration, improved sleep efficiency, shorter sleep latency, and lower numerical rating scale (NRS) scores (p < 0.05). Discussion: In conclusion, hydrogen/oxygen inhalation effectively reduced postoperative brain edema in glioma patients. Further research is necessary to understand the underlying mechanisms of hydrogen's therapeutic effects. Hydrogen is expected to become a new target for future adjuvant therapy for brain edema.

3.
Front Cell Dev Biol ; 12: 1375354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100091

RESUMO

Background: In some patients, persistent gastrointestinal symptoms like abdominal pain, nausea, and diarrhea occur as part of long COVID-19 syndrome following acute respiratory symptoms caused by SARS-CoV-2. However, the characteristics of immune cells in the gastrointestinal tract of COVID-19 patients and their association with these symptoms remain unclear. Methodology: Data were collected from 95 COVID-19 patients. Among this cohort, 11 patients who exhibited gastrointestinal symptoms and underwent gastroscopy were selected. Using imaging mass cytometry, the gastrointestinal tissues of these patients were thoroughly analyzed to identify immune cell subgroups and investigate their spatial distribution. Results: Significant acute inflammatory responses were found in the gastrointestinal tissues, particularly in the duodenum, of COVID-19 patients. These alterations included an increase in the levels of CD68+ macrophages and CD3+CD4+ T-cells, which was more pronounced in tissues with nucleocapsid protein (NP). The amount of CD68+ macrophages positively correlates with the number of CD3+CD4+ T-cells (R = 0.783, p < 0.001), additionally, spatial neighborhood analysis uncovered decreased interactions between CD68+ macrophages and multiple immune cells were noted in NP-positive tissues. Furthermore, weighted gene coexpression network analysis was employed to extract gene signatures related to clinical features and immune responses from the RNA-seq data derived from gastrointestinal tissues from COVID-19 patients, and we validated that the MEgreen module shown positive correlation with clinical parameter (i.e., Total bilirubin, ALT, AST) and macrophages (R = 0.84, p = 0.001), but negatively correlated with CD4+ T cells (R = -0.62, p = 0.004). By contrast, the MEblue module was inversely associated with macrophages and positively related with CD4+ T cells. Gene function enrichment analyses revealed that the MEgreen module is closely associated with biological processes such as immune response activation, signal transduction, and chemotaxis regulation, indicating its role in the gastrointestinal inflammatory response. Conclusion: The findings of this study highlight the role of specific immune cell groups in the gastrointestinal inflammatory response in COVID-19 patients. Gene coexpression network analysis further emphasized the importance of the gene modules in gastrointestinal immune responses, providing potential molecular targets for the treatment of COVID-19-related gastrointestinal symptoms.

4.
Front Cell Dev Biol ; 12: 1436420, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100095

RESUMO

Vacuole membrane protein 1 (VMP1) is an integral membrane protein that plays a pivotal role in cellular processes, particularly in the regulation of autophagy. Autophagy, a self-degradative mechanism, is essential for maintaining cellular homeostasis by degradation and recycling damaged organelles and proteins. VMP1 involved in the autophagic processes include the formation of autophagosomes and the subsequent fusion with lysosomes. Moreover, VMP1 modulates endoplasmic reticulum (ER) calcium levels, which is significant for various cellular functions, including protein folding and cellular signaling. Recent studies have also linked VMP1 to the cellular response against viral infections and lipid droplet (LD). Dysregulation of VMP1 has been observed in several pathological conditions, including neurodegenerative diseases such as Parkinson's disease (PD), pancreatitis, hepatitis, and tumorogenesis, underscoring its potential as a therapeutic target. This review aims to provide an overview of VMP1's multifaceted roles and its implications in disease pathology.

5.
Mar Pollut Bull ; 206: 116786, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39094283

RESUMO

The fractionation and distribution of two potentially toxic elements (Co and Ni) were investigated in surface sediments to explore the pollution in Xiamen Bay, a special zone experiencing rapid economic growth and enormous environmental pressure. Relatively high concentrations were observed in nearshore areas with frequent human activities. The dominant fractions for Co and Ni were found to be residual, followed by exchangeable phase. Spatial differences in mobility and bioavailability inferred from chemical fractionations were more pronounced for Ni. Multiple evaluation methods including geo-accumulation index, risk assessment code, modified potential ecological risk index, etc., consistently indicated that pollution levels and ecological risks in the entire bay were generally classified as medium-low. However, non-carcinogenic risks of Co for children and carcinogenic risks of Ni for adults exceeded safety thresholds. Terrestrial weathering processes and industrial activities primarily contributed to the presence of these elements, while their distributions were mainly influenced by organic matter.

6.
J Colloid Interface Sci ; 677(Pt A): 158-166, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39089124

RESUMO

Tailoring the dynamic reconstruction of transition metal compounds into highly active oxyhydroxides through surface electron state modification is crucial for advancing water oxidation, yet remains a formidable challenge. In this study, a unique polyaniline (PANI) electron bridge was integrated into the metal-organic frameworks (MOFs)/layer double hydroxides (LDHs) heterojunction to expedite electron transfer from MOFs to LDHs, facilitating electron accumulation at the metal sites within MOF and electron-deficient LDHs. This configuration promotes the surface dynamic reconstruction of LDHs into highly active oxyhydroxides while safeguarding the MOF from corrosion in harsh environments over extended periods. The optimized electronic structure modification of both MOFs and LDHs enhances reaction kinetics. The superior MIL-88B(Fe)@PANI@NiCo LDH catalyst achieved 10 mA∙cm-2 at an overpotential of 202 mV and demonstrated stable operation for 120 h at this current density. This research introduces an innovative approach for guiding electron transfer and dynamic catalyst reconstruction by constructing a PANI electron bridge, potentially paving the way for more efficient catalytic systems.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39093637

RESUMO

Antibody-drug conjugates (ADCs), which combine the precise targeting capabilities of antibodies with the powerful cytotoxicity of small-molecule drugs, have evolved into a promising approach for tumor treatment. However, the traditional covalent coupling method requires the design of a specific linker tailored to the properties of the small-molecule drugs, which greatly limits the development of ADCs and the range of drugs that can be used. Herein, a novel type of antibody-calixarene drug conjugates (ACDCs) that function similarly to ADCs by delivering drugs to their targets using antibodies but without the requirement of covalent conjugation of the drugs with antibodies is presented. By replacement of conventional linkers with supramolecular linkers, the ACDCs can load various chemotherapeutic drugs through host-guest interactions. Furthermore, ACDCs are readily reduced upon reaching the hypoxic microenvironment, resulting in rapid release of the drugs. With this precise drug encapsulation and controlled release mechanism, ACDCs deliver drugs to tumor tissues effectively and achieve a significantly enhanced antitumor effect. Considering that the ACDCs can be easily prepared by combining antibody-calixarene conjugates derived from tumor-targeting antibodies with various small-molecule drugs, ACDCs may provide a promising platform technology to accelerate ADC development and thus improve the therapeutic efficacy of chemotherapy.

8.
Blood ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093981

RESUMO

DNA methyltransferase inhibitor decitabine plus anti-PD-1 (DP) combination therapy was effective in relapsed/refractory classic Hodgkin lymphoma (cHL). However, a subset of patients experienced primary resistance or relapse/progression after DP therapy. In this study, we evaluated the efficacy and safety of a triplet regimen consisting of the histone deacetylase inhibitor chidamide, decitabine and anti-PD-1 camrelizumab (CDP) in 52 patients with relapsed/refractory cHL who had previously received DP therapy (NCT04233294). CDP treatment was well-tolerate and resulted in an objective response rate of 94% (95% CI, 84-99%), with 50% (95% CI, 36-64%) of patients achieving complete response (CR). Notably, all patients who were recalcitrant to previous DP treatment exhibited therapeutic responses following CDP therapy, although their CR rate was lower compared to patients responsive to prior DP. Overall, the median progression-free survival following CDP therapy was 29.4 months. Through single-cell RNA sequencing of pre-treatment and on-treatment cHL tumor biopsies, we observed the heterogeneity of rare malignant Hodgkin Reed/Sternberg (HRS)-like cells. The classical CD30+ HRS-like cells interacted with the abundant immunosuppressive IL21+CD4+ T helper cells, forming a positive feedback loop that supported their survival. In contrast, the CD30- HRS-like cell population showed potential resistance to anti-PD-1 immunotherapy. CDP treatment promoted the activation of diverse tumor-reactive CD8+ T cells and suppressed the proliferation of IL21+CD4+ T cells by inhibiting STAT1/3 signaling, thereby alleviating their immunosuppressive effects. These findings provide insights into the cHL microenvironment that contributes to anti-PD-1 resistance and highlight the therapeutic effectiveness of dual epi-immunotherapy in overcoming immunotherapy resistance.

9.
Sci Total Environ ; 949: 175206, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39094659

RESUMO

This study investigated the impact of residual anaerobic granular sludge (AnGS) from anaerobic digesters treating molasses wastewater on ammonium reduction in a downstream aerobic granular sludge (AGS) reactor. Two conditions were tested: raw (high AnGS concentration) and settled (low AnGS concentration) anaerobically digested molasses wastewaters were fed into the AGS reactor. With the introduction of raw wastewater, enhanced nitrite accumulation at 30 % and improved total inorganic nitrogen (TIN) removal at 11 % were observed compared to 1 % nitrite accumulation and 8 % TIN removal with the introduction of settled wastewater. However, AnGS adversely affected other aspects of reactor performance, increasing effluent solid content and decreasing soluble chemical oxygen demand removal efficiency from 20 % in the low AnGS condition to 11 % in the high AnGS condition. Despite the observed retention of AnGS in the reactor, no significant bioaugmentation effects on the microbial community of the AGS were observed. Aerobic granular sludge was consistently observed in both conditions. The study suggests that AnGS may act as a nucleus for granule formation, helping to maintain granule stability in a disturbed environment. This study offers a systematic understanding of the impact of AnGS on subsequent nitrogen removal process using AGS, aiding in the decision making in the treatment of high solid anaerobic digestate.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39096204

RESUMO

AIMS: Deposition of extracellular matrix (ECM) in the trabecular meshwork (TM), as induced by dexamethasone (DEX), is believed to play an important role in the onset of glucocorticoid-induced glaucoma (GIG). Abnormal ECM deposition is a consequence of mitochondrial dysfunction. We aimed to clarify how mitochondrial dysfunction leads to ECM deposition within the TM and to support the development of novel therapeutic strategies. RESULTS: In primary human TM cells (pHTMCs) and a dexamethasone acetate-induced murine model of GIG, glucocorticoid administration stimulated both mitochondrial fission and ECM deposition. Excessive mitochondrial fission leads to dysfunction and the overexpression of ECM proteins in pHTMCs. Notably, when pHTMCs were treated with the Drp1 inhibitor Mdivi-1 or with Drp1 siRNA, we observed a marked reduction in DEX-induced mitochondrial damage and ECM proteins in vitro. Furthermore, in C57BL/6J mice, treatment with Mdivi-1 mitigated mitochondrial damage and blocked ECM deposition within the TM. We then employed Ro3306 to inhibit the CDK1-mediated phosphorylation of Drp1 at Ser 616, which restored mitochondrial function and diminished DEX-induced ECM protein expression in pHTMCs. INNOVATION: This study illuminates the pathogenic mechanism linking mitochondrial dysfunction to ECM deposition in GIG. Our innovative approach revealed that DEX stimulates mitochondrial fission via CDK1-mediated p-Drp1s616 overexpression, which drives ECM accumulation. It offered a novel therapeutic strategy for reducing ECM protein expression by inhibiting excessive mitochondrial fission and restoring mitochondrial function. CONCLUSION: By targeting the CDK1/Drp1-driven mitochondrial fission process, we can counteract DEX-induced ECM deposition in the TM both in vivo and in vitro.

11.
Artigo em Inglês | MEDLINE | ID: mdl-39096308

RESUMO

SiOx anode materials are among the most promising candidates for next-generation high-energy-density lithium-ion batteries (LIBs). However, their commercial application is hindered by poor conductivity, low initial Coulombic efficiency (ICE), and an unstable solid electrolyte interface. Developing cost-effective SiOx anodes with high electrochemical performance is crucial for advanced LIBs. To tackle these issues, this study utilized APTES as a silicon source and carbon nanotubes (CNTs) as additives to prepare a T-SiOx/C/CNTs composite material with N doping and in situ carbon coating using a "molecular assembly combined with controlled pyrolysis" strategy under mild conditions. The in situ carbon coating, formed by the pyrolysis of organic groups on the molecular precursor, effectively protects the inner SiOx active material. The introduced CNTs enhance electron migration and improve the rigidity of the carbon coating layer. The prelithiated T-SiOx@C/CNTs electrode achieves an ICE of 91.6%, with a specific capacity of 622 mAh g-1 after 400 cycles at 1 A g-1 and 475.8 mAh g-1 after 800 cycles. Full cell tests with commercial NCM811 cathodes further demonstrate the potential of T-SiOx@C/CNTs as a highly promising anode material. This work provides some insights into the rational design of advanced anode materials for LIBs, paving the way for their future development and application.

12.
Curr Med Sci ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096475

RESUMO

OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.

13.
Spectrochim Acta A Mol Biomol Spectrosc ; 323: 124916, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39096679

RESUMO

Quality of pet foods can be affected by many factors such as raw materials, formulations, and processing techniques. The pet food manufacturers require fast analyses to control the nutritional quality of their products. Herein, near-infrared spectroscopy (NIR) was evaluated to quantify the chemical composition of pet food, and the performances of two NIR spectrometers were investigated and compared: a benchtop instrument (1000-2500 nm) and a low-cost handheld instrument (900-1700 nm). Seventy cat food and thirty-six dog samples were characterized using reference methods for crude protein, crude fat, crude fibre, crude ash, moisture, calcium (Ca), and phosphorus (P). Principal component regression (PCR) and partial least squares regression (PLSR) were used to establish the models that involved the cat food and mixed model. The characteristic wavelengths were selected using a competitive adaptive reweighted-sampling (CARS) algorithm. The Optimal models obtained from the benchtop instrument for crude protein, crude fat, and moisture were classified as "Good" or "Very good" (Residual prediction variation (RPD) > 3), for crude fibre were classified as "Poor" (RPD>2), and for crude ash, Ca and P (RPD<2) were classified as "Very poor". The Optimal calibrations obtained from the handheld instrument for crude protein, crude fat, and moisture were classified as "Good" or "Very good" (RPD>3), for crude fibre, crude ash, Ca, and P were classified as "Very poor" (RPD<2). Generally, the the performance of benchtop and handheld instrument was close, and the cat food model outperformed the mixed model. Results from the current study revealed the potential to monitor the chemical compositions in pet food on a large scale.

14.
Am J Obstet Gynecol MFM ; : 101436, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39096968

RESUMO

BACKGROUND: Induction of labor with mechanical methods or pharmacological agents is used in about 20-30% of all pregnant women. We specialized in comparing the effectiveness and safety of dinoprostone versus transcervical Foley catheter for induction of labor in term pregnant women with an unfavorable cervix with adequate samples. OBJECTIVE: To compare the effectiveness and safety of dinoprostone versus transcervical Foley catheter for induction of labor in term pregnant women with an unfavorable cervix. STUDY DESIGN: This is a parallel, open-label randomized controlled trial in two maternal centers in Shanghai, China between October 2019 and July 2022. Women with a singleton pregnancy in cephalic presentation at term and an unfavorable cervix (Bishop score < 6) scheduled for induction of labor were eligible. 1,860 women were randomly allocated to cervical ripening with either a dinoprostone vaginal insert (10mg) or a 60cc Foley catheter for up to 24 hours. The primary outcomes were vaginal delivery rate and time to vaginal delivery. Secondary outcomes included time to delivery and maternal and neonatal morbidity. Analysis was done from an intention-to-treat perspective. The trial was registered with the China trial registry (CTR2000038435). RESULTS: The vaginal birth rates were 72.8% (677/930) vs. 69.9% (650/930) in vaginal dinoprostone and Foley catheter, respectively (aRR 1.04, 95% CI 0.98 to 1.10, risk difference: 0.03). Time to vaginal delivery was not significantly different between the two groups (sub-distribution hazard ratio 1.11, 95% CI 0.99-1.24). Vaginal dinoprostone was more likely complicated with hyperstimulation with fetal heart rate changes (5.8% vs. 2.8%, aRR 2.09, 95% CI 1.32-3.31) and placenta abruption (0.9% vs. 0.1%, aRR: 8.04, 95% CI 1.01-64.15), while Foley catheter was more likely complicated with suspected intrapartum infection (5.1% vs. 8.2 %, aRR: 0.62, 95% CI 0.44-0.88) and postpartum infection (1.4% vs. 3.7%, aRR: 0.38, 95% CI 0.20-0.72). The composite of poor neonatal outcomes was not significantly different between the two groups (4.5% vs. 3.8%, aRR 1.21, 95% CI 0.78 to 1.88), while more neonatal asphyxia occurred in the dinoprostone group (1.2% vs. 0.2%, aRR 5.39, 95% CI 1.22 to 23.92). In a subgroup analysis, vaginal dinoprostone decreased vaginal birth rate slightly in multiparous women (90.6% vs. 97.0%, aRR 0.93, 95% CI 0.88 to 0.99). CONCLUSIONS: In term pregnant women with an unfavorable cervix, induction of labor with vaginal dinoprostone or Foley catheter has similar effectiveness. Foley catheter leads to better safety for neonates, while it may result in a higher risk of maternal infection. Furthermore, Foley catheter should be preferred in multiparous women.

15.
Artigo em Inglês | MEDLINE | ID: mdl-39092619

RESUMO

Dental caries, the most prevalent chronic disease across all age groups, has a high prevalence, particularly among children. However, there is no specific and effective treatment for the prevention of caries in primary teeth (Pr.T.), which stems from a lack of knowledge regarding the basic nature of the tooth surface. Herein, we observed that the adhesion energies of the caries-related bacteria Streptococcus mutans and Streptococcus sanguinis to Pr.T were approximately 10 and 5.5 times higher than those to permanent teeth (Pe.T). A lower degree of mineralization and more hydrophilic characteristics of the Pr.T enamel account for this discrepancy. Accordingly, we proposed that the on-target modification of both hydroxyapatite and organic components on Pr.T by dual modification would render a sufficient hydration layer. This resulted in an approximately 11-time decrease in bacterial adhesion energy after treatment. In contrast, a single hydroxyapatite modification on Pe.T and young permanent teeth (Y.Pe.T) was sufficient to achieve a similar effect. Theoretical simulation further verified the rationality of the approach. Our findings may help understand the reason for Pr.T being caries-prone and provide references for treatment using resin restorations. This strategy offers valuable insights into daily oral hygiene and dental prophylactic treatment in children.

16.
FASEB J ; 38(15): e23848, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39092889

RESUMO

Glucocorticoid use may cause elevated intraocular pressure, leading to the development of glucocorticoid-induced glaucoma (GIG). However, the mechanism of GIG development remains incompletely understood. In this study, we subjected primary human trabecular meshwork cells (TMCs) and mice to dexamethasone treatment to mimic glucocorticoid exposure. The myofibroblast transdifferentiation of TMCs was observed in cellular and mouse models, as well as in human trabecular mesh specimens. This was demonstrated by the cytoskeletal reorganization, alterations in cell morphology, heightened transdifferentiation markers, increased extracellular matrix deposition, and cellular dysfunction. Knockdown of Rho guanine nucleotide exchange factor 26 (ARHGEF26) expression ameliorated dexamethasone-induced changes in cell morphology and upregulation of myofibroblast markers, reversed dysfunction and extracellular matrix deposition in TMCs, and prevented the development of dexamethasone-induced intraocular hypertension. And, this process may be related to the TGF-ß pathway. In conclusion, glucocorticoids induced the myofibroblast transdifferentiation in TMCs, which played a crucial role in the pathogenesis of GIG. Inhibition of ARHGEF26 expression protected TMCs by reversing myofibroblast transdifferentiation. This study demonstrated the potential of reversing the myofibroblast transdifferentiation of TMCs as a new target for treating GIG.


Assuntos
Transdiferenciação Celular , Dexametasona , Glaucoma , Miofibroblastos , Fatores de Troca de Nucleotídeo Guanina Rho , Malha Trabecular , Dexametasona/farmacologia , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/metabolismo , Malha Trabecular/citologia , Transdiferenciação Celular/efeitos dos fármacos , Animais , Humanos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Miofibroblastos/citologia , Camundongos , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Fatores de Troca de Nucleotídeo Guanina Rho/genética , Glaucoma/patologia , Glaucoma/metabolismo , Células Cultivadas , Glucocorticoides/farmacologia , Camundongos Endogâmicos C57BL , Masculino
17.
Sci Data ; 11(1): 832, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090119

RESUMO

Fractional tree cover facilitates the depiction of forest density and its changes. However, it remains challenging to estimate tree cover from satellite data, leading to substantial uncertainties in forest cover changes analysis. This paper generated a global annual fractional tree cover dataset from 2000 to 2021 with 250 m resolution (GLOBMAP FTC). MODIS annual observations were realigned at the pixel level to a common phenology and used to extract twelve features that can differentiate between trees and herbaceous vegetation, which greatly reduced feature dimensionality. A massive training data, consisting of 465.88 million sample points from four high-resolution global forest cover products, was collected to train a feedforward neural network model to predict tree cover. Compared with the validation datasets derived from the USGS circa 2010 global land cover reference dataset, the R2 value, MAE, and RMSE were 0.73, 10.55%, and 17.98%, respectively. This dataset can be applied for assessment of forest cover changes, including both abrupt forest loss and gradual forest gain.


Assuntos
Florestas , Estações do Ano , Árvores , Redes Neurais de Computação , Imagens de Satélites
18.
Biomol Ther (Seoul) ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39091238

RESUMO

Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-ß/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.

19.
J Clin Invest ; 134(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-39133578

RESUMO

Although cancer has long been considered a genetic disease, increasing evidence shows that epigenetic aberrations play a crucial role in affecting tumor biology and therapeutic response. The dysregulated epigenome in cancer cells reprograms the immune landscape within the tumor microenvironment, thereby hindering antitumor immunity, promoting tumor progression, and inducing immunotherapy resistance. Targeting epigenetically mediated tumor-immune crosstalk is an emerging strategy to inhibit tumor progression and circumvent the limitations of current immunotherapies, including immune checkpoint inhibitors. In this Review, we discuss the mechanisms by which epigenetic aberrations regulate tumor-immune interactions and how epigenetically targeted therapies inhibit tumor progression and synergize with immunotherapy.


Assuntos
Epigênese Genética , Imunoterapia , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/terapia , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Animais , Regulação Neoplásica da Expressão Gênica
20.
NMR Biomed ; : e5238, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134479

RESUMO

Dimethyl sulfoxide (DMSO) has wide biomedical applications such as cryoprotectant and hydrophobic drug carrier. Here, we report for the first time that DMSO can generate a distinctive chemical exchange saturation transfer (CEST) signal at around -2 ppm. Structural analogs of DMSO, including aprotic and protic solvents, also demonstrated CEST signals from -1.4 to -3.8 ppm. When CEST detectable barbituric acid (BA) was dissolved in DMSO solution and was co-loaded to liposome, two obvious peaks at 5 and -2 ppm were observed, indicating that DMSO and related solvent system can be monitored in a label-free manner via CEST, which can be further applied to imaging drug nanocarriers. With reference to previous studies, there could be molecular interactions or magnetization transfer pathways, such as the relayed nuclear Overhauser enhancement (rNOE), that lead to this detectable CEST contrast at negative offset frequencies of the Z-spectrum. Our findings suggest that small molecules of organic solvents could be involved in magnetization transfer processes with water and readily detected by CEST magnetic resonance imaging (MRI), providing a new avenue for detecting solvent-water and solvent-drug interactions.

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