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1.
Brain Res ; : 149095, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38917878

ABSTRACT

BACKGROUND: Abnormally elevated homocysteine (Hcy) is recognized as a biomarker and risk factor for Alzheimer's disease (AD). However, the underlying mechanisms by which Hcy affects AD are still unclear. OBJECTIVES: This study aimed to elucidate the effects and mechanisms by which Hcy affects AD-like pathological changes in the hippocampus through in vivo and in vitro experiments, and to investigate whether folic acid (FA) and S-adenosylmethionine (SAM) supplementation could improve neurodegenerative injuries. METHODS: In vitro experiments hippocampal neurons of rat were treated with Hcy, FA or SAM for 24 h; while the hyperhomocysteinemia (HHcy) in Wistar rats was established by intraperitoneal injection of Hcy, and FA was added to feed. The expression of ß-amyloid (Aß), phosphorylated tau protein, presenilin 1 (PS1) at the protein level and the activity of protein phosphatase 2A (PP2A) were detected, the immunopositive cells for Aß and phosphorylated tau protein in the rat hippocampus were also evaluated by immunohistochemical staining. RESULTS: FA and SAM significantly repressed Hcy-induced AD-like pathological changes in the hippocampus, including the increased tau protein phosphorylation at Ser214, Ser396 and the expression of Aß42. In addition, Hcy-induced PS1 expression increased at the protein level and PP2A activity decreased, while FA and SAM were able to retard that. CONCLUSIONS: The increase in PS1 expression and decrease in PP2A activity may be the mechanisms underlying the Hcy-induced AD-like pathology. FA and SAM significantly repressed the Hcy-induced neurodegenerative injury by modulating PS1 and PP2A methylation levels.

2.
Emerg Infect Dis ; 30(7): 1434-1437, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38916639

ABSTRACT

We investigated Alongshan virus infection in reindeer in northeastern China. We found that 4.8% of the animals were viral RNA-positive, 33.3% tested positive for IgG, and 19.1% displayed neutralizing antibodies. These findings suggest reindeer could serve as sentinel animal species for the epidemiologic surveillance of Alongshan virus infection.


Subject(s)
Antibodies, Viral , Reindeer , Animals , Reindeer/virology , China/epidemiology , Antibodies, Viral/blood , Antibodies, Neutralizing/blood , Bunyaviridae Infections/veterinary , Bunyaviridae Infections/epidemiology , Bunyaviridae Infections/virology , RNA, Viral , Immunoglobulin G/blood
3.
STAR Protoc ; 5(2): 103109, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38829736

ABSTRACT

Based on our hypothesis that myotubes exhibit a bistable response to insulin, here we present a protocol for finely measuring Akt phosphorylation in single myotubes under insulin stimulation. We describe steps to stably express a Förster resonance energy transfer (FRET)-based Akt biosensor in C2C12-derived myotubes and perform single-cell FRET imaging. This protocol highlights its potential for precision medicine in analyzing protein phosphorylation dynamics at the single-cell level. For complete details on the use and execution of this protocol, please refer to Akhtar et al.1.


Subject(s)
Fluorescence Resonance Energy Transfer , Insulin , Muscle Fibers, Skeletal , Fluorescence Resonance Energy Transfer/methods , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/cytology , Insulin/metabolism , Insulin/pharmacology , Animals , Mice , Proto-Oncogene Proteins c-akt/metabolism , Cell Line , Phosphorylation , Single-Cell Analysis/methods , Biosensing Techniques/methods
4.
Huan Jing Ke Xue ; 45(6): 3196-3204, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38897743

ABSTRACT

The Guohe River Basin in Anhui Province was selected as the research area for this study. By collecting surface water, shallow groundwater, and middle-deep groundwater samples, various hydrochemical parameters and stable isotopes of water in different water bodies were analyzed using methods such as the Gibbs diagram, ion ratios, and MixSIAR model to reveal and quantify the transformation relationships between these water bodies. The results indicated that both surface water and groundwater in the study area were predominantly neutral to weakly alkaline. The hydrochemical types of surface water were mainly characterized by Cl·SO4·HCO3-Na and Cl·SO4-Na types, whereas the shallow groundwater exhibited HCO3-Ca·Mg and HCO3-Mg·Na types, and the middle-deep groundwater was of the Cl·HCO3-Na type. The hydrochemical characteristics of various water bodies were influenced by multiple factors such as rock weathering, evaporation concentration, and positive cation exchange. The distribution characteristics of δ18O and δ2H values in surface water and groundwater indicated that atmospheric precipitation was the main water source. The δ18O and δ2H in groundwater were significantly correlated with K+, Na+, Cl-, SO42-, and NO3-. According to the analysis using the MixSIAR model, the contribution of atmospheric precipitation to surface water was 46.5 %, whereas the contribution from shallow groundwater was 53.5 %. The sources of shallow groundwater were identified as atmospheric precipitation (57.4 %) and surface water (42.6 %), and the main source of supply for middle-deep groundwater was lateral flow from upstream groundwater.

5.
Sensors (Basel) ; 24(10)2024 May 12.
Article in English | MEDLINE | ID: mdl-38793930

ABSTRACT

The widespread use of encrypted traffic poses challenges to network management and network security. Traditional machine learning-based methods for encrypted traffic classification no longer meet the demands of management and security. The application of deep learning technology in encrypted traffic classification significantly improves the accuracy of models. This study focuses primarily on encrypted traffic classification in the fields of network analysis and network security. To address the shortcomings of existing deep learning-based encrypted traffic classification methods in terms of computational memory consumption and interpretability, we introduce a Parameter-Efficient Fine-Tuning method for efficiently tuning the parameters of an encrypted traffic classification model. Experimentation is conducted on various classification scenarios, including Tor traffic service classification and malicious traffic classification, using multiple public datasets. Fair comparisons are made with state-of-the-art deep learning model architectures. The results indicate that the proposed method significantly reduces the scale of fine-tuning parameters and computational resource usage while achieving performance comparable to that of the existing best models. Furthermore, we interpret the learning mechanism of encrypted traffic representation in the pre-training model by analyzing the parameters and structure of the model. This comparison validates the hypothesis that the model exhibits hierarchical structure, clear organization, and distinct features.

6.
J Environ Manage ; 361: 121266, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38815423

ABSTRACT

Within the Huaihe River Basin, Guohe River, as its second-largest tributary, serves as a critical water supply source. Recent industrial and agricultural advancements have led to increased trace element contamination, adversely impacting the water quality within Guohe River Basin. Therefore, this study aimed to investigate the distribution characteristics, sources, water quality and risk assessment of trace elements in the surface water, groundwater, and sediments across the basin. The results showed that the spatial distribution of trace elements in the surface water and groundwater of Guohe River Basin was that most of the high concentrations appeared in Qiaocheng District of Bozhou City, the mean concentration of Fe in Guohe River sediments was the highest, the mean concentration of Sb was the lowest. The PMF source analysis results showed that the main source of trace elements in Guohe River Basin was natural geological processes, followed by human activities. The sodium adsorption ratio (SAR) indicated that the surface water samples of Guohe River in two seasons had high sodium and salinity hazards. The water quality index (WQI) showed that surface water and groundwater samples in the northwestern of Guohe River Basin had poor water quality. The results of the risk assessment showed that As and Mn posed great ecological risks to surface water and groundwater, respectively, and that F- was the pollutant with the most potential health risk hazard in the basin. The Geo-accumulation index (Igeo) results showed that Cd, Se and As should be taken seriously as the main contaminants of the sediments in Guohe River Basin. KEYWARDS: Trace elements; Source analysis; Sodium adsorption ratio; Water quality index; Risk assessment; Geo-accumulation index.


Subject(s)
Environmental Monitoring , Groundwater , Rivers , Trace Elements , Water Pollutants, Chemical , Water Quality , Risk Assessment , Rivers/chemistry , Trace Elements/analysis , Groundwater/chemistry , Groundwater/analysis , Water Pollutants, Chemical/analysis , Geologic Sediments/chemistry , Geologic Sediments/analysis , China
7.
Prev Sci ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795235

ABSTRACT

Over a 12-year period, this study examined the effects of the Family Check-Up preventive intervention model on both observed and self-reported parenting behaviors of mothers and fathers as well as how those parenting behaviors were associated with young adult antisocial behavior. Teachers identified 641 early adolescent youth from school settings to be at elevated risk for the development of externalizing behavior and/or substance use. These youth and their families were randomly assigned to the Family Check-Up intervention model (consisting of an adaptive, multi-tiered model of support, including a school-based family resource room, the Family Check-Up, and targeted follow-up services) or a control condition. Using an intent-to-treat approach, the Family Check-Up intervention model positively impacted mothers' observed parenting approximately 5 years later in middle adolescence but was not associated with changes in fathers' observed or self-reported parenting. Mothers' observed adaptive parenting and fathers' self-reported adaptive parenting in middle adolescence were associated with lower risk for young adult antisocial behavior. The cascading effects of brief, family-focused interventions are discussed along with implications for the measurement of parenting in mothers and fathers in the context of preventive intervention trials.

8.
J Marital Fam Ther ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38606606

ABSTRACT

As diversity in the United States increases, marriage and family therapists are encountering more multi-heritage couples in therapy. Recent research shows that around 11% of adults are married to someone from a different racial or ethnic group, rising to 19% among new marriages. Multi-heritage couples encompass inherent differences in race, ethnicity, religion, gender, sexual orientation, national origin, and culture. This article addresses the unique challenges faced by multi-heritage couples in therapy and explores the strengths and weaknesses of existing assessment tools suitable for their needs. The study highlights a limited number of existing tools that are available for therapists working with multi-heritage couples. Consequently, the article suggests future directions to enhance the development of assessment tools tailored to the specific needs of multi-heritage couples.

9.
J Extracell Vesicles ; 13(4): e12434, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38634538

ABSTRACT

Apoptosis releases numerous apoptotic vesicles that regulate processes such as cell proliferation, immunity, and tissue regeneration and repair. Now, it has also emerged as an attractive candidate for biotherapeutics. However, apoptotic vesicles encompass a diverse range of subtypes, and it remains unclear which specific subtypes play a pivotal role. In this study, we successfully isolated different apoptotic vesicle subtypes based on their sizes and characterized them using NTA and TEM techniques, respectively. We compared the functional variances among the distinct subtypes of apoptotic vesicles in terms of stem cell proliferation, migration, and differentiation, as well as for endothelial cell and macrophage function, effectively identifying subtypes that exhibit discernible functional differences. ApoSEV (with diameter <1000 nm) promoted stem cell proliferation, migration, and multi-potent differentiation, and accelerated skin wound healing of diabetes mouse model, while apoBD (with diameter >1000 nm) played the opposite effect on cell function and tissue regeneration. Lastly, employing protein analysis and gene sequencing techniques, we elucidated the intrinsic mechanisms underlying these differences between different subtypes of apoEVs. Collectively, this study identified that apoptotic vesicle subtypes possessed distinct bio-functions in regulating stem cell function and behaviour and modulating tissue regeneration, which primarily attribute to the distinct profiling of protein and mRNA in different subtypes. This comprehensive analysis of specific subtypes of apoEVs would provide novel insights for potential therapeutic applications in cell biology and tissue regeneration.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , Mice , Animals , Mesenchymal Stem Cells/metabolism , Wound Healing/physiology , Cell Differentiation , Cell Proliferation
10.
Article in English | MEDLINE | ID: mdl-38571359

ABSTRACT

BACKGROUND: Cutaneous T-cell Lymphoma (CTCL) is a rare group of non-Hodgkin lymphoma originating from the skin, which is characterized by T-cell lymphoproliferative disorders. Chidamide, a Chinese original antineoplastic agent with independent intellectual property rights, and matrine, an extract of Chinese herbal medicine, both have been reported to exert effects on the treatment of tumors individually. However, chidamide combined with matrine has not been tested for the treatment of CTCL. METHODS: Both HH and Hut78 CTCL cell lines were treated with chidamide (0.4 µmol/L), matrine (0.6 g/L), or chidamide combined with matrine for 24, 48, and 72 h. Cell viability was estimated by MTS assay at each time point. Flow cytometry was then conducted to detect cell apoptosis. The exact mechanism of chidamide combined with matrine on CTCL cells was detected by Western blotting and further validated in xenograft models of NOD/SCID mice. RESULTS AND DISCUSSION: Compared to the single drug, chidamide combined with matrine showed a more significant effect on proliferation inhibition and apoptosis induction on CTCL cells both in vitro and in vivo. The results from the in vitro and in vivo studies suggested that matrine could enhance the anti-tumor effect of chidamide by increasing the protein expression of cleaved caspase- 3 and decreasing the expression of E-cadherin, NF-κB, p-Bad, and Bcl-2 to activate apoptosis. CONCLUSION: Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.

11.
Adv Healthc Mater ; 13(13): e2303511, 2024 05.
Article in English | MEDLINE | ID: mdl-38353398

ABSTRACT

Type 2 diabetes is rapidly emerging as a global public health problem. While blood glucose monitoring has been the primary method of managing diabetes for decades, the increasing global prevalence of the disease suggests that there might be a need to identify additional biomarkers for a more precise early diagnosis. Herein, a microneedle patch based wearable sensor is developed for the purpose of diabetic diagnosis. Utilizing methacrylic acid modified gelatin and polyvinyl alcohol in the fabrication of microneedles has improved their mechanical properties for skin penetration and increased swelling capacity for interstitial fluid extraction, thanks to the double crosslinking mechanism. The fabricated microneedles are further integrated with test paper functionalized with enzyme and dye molecules to detect multiple signature biomarkers of diabetes in vivo through a colorimetric reaction. Such a wearable microneedle patch  holds significant promise for the real-time monitoring of various biomarkers related to chronic diseases and aging.


Subject(s)
Biomarkers , Colorimetry , Needles , Wearable Electronic Devices , Colorimetry/methods , Colorimetry/instrumentation , Biomarkers/analysis , Humans , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/metabolism , Animals , Polyvinyl Alcohol/chemistry , Gelatin/chemistry , Mice
12.
Heliyon ; 10(4): e25947, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38375308

ABSTRACT

Secondary vocational education (SVE) is responsible for cultivating talents with moral and technical skills, receiving widespread attention from scholars and the public. Studying the two attentions can broaden the research perspectives and promote the development of SVE. However, there are the following problems: 1) the public attention and academic attention of SVE cannot be accurately characterized; 2) the relationship between the public attention and academic attention of SVE cannot be clear; 3) the impact of public attention and academic attention on SVE cannot be predicted. To address the above issues, this paper puts forward the PLSH (Pearson correlation-Linear regression, Seasonal autoregressive integrated moving average (SARIMA), and Holt-winters model) framework. It involves four research steps: 1) public attention and academic attention are obtained for SVE; 2) the correlation between them is analyzed and a linear model is developed; 3) the performance of the SARIMA model and Holt-winters model are conducted, and the best model is adopted to predict the public attention; 4) academic attention is predicted using the results from the previous step. The study shows that the PLSH framework can characterize academic and public attention to SVE, effectively reflecting their correlation and predicting their growth trends.

13.
Schizophr Res ; 264: 29-38, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38086110

ABSTRACT

BACKGROUND: The pathophysiological mechanisms of schizophrenia are still unclear. Converging evidence suggests that energy metabolism abnormalities are involved in schizophrenia, and support its role in the pathophysiology of this disease. Lactate plays an important role in energy metabolism. Many studies have reported changes in the levels of lactate in the brain and serum of schizophrenia patients; however, the results from these studies are not consistent. To overcome this limitation, the goal of the present meta-analysis is to analyze the changes in lactate levels in the brain and blood of schizophrenia patients. METHODS: For this systematic review and meta-analysis, we performed a thorough search of relevant literature in the English language, using the MEDLINE, Cochrane, and Embase databases. RESULTS: In the present meta-analysis, 20 studies were scrutinized, including 13 studies on brain lactate levels, which involved 322 schizophrenia patients and 324 healthy individuals as controls. 7 studies on blood lactate levels, involving 234 schizophrenia patients and 238 healthy individuals, were also included. Brain lactate levels were elevated in schizophrenia patients, both in vivo and in post-mortem studies. Nevertheless, blood lactate levels in schizophrenia patients have revealed no statistically significant difference, as compared with control individuals. CONCLUSIONS: In comparison with healthy individuals, schizophrenia patients had higher lactate levels in the brain, rather than in the blood. These findings suggest independent regulatory mechanisms of lactate levels in the brain and peripheral tissues. Abnormal lactate metabolism in the brain may be an important pathological mechanism in schizophrenia.


Subject(s)
Schizophrenia , Humans , Brain , Lactic Acid/metabolism , Research Design
14.
Protein Sci ; 33(1): e4857, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38058248

ABSTRACT

The 3C-like protease (3CLpro ) is crucial to the replication of SARS-CoV-2, the causative agent of COVID-19, and is the target of several successful drugs including Paxlovid and Xocova. Nevertheless, the emergence of viral resistance underlines the need for alternative drug strategies. 3CLpro only functions as a homodimer, making the protein-protein interface an attractive drug target. Dimerization is partly mediated by a conserved glycine at position 11. However, some naturally occurring SARS-CoV-2 sequences contain a serine at this position, potentially disrupting the dimer. We have used concentration-dependent activity assays and mass spectrometry to show that indeed the G11S mutation reduces the stability of the dimer by 600-fold. This helps to set a quantitative benchmark for the minimum potency required of any future protein-protein interaction inhibitors targeting 3CLpro and raises interesting questions regarding how coronaviruses bearing such weakly dimerizing 3CLpro enzymes are capable of replication.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Peptide Hydrolases/genetics , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/genetics , Mutation , Antiviral Agents/chemistry
15.
Dent Mater ; 40(1): 90-101, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37923673

ABSTRACT

OBJECTIVES: Regenerating the periodontium poses a critical challenge in oral medicine. To repair various periodontal defects, it is necessary to adopt a bio-scaffold that provides both the architecture and bioactive cues for local stem cells to migrate, reside, proliferate, and differentiate. The objective of this study is to combine a cell-specific decellularized extracellular matrix (ECM) and a biomimetic electrospinning scaffold to regenerate severely destructed periodontium. METHODS: SEM, water contact angle (WCA), live/dead staining, swelling ratio, tensile test and immune-fluorescent staining were used to define the suitable topography for certain dental stem cells seeding and culturing. Transwell assay, CCK-8, Alizarin Red staining and PCR immune-fluorescent staining were used to determine ideal cell-specific ECM for PDLSCs/BMSCs migration, viability, and oriented differentiation. A biodegradable triple-layered electrospun scaffold (TLS) was fabricated by electrospinning with aligned fibers on both surfaces and a polyporous structure in the middle. The morphology and inter-porous structure of the TLS were characterized by SEM and mercury intrusion porosimetry (MIP). The surface of the TLS was functionalized with cell-specific ECM (Bi-ECM-TLS) through decellularization of the cell sheets cultured on the scaffold. The regenerative outcome of Bi-ECM-TLS was assessed by an in-situ rat periodontal defect model. Micro-CT, HE-staining, Masson's trichome staining, Sirius Red staining and Immunofluorescent staining were used for histological analysis. RESULTS: Aligned Gelatin/PCL fibrous membrane (GPA) was most effective for both PDLSCs and BMSCs in culture with WCA around 50 degrees and better mechanical strength than the rest. MSCs favored the same type of ECM (cell-specific ECM), and their regenerative properties were effectively induced with better chemotaxis, proliferative and differentiating behaviors. TLS characterization showed that TLS possessed aligned-random-aligned structure and inter-porous structure. In a rat model of periodontal defects, the TLS functionalized by BMSC-specific ECM for bone regeneration and PDLSC-specific ECM demonstrated highest BV/TV ratio, best bone structure and ligament fiber orientation and blood vessel formation, suggesting optimal performance in regenerating both alveolar bone and periodontal ligaments over TLS, single-ECM loaded TLS and r-Bi-ECM-TLS. SIGNIFICANCE: This study highlights the importance of combining a cell-specific decellularized ECM and a biomimetic electrospinning scaffold for targeted periodontal tissue regeneration, with potential implications for periodontal tissue engineering and improved patient outcomes.


Subject(s)
Gelatin , Tissue Scaffolds , Humans , Rats , Animals , Tissue Scaffolds/chemistry , Extracellular Matrix/chemistry , Periodontium , Tissue Engineering , Periodontal Ligament , Cell Differentiation
16.
Opt Express ; 31(23): 37802-37817, 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-38017902

ABSTRACT

Quantum entanglement between pairs of remote quantum memories (QMs) is a prerequisite for realizing many applications in quantum networks. Here, we present a heralded protocol for the parallel creation of quantum entanglement among multiple pairs of QMs placed in spatially separated nodes, where each QM, encoding a stationary qubit, couples to an optical cavity and deterministically interacts with single photons. Our protocol utilizes an entangled photon pair encoded in the high-dimensional time-bin degree of freedom to simultaneously entangle multiple QM pairs, and is efficient in terms of reducing the time consumption and photon loss during transmission. Furthermore, our approach can be extended to simultaneously support spatial-temporal multiplexing, as its success is heralded by the detection of single photons. These distinguishing features make our protocol particularly useful for long-distance quantum communication and large-scale quantum networks.

17.
J Dermatolog Treat ; 34(1): 2279899, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38010938

ABSTRACT

Immunoglobulin gamma (IgG) type 4-related disease (IgG4-RD) is a chronic immunologic systemic disorder that could affect multiple organs, which may cause irreversible organ damage or even death. Skin involvement is rare and associated especially with systemic disease. The dermatologist must be equipped to recognize IgG4-RD to prevent delayed identification and treatment. This case reports a very rare case of IgG4-related skin disease (IgG4-RSD) presenting with a generalized angiolymphoid hyperplasia with eosinophilia (ALHE)-like lesions in a middle-aged male patient with no other organ involvement. He was treated with oral glucocorticoid and cyclophosphamide, which resulted in complete remission. No relapse and disease progression were seen with a follow-up for 8 years.


Subject(s)
Angiolymphoid Hyperplasia with Eosinophilia , Immunoglobulin G4-Related Disease , Humans , Male , Middle Aged , Angiolymphoid Hyperplasia with Eosinophilia/pathology , Angiolymphoid Hyperplasia with Eosinophilia/therapy , Cyclophosphamide/therapeutic use , Follow-Up Studies , Glucocorticoids/therapeutic use , Immunoglobulin G , Immunoglobulin G4-Related Disease/complications
18.
Environ Sci Pollut Res Int ; 30(59): 123466-123479, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37987974

ABSTRACT

Groundwater is an essential freshwater resource utilized in industry, agriculture, and daily life. In the Huaibei Plain (HBP), where groundwater significantly influences socio-economic development, information about its quality, hydrochemistry, and related health risks remains limited. We conducted a comprehensive groundwater sampling in the HBP and examined its rock characteristics, water quality index (WQI), and potential health risks. The results revealed that the primary factors shaping groundwater hydrochemistry were rock dissolution and weathering, cation exchange, and anthropogenic activities. WQI assessment indicated that only 73% of the groundwaters is potable, as Fe2+, Mn2+, NO3-, and F- contents in the water could pose non-carcinogenic hazards to humans. Children were more susceptible to these health risks through oral ingestion than adults. Uncertainty analysis indicated that the probabilities of non-carcinogenic risk were approximately 57% and 31% for children and adults, respectively. Sensitivity analysis further identified fluoride as the primary factor influencing non-carcinogenic risks, indicating that reducing fluoride contamination should be prioritized in future groundwater management in the HBP.


Subject(s)
Groundwater , Water Pollutants, Chemical , Child , Adult , Humans , Environmental Monitoring/methods , Fluorides/analysis , Water Pollutants, Chemical/analysis , Water Quality , Groundwater/chemistry , China , Risk Assessment
19.
Int J Nanomedicine ; 18: 6955-6977, 2023.
Article in English | MEDLINE | ID: mdl-38026535

ABSTRACT

Background: Diabetic chronic wounds present a formidable challenge in clinical management, lacking effective treatment options. Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for tissue repair and regeneration. However, transplanted MSCs often undergo rapid apoptosis, giving rise to heterogeneous extracellular vesicles (EVs), including apoptotic bodies (apoBDs) and apoptotic small extracellular vesicles (apoSEVs). The potential stimulatory role of these EVs in diabetic wound healing remains unknown. Methods: In this study, we investigated the effects of apoSEVs derived from adipose-derived mesenchymal/stromal cells (ADSCs) on the recovery of diabetic wounds by modulating the function of versatile target cells. First, we characterized the apoSEVs and apoBDs derived from apoptotic ADSCs. Subsequently, we evaluated the effects of apoSEVs and apoBDs on macrophages, endothelial cells, and fibroblasts, three essential cell types in wound healing, under high-glucose conditions. Furthermore, we developed a gelatin methacryloyl (GelMA) hydrogel for the sustained release of apoSEVs and investigated its therapeutic effects on wound healing in type 2 diabetic mice in vivo. Results: apoSEVs facilitated the polarization of M1 phenotype macrophages to M2 phenotype, promoted proliferation, migration, and tube formation of endothelial cells, and enhanced fibroblast proliferation and migration. However, apoBDs failed to improve the function of endothelial cells and fibroblasts. In vivo, the apoSEVs-loaded GelMA effectively promoted wound healing by facilitating collagen fiber deposition, angiogenesis, and immune regulation. Conclusion: Our study elucidates the beneficial effects of apoSEVs on wound recovery in diabetes and introduces a novel strategy for diabetic wound treatment based on apoSEVs.


Subject(s)
Diabetes Mellitus, Experimental , Mesenchymal Stem Cells , Mice , Animals , Diabetes Mellitus, Experimental/therapy , Diabetes Mellitus, Experimental/metabolism , Endothelial Cells , Wound Healing , Skin , Mesenchymal Stem Cells/metabolism
20.
Int J Mol Sci ; 24(18)2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37762332

ABSTRACT

Innovative therapeutic strategies for esophageal squamous cell carcinoma (ESCC) are urgently required due to the limited effectiveness of standard chemotherapies. C-Terminal Binding Protein 1 (CtBP1) has been implicated in various cancers, including ESCC. However, the precise expression patterns and functional roles of CtBP1 in ESCC remain inadequately characterized. In this study, we aimed to investigate CtBP1 expression and its role in the resistance of ESCC to paclitaxel, an effective chemotherapeutic agent. Western blotting and immunofluorescence were applied to assess CtBP1 expression in the TE-1 and KYSE-50 cell lines. We observed the marked expression of CtBP1, which was associated with enhanced proliferation, invasion, and metastasis in these cell lines. Further, we successfully generated paclitaxel resistant ESCC cell lines and conducted cell viability assays. We employed the CRISPR/Cas9 genome editing system to disable the CtBP1 gene in ESCC cell lines. Through the analysis of the drug dose-response curve, we assessed the sensitivity of these cell lines in different treatment groups. Remarkably, CtBP1-disabled cell lines displayed not only improved sensitivity but also a remarkable inhibition of proliferation, invasion, and metastasis. This demonstrates that CtBP1 may promote ESCC cell malignancy and confer paclitaxel resistance. In summary, our study opens a promising avenue for targeted therapies, revealing the potential of CtBP1 inhibition to enhance the effectiveness of paclitaxel treatment for the personalized management of ESCC.

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