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1.
Cell Mol Immunol ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849539

ABSTRACT

The key role of structural cells in immune modulation has been revealed with the advent of single-cell multiomics, but the underlying mechanism remains poorly understood. Here, we revealed that the transcriptional activation of interferon regulatory factor 1 (IRF1) in response to ionizing radiation, cytotoxic chemicals and SARS-CoV-2 viral infection determines the fate of structural cells and regulates communication between structural and immune cells. Radiation-induced leakage of mtDNA initiates the nuclear translocation of IRF1, enabling it to regulate the transcription of inflammation- and cell death-related genes. Novel posttranslational modification (PTM) sites in the nuclear localization sequence (NLS) of IRF1 were identified. Functional analysis revealed that mutation of the acetylation site and the phosphorylation sites in the NLS blocked the transcriptional activation of IRF1 and reduced cell death in response to ionizing radiation. Mechanistically, reciprocal regulation between the single-stranded DNA sensors SSBP1 and IRF1, which restrains radiation-induced and STING/p300-mediated PTMs of IRF1, was revealed. In addition, genetic deletion or pharmacological inhibition of IRF1 tempered radiation-induced inflammatory cell death, and radiation mitigators also suppressed SARS-CoV-2 NSP-10-mediated activation of IRF1. Thus, we revealed a novel cytoplasm-oriented mechanism of IRF1 activation in structural cells that promotes inflammation and highlighted the potential effectiveness of IRF1 inhibitors against immune disorders.

2.
Anal Methods ; 16(20): 3263-3270, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38738477

ABSTRACT

To detect redox potential evolution during the initial stage of an acute wound, a redox-sensitive SERS-active optical fiber was fabricated by integrating redox-sensitive SERS probes in a hole of an optical fiber. The redox-sensitive SERS-active optical fibers carried redox-sensitive SERS probes into the inside of a wound to sense its redox potential. The laser was transmitted to the redox-sensitive SERS probes in the body by optical fibers, and the SERS signals of the redox-sensitive SERS probes were transferred out of the body by optical fibers to indicate the redox potentials in the wound. The redox-sensitive SERS probes dynamically sensed the redox potential in vivo, and their SERS signals were collected constantly to indicate the redox potentials. The assessments in vivo and in vitro proved the responsiveness of redox-sensitive SERS-active optical fibers. The redox potential evolution during the initial stage of an acute wound with the treatments of different concentrations of glucose was detected to verify the feasibility of redox-sensitive SERS-active optical fibers to dynamically detect redox potentials in vivo. The redox-sensitive SERS-active optical fiber would be a versatile tool to explore the roles of redox potentials in living organisms.


Subject(s)
Optical Fibers , Oxidation-Reduction , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Animals , Wound Healing , Male , Mice
3.
Foods ; 13(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38790739

ABSTRACT

The quality of chrysanthemum tea has a great connection with its variety. Different types of chrysanthemum tea have very different efficacies and functions. Moreover, the discrimination of chrysanthemum tea varieties is a significant issue in the tea industry. Therefore, to correctly and non-destructively categorize chrysanthemum tea samples, this study attempted to design a novel feature extraction method based on the fuzzy set theory and improved direct linear discriminant analysis (IDLDA), called fuzzy IDLDA (FIDLDA), for extracting the discriminant features from the near-infrared (NIR) spectral data of chrysanthemum tea. To start with, a portable NIR spectrometer was used to collect NIR data for five varieties of chrysanthemum tea, totaling 400 samples. Secondly, the raw NIR spectra were processed by four different pretreatment methods to reduce noise and redundant data. Thirdly, NIR data dimensionality reduction was performed by principal component analysis (PCA). Fourthly, feature extraction from the NIR spectra was performed by linear discriminant analysis (LDA), IDLDA, and FIDLDA. Finally, the K-nearest neighbor (KNN) algorithm was applied to evaluate the classification accuracy of the discrimination system. The experimental results show that the discrimination accuracies of LDA, IDLDA, and FIDLDA could reach 87.2%, 94.4%, and 99.2%, respectively. Therefore, the combination of near-infrared spectroscopy and FIDLDA has great application potential and prospects in the field of nondestructive discrimination of chrysanthemum tea varieties.

4.
Adv Healthc Mater ; : e2301985, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38776526

ABSTRACT

Infected diabetic wound (DW) presents a prolonged and challenging healing process within the field of regenerative medicine. The effectiveness of conventional drug therapies is hindered by their limited ability to reach deep tissues and promote adequate wound healing rates. Therefore, there is an imperative to develop drug delivery systems that can penetrate deep tissues while exhibiting multifunctional properties to expedite wound healing. In this study, w e devised a soluble microneedle (MN) patch made of γ-PGA, featuring multiple arrays, which w as loaded with core-shell structured nanoparticles (NPs) known as Ag@MSN@CeO2, to enhance the healing of infected DWs. The NP comprises a cerium dioxide (CeO2) core with anti-inflammatory and antioxidant properties, a mesoporous silica NP (MSN) shell with angiogenic characteristics, and an outermost layer doped with Ag to combat bacterial infections. W e demonstrated that the MN platform loaded with Ag@MSN@CeO2 successfully penetrated deep tissues for effective drug delivery. These MN tips induced the formation of multiple regenerative sites at various points, leading to antibacterial, reactive oxygen species-lowering, macrophage ecological niche-regulating, vascular regeneration-promoting, and collagen deposition-promoting effects, thus significantly expediting the healing process of infected DWs. Considering these findings, the multifunctional MN@Ag@MSN@CeO2 patch exhibits substantial potential for clinical applications in the treatment of infected DW.

5.
Nat Commun ; 15(1): 4591, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816373

ABSTRACT

Bridged chiral biaryls are axially chiral compounds with a medium-sized ring connecting the two arenes. Compared with plentiful methods for the enantioselective synthesis of biaryl compounds, synthetic approaches for this subclass of bridged atropisomers are limited. Here we show an atroposelective synthesis of 1,3-diaxial bridged eight-membered terphenyl atropisomers through an Co/SPDO (spirocyclic pyrrolidine oxazoline)-catalyzed aerobic oxidative coupling/desymmetrization reaction of prochiral phenols. This catalytic desymmetric process is enabled by combination of an earth-abundant Co(OAc)2 and a unique SPDO ligand in the presence of DABCO (1,4-diaza[2.2.2]bicyclooctane). An array of diaxial bridged terphenyls embedded in an azocane can be accessed in high yields (up to 99%) with excellent enantio- (>99% ee) and diastereoselectivities (>20:1 dr).

7.
Genes (Basel) ; 15(5)2024 05 15.
Article in English | MEDLINE | ID: mdl-38790255

ABSTRACT

Cordycepin is the primary active compound of Cordyceps militaris. However, the definitive genetic mechanism governing cordycepin synthesis in fruiting body growth and development remains elusive, necessitating further investigation. This study consists of 64 C. militaris strains collected from northeast China. The high-yielding cordycepin strain CMS19 was selected for the analysis of cordycepin production and the genetic basis of cordycepin anabolism. First, the whole-genome sequencing of CMS19 yielded a final size of 30.96 Mb with 8 contigs and 9781 protein-coding genes. The genome component revealed the presence of four additional secondary metabolite gene clusters compared with other published genomes, suggesting the potential for the production of new natural products. The analyses of evolutionary and genetic differentiation revealed a close relationship between C. militaris and Beauveria bassiana. The population of strains distributed in northeast China exhibited the significant genetic variation. Finally, functional genes associated with cordycepin synthesis were identified using a combination of genomic and transcriptomic analyses. A large number of functional genes associated with energy and purine metabolism were significantly enriched, facilitating the reconstruction of a hypothetical cordycepin metabolic pathway. Therefore, our speculation of the cordycepin metabolism pathway involved 24 genes initiating from the glycolysis and pentose phosphate pathways, progressing through purine metabolism, and culminating in the core region of cordycepin synthesis. These findings could offer fundamental support for scientific utilizations of C. militaris germplasm resources and standardized cultivation for cordycepin production.


Subject(s)
Cordyceps , Deoxyadenosines , Cordyceps/genetics , Cordyceps/metabolism , Cordyceps/growth & development , Deoxyadenosines/biosynthesis , Deoxyadenosines/metabolism , Transcriptome/genetics , Genome, Fungal , Gene Expression Profiling/methods , Genomics/methods , Multigene Family , Gene Expression Regulation, Fungal , Whole Genome Sequencing , Phylogeny
8.
Chem Soc Rev ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722208

ABSTRACT

In the electrocatalytic CO2 reduction reaction (CO2RR), metal catalysts with an oxidation state generally demonstrate more favorable catalytic activity and selectivity than their corresponding metallic counterparts. However, the persistence of oxidative metal sites under reductive potentials is challenging since the transition to metallic states inevitably leads to catalytic degradation. Herein, a thorough review of research on oxidation-state stabilization in the CO2RR is presented, starting from fundamental concepts and highlighting the importance of oxidation state stabilization while revealing the relevance of dynamic oxidation states in product distribution. Subsequently, the functional mechanisms of various oxidation-state protection strategies are explained in detail, and in situ detection techniques are discussed. Finally, the prevailing and prospective challenges associated with oxidation-state protection research are discussed, identifying innovative opportunities for mechanistic insights, technology upgrades, and industrial platforms to enable the commercialization of the CO2RR.

9.
Adv Sci (Weinh) ; : e2306253, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38582510

ABSTRACT

The extensive application of nuclear technology has increased the potential of uncontrolled radiation exposure to the public. Since skin is the largest organ, radiation-induced skin injury remains a serious medical concern. Organisms evolutionally develop distinct strategies to protect against environment insults and the related research may bring novel insights into therapeutics development. Here, 26 increased peptides are identified in skin tissues of frogs (Pelophylax nigromaculatus) exposed to electron beams, among which four promoted the wound healing of irradiated skin in rats. Specifically, radiation-induced frog skin peptide-2 (RIFSP-2), from histone proteolysis exerted membrane permeability property, maintained cellular homeostasis, and reduced pyroptosis of irradiated cells with decreased TBK1 phosphorylation. Subsequently, stearyl-CoA desaturase 1 (SCD1) is identified, a critical enzyme in biogenesis of monounsaturated fatty acids (MUFAs) as a direct target of RIFSP-2 based on streptavidin-biotin system. The lipidomic analysis further assured the restrain of MUFAs biogenesis by RIFSP-2 following radiation. Moreover, the decreased MUFA limited radiation-induced and STING-mediated inflammation response. In addition, genetic depletion or pharmacological inhibition of STING counteracted the decreased pyroptosis by RIFSP-2 and retarded tissue repair process. Altogether, RIFSP-2 restrains radiation-induced activation of SCD1-MUFA-STING axis. Thus, the stress-induced amphibian peptides can be a bountiful source of novel radiation mitigators.

10.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167196, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38653358

ABSTRACT

RNA modification plays important roles in various physiological and pathological process. LAGE3 is a component of EKC/KEOPS complex, which is probably involved in the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs, but its exact role in HCC is less studied. Our study reveals that LAGE3 exhibits upregulated expression in HCC compared with normal hepatocellular tissue. High expression of LAGE3 promotes hepatocellular cell proliferation and migration. Further investigations suggest that the increased expression of LAGE3 cloud lead to upregulated VEGFA secretion and angiogenesis in HCC. The mechanistic study reveals LAGE3 is required for the VEGFA mRNA stability. This research may open new avenues for diagnosis and targeted therapy in HCC.


Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Neovascularization, Pathologic , RNA Stability , RNA, Messenger , Vascular Endothelial Growth Factor A , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Cell Proliferation/genetics , Cell Movement/genetics , Cell Line, Tumor , Male , Female , Angiogenesis
11.
Org Lett ; 26(17): 3498-3502, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38661476

ABSTRACT

A novel ion exchange strategy has been developed to enable the asymmetric construction of axially chiral sulfone-containing styrenes. This approach provides a practical synthesis pathway for various axially chiral sulfone-containing styrenes with good yields, exceptional enantioselectivities, and nearly complete E/Z selectivities. Additionally, the reaction mechanism is elucidated in detail through density functional theory (DFT) calculations.

12.
Exp Mol Med ; 56(5): 1107-1122, 2024 May.
Article in English | MEDLINE | ID: mdl-38689083

ABSTRACT

Genotoxic therapy triggers reactive oxygen species (ROS) production and oxidative tissue injury. S-nitrosylation is a selective and reversible posttranslational modification of protein thiols by nitric oxide (NO), and 5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for NO synthesis. However, the mechanism by which BH4 affects protein S-nitrosylation and ROS generation has not been determined. Here, we showed that ionizing radiation disrupted the structural integrity of BH4 and downregulated GTP cyclohydrolase I (GCH1), which is the rate-limiting enzyme in BH4 biosynthesis, resulting in deficiency in overall protein S-nitrosylation. GCH1-mediated BH4 synthesis significantly reduced radiation-induced ROS production and fueled the global protein S-nitrosylation that was disrupted by radiation. Likewise, GCH1 overexpression or the administration of exogenous BH4 protected against radiation-induced oxidative injury in vitro and in vivo. Conditional pulmonary Gch1 knockout in mice (Gch1fl/fl; Sftpa1-Cre+/- mice) aggravated lung injury following irradiation, whereas Gch1 knock-in mice (Gch1lsl/lsl; Sftpa1-Cre+/- mice) exhibited attenuated radiation-induced pulmonary toxicity. Mechanistically, lactate dehydrogenase (LDHA) mediated ROS generation downstream of the BH4/NO axis, as determined by iodoacetyl tandem mass tag (iodoTMT)-based protein quantification. Notably, S-nitrosylation of LDHA at Cys163 and Cys293 was regulated by BH4 availability and could restrict ROS generation. The loss of S-nitrosylation in LDHA after irradiation increased radiosensitivity. Overall, the results of the present study showed that GCH1-mediated BH4 biosynthesis played a key role in the ROS cascade and radiosensitivity through LDHA S-nitrosylation, identifying novel therapeutic strategies for the treatment of radiation-induced lung injury.


Subject(s)
Biopterins , GTP Cyclohydrolase , Lung Injury , Reactive Oxygen Species , Animals , Biopterins/analogs & derivatives , Biopterins/metabolism , Reactive Oxygen Species/metabolism , Mice , Lung Injury/metabolism , Lung Injury/etiology , GTP Cyclohydrolase/metabolism , GTP Cyclohydrolase/genetics , Humans , Radiation Tolerance/genetics , Lactate Dehydrogenase 5/metabolism , Mice, Knockout , Nitric Oxide/metabolism , L-Lactate Dehydrogenase/metabolism , L-Lactate Dehydrogenase/genetics , Protein Processing, Post-Translational , Radiation, Ionizing
13.
Chemosphere ; 357: 141951, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38626815

ABSTRACT

UV/Fe3+ and persulfate are two promising advanced oxidative degradation systems for in situ remediation of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), yet a lack of comprehensive understanding of the degradation mechanisms. For the first time, we used density functional theory (DFT) to calculate the entire reaction pathways of the degradation of PFOA/PFOS in water by UV/Fe3+ and persulfate. In addition, we have deeply explored the different attack pathways driven by •OH and SO4-•, and found that SO4-• determines PFOA/PFOS to obtain PFOA/PFOS free radicals through single electron transfer to initiate the degradation reaction, while •OH determines the speed of PFOA/PFOS degradation reaction. Both degradation reactions were thermodynamically advantageous and kinetically feasible under calculated conditions. Based on the thermodynamic data, persulfate was found to be more favorable for the advanced oxidative degradation of Perfluorinated compounds (PFCs). Moreover, for SO4-• and •OH co-existing in the persulfate system, pH will affect the presence and concentration of these two types of free radicals, and low pH is not necessary for the degradation of PFOA/PFOS in the persulfate system. These results can considerably advance our understanding of the PFOA/PFOS degradation process in advanced oxidation processes (AOPs), which is driven by •OH and SO4-•. This study provides a DFT calculation process for the mechanism calculation of advanced oxidation degradation of other types of PFCs pollutants, hoping to elucidate the future development of PFCs removal. Further research should focus on determining the advanced oxidation degradation pathways of other types of PFCs, to support the development of computational studies on the advanced oxidation degradation of PFCs.


Subject(s)
Alkanesulfonic Acids , Caprylates , Fluorocarbons , Oxidation-Reduction , Water Pollutants, Chemical , Fluorocarbons/chemistry , Caprylates/chemistry , Kinetics , Water Pollutants, Chemical/chemistry , Alkanesulfonic Acids/chemistry , Ultraviolet Rays , Sulfates/chemistry , Density Functional Theory , Thermodynamics , Environmental Restoration and Remediation/methods , Iron/chemistry
14.
Metabolites ; 14(4)2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38668309

ABSTRACT

In order to explore the regulating role and the physiological and biochemical mechanisms of trans-abscisic acid (hereinafter referred as S-ABA) in the process of rice growth and development under salt stress, we took Chaoyou 1000 and Yuxiangyouzhan as materials and set up three salt concentration treatments, CK0 (Control treatment), N1 (50 mmol L-1 NaCl), and N2 (100 mmol L-1 NaCl), in potted trials; we aimed to study the mechanism of rice's response to salt stress from the perspective of agricultural traits and physiological biochemicals and to improve rice's resistance to salt stress through exogenously applying the regulating technology of S-ABA. The following results were obtained: Under salt stress, the growth of rice was significantly suppressed compared to CK0, exhibiting notable increases in agricultural indicators, photosynthesis efficiency, and the NA+ content of leaves. However, we noted a significant decrease in the K+ content in the leaves, alongside a prominent increase in NA+/K+ and a big increase in MDA (malondialdehyde), H2O2 (hydrogen peroxide), and O2- (superoxide anion). This caused the cytomembrane permeability to deteriorate. By applying S-ABA under salt stress (in comparison with salt treatment), we promoted improvements in agronomic traits, enhanced photosynthesis, reduced the accumulation of NA+ in leaves, increased the K+ content and the activity of antioxidant enzymes, and reduced the active oxygen content, resulting in a sharp decrease in the impact of salt stress on rice's development. The application of S-ABA decreased the endogenous ABA (abscisic acid) content under salt stress treatment but increased the endogenous GA (gibberellin) and IAA (indole acetic acid) contents and maintained the hormonal homeostasis in rice plants. To summarize, salt stress causes damage to rice growth, and the exogenous application of S-ABA can activate the pouring system mechanism of rice, suppress the outbreak of active oxygen, and regulate NA+/K+ balance and hormone homeostasis in the blades, thus relieving the salt stress.

15.
Heliyon ; 10(7): e28593, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38576586

ABSTRACT

Background: Family involvement and comfort are equally important in palliative care. Dignity undertook a new meaning and novel challenges as a result of restrictions on visits and companionship during the pandemic. Family-centered family dignity interventions have been shown to be effective in increasing patients' sense of dignity, increasing levels of hope, and reducing psychological distress; however, the effectiveness in enhancing family adaptability and intimacy in the survivor-caregiver binary and reducing expected grief have been inconclusive. Objectives: The primary objective of this study was to assess the efficacy of family dignity interventions on family adaptability and cohesion. The secondary objective was to explore the effects of the interventions on anticipatory grief and psychological distress, and the lasting effect 1 month after the intervention. Design: A single-blinded, two-arm parallel group, randomized controlled trial was conducted in China. Settings: and methods: Ninety-eight dyads who met the inclusion criteria were randomly assigned to the family dignity intervention (n = 51) or standard palliative care group (n = 47) between June and August 2022. Study outcomes were measured at baseline, immediately post-intervention, and at the 1-month follow-up post-intervention evaluation. Data were analyzed using the Kolmogorov-Smirnov test, chi-square test, Fisher's exact test, independent sample t-test, Wilcoxon rank-sum test, and generalized estimation equations. The Intention-To-Treat analysis was performed for all available data. Results: In comparison to the control group, significant improvements in family adaptability and cohesion and anticipatory grief over post-intervention and 1-month follow-up were demonstrated among the patients in the intervention group. The intervention group of caregivers had significant improvement in anticipatory grief at post-intervention and 1-month follow-up. The level of psychological distress was significantly lower in the intervention group than the control group (p < 0.05) at 1-month follow-up but the differences were not statistically significant at post-intervention. All outcomes showed clear differences from baseline after the intervention and at the 1-month follow-up evaluation but not between post-intervention and at the 1-month follow-up evaluation. Conclusion: This study further verifies the actual effect of family dignity intervention program through randomized controlled trials, and provides a reference for improving the family relationship between advanced cancer patients and their family caregivers, and improving their mental health. The addition of family dignity intervention to standard palliative care greatly increased the adaptability and cohesion between survivors and their families, lessened the anticipatory grief of the survivor-caregiver pair, and relieved caregivers' anxiety and despair. We did not detect a statistically significant difference between post-intervention and the 1-month follow-up evaluation, suggesting that the intervention may have a durable impact at least 1 month.

16.
Radiat Res ; 201(4): 294-303, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38588381

ABSTRACT

Radiation-induced intestinal damage (RIID) is a common side effect of radiotherapy in patients with abdominopelvic malignancies. Gap junctions are special structures consisting of connexins (Cxs). This study aimed to investigate the expression and role of connexins in RIID and underlying mechanism. In this study, a calcein-AM fluorescence probe was used to detect changes in gap junctional intercellular communication in intestinal epithelial IEC-6 cells. Our results show that gap junctional intercellular communication of IEC-6 cells was reduced at 6, 12, 24, and 48 h after irradiation, with the most pronounced effect at 24 h. Western blotting and immunofluorescence results showed that the expression of Cx43, but not other connexins, was reduced in irradiated intestinal epithelial cells. Silencing of Cx43 reduced gap junctional intercellular communication between irradiated intestinal epithelial cells with increased ROS and intracellular Ca2+ levels. Furthermore, knockdown of Cx43 reduced the number of clonal clusters, decreased cell proliferation with increased cytotoxicity and apoptosis. Western blotting results showed that silencing of Cx43 resulted in changed γ-H2AX and PI3K/AKT pathway proteins in irradiated intestinal epithelial cells. Administration of the PI3K/AKT pathway inhibitor LY294002 inhibited the radioprotective effects in Cx43-overexpressing intestinal epithelial cells. Our study demonstrated that Cx43 expression is decreased by ionizing radiation, which facilitates the radioprotection of intestinal epithelial cells.


Subject(s)
Connexin 43 , Proto-Oncogene Proteins c-akt , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Calcium/metabolism , Connexins/metabolism , Connexins/pharmacology , Signal Transduction , Gap Junctions , Cell Communication
17.
Exp Neurol ; 376: 114750, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38492636

ABSTRACT

Nerve injury often leads to severe dysfunction because of the lack of axon regeneration in adult mammal. Intriguingly a series of extracellular vesicles (EVs) have the obvious ability to accelerate the nerve repair. However, the detailed molecular mechanisms to describe that EVs switch neuron from a transmitter to a regenerative state have not been elucidated. This study elucidated the microRNA (miRNA) expression profiles of two types of EVs that promote nerve regeneration. The functions of these miRNAs were screened in vitro. Among the 12 overlapping miRNAs, miR-25-3p was selected for further analysis as it markedly promoted axon regeneration both in vivo and in vitro. Furthermore, knockdown experiments confirmed that PTEN and Klf4, which are the major inhibitors of axon regeneration, were the direct targets of miR-25-3p in dorsal root ganglion (DRG) neurons. The utilization of luciferase reporter assays and functional tests provided evidence that miR-25-3p enhances axon regeneration by targeting Tgif1. Additionally, miR-25-3p upregulated the phosphorylation of Erk. Furthermore, Rapamycin modulated the expression of miR-25-3p in DRG neurons. Finally, the pro-axon regeneration effects of EVs were confirmed by overexpressing miR-25-3p and Tgif1 knockdown in the optic nerve crush model. Thus, the enrichment of miR-25-3p in EVs suggests that it regulates axon regeneration, proving a potential cell-free treatment strategy for nerve injury.


Subject(s)
Axons , Extracellular Vesicles , Ganglia, Spinal , Homeodomain Proteins , MicroRNAs , Nerve Regeneration , Schwann Cells , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Nerve Regeneration/physiology , Nerve Regeneration/genetics , Extracellular Vesicles/metabolism , Axons/physiology , Schwann Cells/metabolism , Ganglia, Spinal/metabolism , Ganglia, Spinal/cytology , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Mice , Skin/metabolism , Kruppel-Like Factor 4 , Mice, Inbred C57BL , Stem Cells/metabolism
18.
Article in English | MEDLINE | ID: mdl-38509342

ABSTRACT

Diabetes currently affects approximately 500 million people worldwide and is one of the most common causes of mortality in the United States. To diagnose and monitor diabetes, finger-prick blood glucose testing has long been used as the clinical gold standard. For diabetes treatment, insulin is typically delivered subcutaneously through cannula-based syringes, pens, or pumps in almost all type 1 diabetic (T1D) patients and some type 2 diabetic (T2D) patients. These painful, invasive approaches can cause non-adherence to glucose testing and insulin therapy. To address these problems, researchers have developed miniaturized blood glucose testing devices as well as microfluidic platforms for non-invasive glucose testing through other body fluids. In addition, glycated hemoglobin (HbA1c), insulin levels, and cellular biomechanics-related metrics have also been considered for microfluidic-based diabetes diagnosis. For the treatment of diabetes, insulin has been delivered transdermally through microdevices, mostly through microneedle array-based, minimally invasive injections. Researchers have also developed microfluidic platforms for oral, intraperitoneal, and inhalation-based delivery of insulin. For T2D patients, metformin, glucagon-like peptide 1 (GLP-1), and GLP-1 receptor agonists have also been delivered using microfluidic technologies. Thus far, clinical studies have been widely performed on microfluidic-based diabetes monitoring, especially glucose sensing, yet technologies for the delivery of insulin and other drugs to diabetic patients with microfluidics are still mostly in the preclinical stage. This article provides a concise review of the role of microfluidic devices in the diagnosis and monitoring of diabetes, as well as the delivery of pharmaceuticals to treat diabetes using microfluidic technologies in the recent literature.

19.
Asia Pac J Oncol Nurs ; 11(4): 100389, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38495641

ABSTRACT

Objective: To explore the factors influencing family resilience in adult patients with acute leukemia undergoing chemotherapy, with the aim of providing a theoretical basis for the development of strategies to strengthen their family resilience. Methods: A descriptive phenomenological qualitative research method was used to select 11 adult acute leukemia chemotherapy patients for semi-structured interviews. Colaizzi 7-step analysis and NVivo 12.0 were used to summarize information and refine themes. Results: The main outcomes consisted of two themes and 11 sub-themes: protective factors for family resilience (positive traits, cognitive restructuring, positive family beliefs, organizational flexibility, clear communication, and social support) and risk factors for family resilience (symptom burden, self-concealment, role overload, economic distress, and social alienation). Conclusions: Health care professionals should pay attention to screening protective and risk factors for family resilience in adult acute leukemia chemotherapy patients, affirming the positive role of internal and external resources available in the family in stressful situations, alleviating patients' negative experiences, and promoting the recovery of family function.

20.
Metabolites ; 14(3)2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38535302

ABSTRACT

A large number of dead seedlings can occur in saline soils, which seriously affects the large-scale cultivation of rice. This study investigated the effects of plant growth regulators (PGRs) and nitrogen application on seedling growth and salt tolerance (Oryza sativa L.), which is of great significance for agricultural production practices. A conventional rice variety, "Huang Huazhan", was selected for this study. Non-salt stress treatments included 0% NaCl (CK treatment), CK + 0.05 g N/pot (N treatment), CK + 40 mg·L-1 5-aminolevulinic acid (5-ALA) (A treatment), and CK + 30 mg·L-1 diethylaminoethyl acetate (DTA-6) (D treatment). Salt stress treatments included 0.3% NaCl (S treatment), N + 0.3% NaCl (NS treatment), A + 0.3% NaCl (AS treatment), and D + 0.3% NaCl (DS treatment). When 3 leaves and 1 heart emerged from the soil, plants were sprayed with DTA-6 and 5-ALA, followed by the application of 0.3% NaCl (w/w) to the soil after 24 h. Seedling morphology and photosynthetic indices, as well as carbohydrate metabolism and key enzyme activities, were determined for each treatment. Our results showed that N, A, and D treatments promoted seedling growth, photosynthesis, carbohydrate levels, and the activities of key enzymes involved in carbon metabolism when compared to the CK treatment. The A treatment had the most significant effect, with increases in aboveground dry weight and net photosynthetic rates (Pn) ranging from 17.74% to 41.02% and 3.61% to 32.60%, respectively. Stomatal limiting values (Ls) significantly decreased from 19.17% to 43.02%. Salt stress significantly inhibited seedling growth. NS, AS, and DS treatments alleviated the morphological and physiological damage of salt stress on seedlings when compared to the S treatment. The AS treatment was the most effective in improving seedling morphology, promoting photosynthesis, increasing carbohydrate levels, and key enzyme activities. After AS treatment, increases in aboveground dry weight, net photosynthetic rate, soluble sugar content, total sucrose synthase, and amylase activities were 17.50% to 50.79%, 11.39% to 98.10%, 20.20% to 80.85%, 21.21% to 33.53%, and 22.17% to 34.19%, respectively, when compared to the S treatment. In summary, foliar sprays of 5-ALA, DTA-6, and additional nitrogen fertilizer enhanced rice seedling growth, increased photosynthesis, lowered Ls values, and improved seedling salt tolerance. Spraying two regulators, 5-ALA and DTA-6, quantitatively increased the effect of nitrogen fertilizer, with comparable effects on NaCl stress regulation. This study provides the basis for efficient agricultural production.

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