ABSTRACT
Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells inĀ vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration inĀ vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both inĀ vitro and inĀ vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Humans , Mice , Autophagy/genetics , Carcinogenesis/genetics , Carcinoma, Hepatocellular/genetics , Cell Transformation, Neoplastic , Liver Neoplasms/genetics , Membrane Proteins , Mice, NudeABSTRACT
BACKGROUND: This systematic review and network meta-analysis aimed to assess the comparative effectiveness and safety profiles of current combination therapies based on androgen deprivation therapy (ADT) for the heterogeneous population of individuals with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: We retrieved pertinent literature from PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov, and international conference databases. The study was registered in the Prospective Register of Systematic Reviews (CRD42023453853) for transparency. RESULTS: Our analysis included 20 RCTs involving 14,995 patients, evaluating 15 ADT-based combinations, including systemic therapies, radiotherapy and surgery. In the overall population, the darolutamide triplet (DARO + docetaxel + ADT) demonstrated comparable overall survival (OS) benefits to prostatectomy/radical local therapy (RLT) plus ADT (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.43-1.57). Additionally, the enzalutamide (ENZ) triplet (ENZ + DOC + ADT) appeared to confer the best progression-free survival (HR, 0.34; 95% CI: 0.27-0.43). Subgroup analysis based on metastatic burden indicated that RLT plus ADT had the best OS performance in patients with low burden, while the DARO triplet was associated with the best OS in patients with high burden. Regarding adverse events (AEs), the addition of certain androgen receptor pathway inhibitor (ARPI) agents to ADT led to an increased incidence of severe AEs, while the addition of DOC to the ARPI doublet did not appear to elevate the exposure-adjusted incidence rates. CONCLUSIONS: Our findings suggest that combined treatments result in better survival outcomes than does ADT alone. In the current landscape of systemic therapy, the significance of local therapy should not be underestimated, and therapeutic decisions should be tailored with meticulous consideration of clinical heterogeneity among patients.
Subject(s)
Androgen Antagonists , Antineoplastic Combined Chemotherapy Protocols , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Androgen Antagonists/administration & dosage , Androgen Antagonists/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzamides , Docetaxel/administration & dosage , Docetaxel/therapeutic use , Neoplasm Metastasis , Network Meta-Analysis , Nitriles/therapeutic use , Nitriles/administration & dosage , Phenylthiohydantoin/therapeutic use , Phenylthiohydantoin/administration & dosage , Phenylthiohydantoin/adverse effects , Progression-Free Survival , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/mortality , Prostatic Neoplasms, Castration-Resistant/pathology , Treatment OutcomeABSTRACT
Achieving high gas selectivity is challenging when dealing with gas pairs of similar size and physiochemical properties. The "molecular trapdoor" mechanism discovered in zeolites holds promise for highly selective gas adsorption separation but faces limitations like constrained pore volume and slow adsorption kinetics. To address these challenges, for the first time, a flexible metal-organic framework (MOF) featuring 1D channels and functioning as a "molecular trapdoor" material is intoduced. Extra-framework anions act as "gate-keeping" groups at the narrowest points of channels, permitting gas admissions via gate opening induced by thermal/pressure stimuli and guest interactions. Different guest molecules induce varied energy barriers for anion movement, enabling gas separation based on distinct threshold temperatures for gas admission. The flexible framework of Pytpy MOFs, featuring swelling structure with rotatable pyridine rings, facilitates faster gas adsorption than zeolite. Analyzing anion properties of Pytpy MOFs reveals a guiding principle for selecting anions to tailor threshold gas admission. This study not only overcomes the kinetic limitations related to gas admission in the "molecular trapdoor" zeolites but also underscores the potential of developing MOFs as molecular trapdoor adsorbents, providing valuable insights for designing ionic MOFs tailored to diverse gas separation applications.
ABSTRACT
Ferroptosis is an emerging non-apoptotic death process, mainly involving lipid peroxidation (LPO) caused by iron accumulation, which is potentially lethal to the intrinsically apoptotic-resistant malignant tumor. However, it is still restricted by the inherent antioxidant systems of tumor cells and the poor efficacy of traditional iron-based ferroptosis initiators. Herein, the study develops a novel ferroptosis-inducing agent based on PEGylated Cu+/Cu2+-doped black phosphorus@polypyrrole heterojunction (BP@CPP), which is constructed by utilizing the phosphate on the surface of BP to chelate Cu ions and initiating subsequent in situ polymerization of pyrrole. As a novel Z-scheme heterojunction, BP@CPP possesses an excellent photocatalytic activity in which the separated electron-hole pairs under laser irradiation endow it with powerful oxidizing and reducing capacities, which synergy with Cu+/Cu2+ self-cycling catalyzing Fenton-like reaction to further strengthen reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, ultimately leading to efficient ferroptosis. Systematic in vitro and in vivo evaluations demonstrate that BP@CPP effectively inhibit tumor growth by inducing desired ferroptosis while maintaining a favorable biosafety in the body. Therefore, the developed BP@CPP-based ferroptosis initiator provides a promising strategy for ferroptosis-like cancer therapy.
Subject(s)
Copper , Ferroptosis , Oxidation-Reduction , Reactive Oxygen Species , Ferroptosis/drug effects , Humans , Reactive Oxygen Species/metabolism , Copper/chemistry , Copper/pharmacology , Animals , Cell Line, Tumor , Polymers/chemistry , Polymers/pharmacology , Pyrroles/chemistry , Pyrroles/pharmacology , Neoplasms/metabolism , Neoplasms/drug therapy , Neoplasms/pathology , Mice , Glutathione/metabolism , Phosphorus/chemistryABSTRACT
Constructing a flexible and chemically stable multifunctional layer for the lithium (Li) metal anodes is a highly effective approach to improve the uneven deposition of Li+ and suppress the dendrite growth. Herein, an organic protecting layer of polythiophene is in situ polymerized on the Li metal via plasma polymerization. Compared with the chemically polymerized thiophene (C-PTh), the plasma polymerized thiophene layer (P-PTh), with a higher Young's modulus of 8.1Ā GPa, shows strong structural stability due to the chemical binding of the polythiophene and Li. Moreover, the nucleophilic CĆ¢ĀĀS bond of polythiophene facilitates the decomposition of Li salts in the electrolytes, promoting the formation of LiF-rich solid electrolyte interface (SEI) layers. The synergetic effect of the rigid LiF as well as the flexible PTh-Li can effectively regulate the uniform Li deposition and suppress the growth of Li dendrites during the repeated stripping-plating, enabling the Li anodes with long-cycling lifespan over 8000Ā h (1Ā mAĀ cm-2, 1 mAhĀ cm-2) and 2500Ā h (10Ā mAĀ cm-2, 10 mAhĀ cm-2). Since the plasma polymerization is facile (5-20Ā min) and environmentally friendly (solvent-free), this work offers a novel and promising strategy for the construction of the forthcoming generation of high-energy-density batteries.
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The regulation of legume-rhizobia symbiosis by microorganisms has obtained considerable interest in recent research, particularly in the common rhizobacteria Bacillus. However, few studies have provided detailed explanations regarding the regulatory mechanisms involved. Here, we investigated the effects of Bacillus (Bac.B) on Bradyrhizobium-soybean (Glycine max) symbiosis and elucidated the underlying ecological mechanisms. We found that two Bradyrhizobium strains (i.e. Bra.Q2 and Bra.D) isolated from nodules significantly promoted nitrogen (N) efficiency of soybean via facilitating nodule formation, thereby enhanced plant growth and yield. However, the intrusion of Bac.B caused a reverse shift in the synergistic efficiency of N2 fixation in the soybean-Bradyrhizobium symbiosis. Biofilm formation and naringenin may be importantin suppression of Bra.Q2 growth regulated by Bac.B. In addition, transcriptome and microbiome analyses revealed that Bra.Q2 and Bac.B might interact to regulateN transport and assimilation, thus influence the bacterial composition related to plant N nutrition in nodules. Also, the metabolisms of secondary metabolites and hormones associated with plant-microbe interaction and growth regulation were modulated by Bra.Q2 and Bac.B coinoculation. Collectively, we demonstrate that Bacillus negatively affects Bradyrhizobium-soybean symbiosis and modulate microbial interactions in the nodule. Our findings highlight a novel Bacillus-based regulation to improve N efficiency and sustainable agricultural development.
Subject(s)
Bacillus , Bradyrhizobium , Glycine max , Nitrogen Fixation , Nitrogen , Symbiosis , Glycine max/microbiology , Glycine max/physiology , Glycine max/metabolism , Symbiosis/physiology , Bradyrhizobium/physiology , Bacillus/physiology , Bacillus/metabolism , Nitrogen/metabolism , Root Nodules, Plant/microbiology , Root Nodules, Plant/metabolism , Rhizobium/physiology , Microbiota/physiologyABSTRACT
The incidence of postoperative myocardial injury remains high as the underlying pathogenesis is still unknown. The dorsal root ganglion (DRG) neurons express transient receptor potential vanilloid 1 (TRPV1) and its downstream effector, calcitonin gene-related peptide (CGRP) participating in transmitting pain signals and cardiac protection. Opioids remain a mainstay therapeutic option for moderate-to-severe pain relief clinically, as a critical component of multimodal postoperative analgesia via intravenous and epidural delivery. Evidence indicates the interaction of opioids and TRPV1 activities in DRG neurons. Here, we verify the potential impairment of myocardial viability by epidural usage of opioids in postoperative analgesia. We found that large dose of epidural morphine (50Ā Āµg) significantly worsened the cardiac performance (+dP/dtmax reduction by 11% and -dP/dtmax elevation by 24%, all PĀ <Ā 0.001), the myocardial infarct size (morphine vs Control, 0.54Ā Ā±Ā 0.09 IS/AAR vs. 0.23Ā Ā±Ā 0.06 IS/AAR, PĀ <Ā 0.001) and reduced CGRP in the myocardium (morphine vs. Control, 9.34Ā Ā±Ā 2.24Ā pg/mg vs. 21.23Ā Ā±Ā 4.32Ā pg/mg, PĀ <Ā 0.001), while induced definite suppression of nociception in the postoperative animals. It was demonstrated that activation of Āµ-opioid receptor (Āµ-OPR) induced desensitization of TRPV1 by attenuating phosphorylation of the channel in the dorsal root ganglion neurons, via inhibiting the accumulation of cAMP. CGRP may attenuated the buildup of ROS and the reduction of mitochondrial membrane potential in cardiomyocytes induced by hypoxia/reoxygenation. The findings of this study indicate that epidurally giving large dose of Āµ-OPR agonist may aggravate myocardial injury by inhibiting the activity of TRPV1/CGRP pathway.
Subject(s)
Analgesics, Opioid , Calcitonin Gene-Related Peptide , Animals , Analgesics, Opioid/toxicity , Calcitonin Gene-Related Peptide/pharmacology , Receptors, Opioid, mu/agonists , Morphine/toxicity , Myocardium/pathology , Pain/drug therapy , Pain/metabolism , Pain/pathology , Myocytes, Cardiac/metabolism , TRPV Cation Channels/metabolism , Ganglia, SpinalABSTRACT
We proposed, a novel, to the best of our knowledge, magnetic field measurement with temperature compensation based on a fiber ring microwave photonic filter (FR-MPF) and a Vernier effect. The sensing head is made up by attaching the fiber Bragg grating (FBG) on the magnetostrictive material. Based on the wavelength division multiplexing, two FR-MPFs with different optical carriers can eliminate the influence of the temperature. The Linear chirped FBG (LCFBG) in the FR can transfer the magnetic field variation to the time delay change as well as the frequency shift. Two FR-MPFs with close free spectral ranges can implement the Vernier effect, which can improve the sensitivity. The experimental results show the sensitivity is 58.3Ć¢ĀĀ kHz/Oe and the magnification factor is 214. The proposed sensor has merits of high resolution, high sensitivity and low cross-sensitivity, which has potential applications requiring high precision detections.
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BACKGROUND: Driven by the complex multifactorial etiopathogenesis of autism spectrum disorder (ASD), a growing interest surrounds the disturbance in folate-dependent one-carbon metabolism (OCM) in the pathology of ASD, whereas the evidence remained inconclusive. OBJECTIVES: The study aims to investigate the association of OCM metabolism and ASD and characterize differential OCM metabolites among children with ASD. METHODS: Plasma OCM metabolites were investigated in 59 children with ASD and 40 neurotypical children using ultra-performance liquid chromatography tandem mass spectrometry technology. Differences (significance level < 0.001) were tested in each OCM metabolite between cases and controls. Multivariable models were also performed after adjusting for covariates. RESULTS: Ten out of 22 examined OCM metabolites were significantly different in children with ASD, compared with neurotypical controls. Specifically, S-adenosylmethionine (SAM), oxidized glutathione (GSSG), and glutathione (GSH) levels were increased, whereas S-adenosylhomocysteine (SAH), choline, glycine, L-serine, cystathionine, L-cysteine, and taurine levels were significantly decreased. Children with ASD showed significantly higher SAM/SAH ratio (3.87 Ā± 0.93 compared with 2.00 Ā± 0.76, P = 0.0001) and lower GSH/GSSG ratio [0.58 (0.46, 0.81) compared with 1.71 (0.93, 2.99)] compared with the neurotypical controls. Potential interactive effects between SAM/SAH ratio, taurine, L-serine, and gastrointestinal syndromes were further observed. CONCLUSIONS: OCM disturbance was observed among children with ASD, particularly in methionine methylation and trans-sulfuration pathways. The findings add valuable insights into the mechanisms underlying ASD and the potential of ameliorating OCM as a promising therapeutic of ASD, which warrant further validation.
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Conventional approaches employing nanopowder particles or deposition photocatalytic nanofilm materials encounter challenges such as performance instability, susceptibility to detachment, and recycling complications in practical photocatalytic scenarios. In this study, a novel fabrication strategy is proposed that uses femtosecond laser direct writing of self-sourced metal to prepare a self-supporting microstructure substrate and combines the hydrothermal method to construct a three-dimensional spatially distributed metal oxide micro/nanostructure. The obtained wurtzite ZnO micro/nanostructure has excellent wetting properties while obtaining a larger specific surface area and can achieve effective adsorption of methyl orange molecules. Moreover, the tight integration of ZnO with the surface interface of the self-sourced metal microstructure substrate will facilitate efficient charge transfer. Simultaneously, it improves the efficiency of light utilization (absorption) and the number of active sites in the photocatalytic process, ultimately leading to excellent photodegradation stability. This result provides an innovative technology solution for achieving efficient semiconductor surface-interface photocatalytic performance and stability.
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BACKGROUND AND OBJECTIVES: Intraoperative bile duct injury is a significant complication in laparoscopic cholecystectomy (LC). Near-infrared fluorescence cholangiography (NIFC) can reduce this complication. Therefore, determining the optimal indocyanine green (ICG) dosage for effective NIFC is crucial. This study aimed to determine the optimal ICG dosage for NIFC. METHODS: This was a prospective, randomized, double-blind clinical trial at a single tertiary referral center, including 195 patients randomly assigned to three groups: lower dose (0.01 mg/BMI) ICG (n = 63), medium dose (0.02 mg/BMI) ICG (n = 68), and higher dose (0.04 mg/BMI) ICG (n = 64). Surgeon satisfaction and detection rates for seven biliary structures were compared among the three dose groups. RESULTS: Demographic parameters did not significantly differ among the groups. The medium dose (72.1%) and higher dose ICG groups (70.3%) exhibited superior visualization of the common hepatic duct compared to the lower dose group (41.3%) (p < 0.001). No differences existed between the medium and higher dose groups. Similar trends were observed for the common bile duct and cystic common bile duct junction. CONCLUSIONS: In patients undergoing fluorescent laparoscopic cholecystectomy, the 0.02 mg/BMI dose of indocyanine green demonstrated better biliary structure detection rates than the 0.01 mg/BMI dose and was non-inferior to the 0.04 mg/BMI dose.
Subject(s)
Cholecystectomy, Laparoscopic , Indocyanine Green , Humans , Indocyanine Green/administration & dosage , Cholecystectomy, Laparoscopic/methods , Double-Blind Method , Female , Male , Prospective Studies , Middle Aged , Cholangiography/methods , Adult , Aged , Coloring Agents/administration & dosage , Bile DuctsABSTRACT
Neutrophils are crucial for defense against numerous infections, and their migration and activations are tightly regulated to prevent collateral tissue damage. We previously performed a neutrophil-specific miRNA overexpression screening and identified several microRNAs, including miR-375, as potent modulators for neutrophil activity. Overexpression of miR-375 decreases neutrophil motility and migration in zebrafish and human neutrophil-like cells. We screened the genes downregulated by miR-375 in zebrafish neutrophils and identified that Cathepsin B (Ctsba) is required for neutrophil motility and chemotaxis upon tail wounding and bacterial infection. Pharmacological inhibition or neutrophil-specific knockout of ctsba significantly decreased the neutrophil chemotaxis in zebrafish and survival upon systemic bacterial infection. Notably, Ctsba knockdown in human neutrophil-like cells also resulted in reduced chemotaxis. Inhibiting integrin receptor function using RGDS rescued the neutrophil migration defects and susceptibility to systemic infection in zebrafish with either miR-375 overexpression or ctsba knockout. Our results demonstrate that miR-375 and its target Ctsba modulate neutrophil activity during tissue injury and bacterial infection in vivo, providing novel insights into neutrophil biology and the overall inflammation process.
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In this study, we identified a newly synthesized compound 7o with potent inhibition on EGFR primary mutants (L858R, Del19) and drug-resistant mutant T790M with nanomolar IC50 values. 7o showed strong antiproliferative effects against EGFR mutant-driven non-small cell lung cancer (NSCLC) cells such as H1975, PC-9 and HCC827, over cells expressing EGFRWT. Molecular docking was performed to investigate the possible binding modes of 7o inside the binding site of EGFRL858R/T790M and EGFRWT. Analysis of cell cycle evidenced that 7o induced cell cycle arrest in G1 phases in the EGFR mutant cells, H1975 and PC-9, which resulted in decreased S-phase populations. Moreover, compound 7o induced cancer cell apoptosis in in vitro assays. In addition, 7o inhibited cellular phosphorylation of EGFR. In vivo, oral administration of 7o caused rapid tumor regression in H1975 xenograft model. Therefore, 7o might deserve further optimization as cancer treatment agent for EGFR mutant-driven NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , ErbB Receptors , Molecular Docking Simulation , Cell Proliferation , Protein Kinase Inhibitors , Mutation , Cell Line, Tumor , Drug Resistance, NeoplasmABSTRACT
(Ā±)-Elodeoidileons A-L (1-12), 12 pairs of previously undescribed filicinic acid based meroterpenoids were isolated from Hypericum elodeoides with unique linear or angular 6/6/6 ring core. Modern spectroscopic techniques, modified Mosher's method and quantum chemical calculations were used to identify the planner structures and configurations of 1-12. Additionally, the potential biosynthetic pathways for 1-12 were anticipated. Moreover, biological activity assessments suggested that 1a, 5a, and 11b could activate RetinoidĀ XĀ receptor-α (RXRα) transcription and enhance the ATP-binding cassette transporter A1 (ABCA1) protein's expression. Fluorescence titration assay suggested that 1a might have a direct interaction with the RXRα-LBD protein, with an estimated Kd value of 5.85Ā ĀµM. Moreover, molecular docking study confirmed the binding of 1a to RXRα and further validated by cellular thermal shift assay (CETSA). Thus, compound 1a may promote Ć-amyloid (AĆ) clearance by targeting RXRα and upregulating the expression of the ABCA1 protein, showing promise as anti-Alzheimer's agent.
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OBJECTIVE: Emerging evidence supports that brain dysfunction may be attributable to environmental factors. This study aims to examine associations of ambient temperature and temperature variability (TV) with seizure incidence in children, which has not been explored. MATERIAL AND METHODS: Data on 2718 outpatient visits due to seizure were collected in Shanghai, China, from 2018 to 2023. Exposure to ambient temperature was estimated at children's residential addresses using spatial-temporal models. A time-stratified case-crossover design with a distributed lag non-linear model (DLNM) was conducted to assess the association between seizure incidence and daily average of ambient temperature over a period of 21 days prior to a case date of disease onset. For a given case date, we selected all dates falling on the same day of the week within the same month as control dates. We calculated a composite index of intra-day and inter-day TV, which was the standard deviation of the daily minimum and maximum temperatures, respectively, over 7 days preceding a case date. We then assessed the association between TV and seizure incidence. Stratified analyses were conducted by age (73.51%Ā <Ā 5 years old and 26.49 %Ā ≥Ā 5 years old), sex (41.83% female), presence of fever (69.72%), and diagnosis of epilepsy (27.63%). RESULTS: We observed inversed J-shaped temperature-response curves. Lower temperatures had a significant and prolonged effect than higher temperatures. Using 20Ā Ā°C (with the minimum effect) as the reference, the cumulative odds ratios (ORs) for over 0-21 days preceding the onset at the 5th percentile of the temperature (3Ā Ā°C) and at the 95th percentile (29Ā Ā°C) were 3.17 (95% CI: 1.77, 5.68) and 1.54 (95% CI: 0.97, 2.44), respectively. In addition, per 1Ā Ā°C increases in TV0-7 was associated with OR of 1.08 (95% CI: 1.01, 1.15). Older children and those experiencing seizure with fever exhibited a higher risk of seizure onset at both lower and higher ambient temperatures. CONCLUSION: Both low and high temperatures can contribute to the morbidity related to pediatric seizure. Lower temperatures, however, exerted a longer period of effect prior to seizure onset than higher temperatures. An increased risk for incident seizure was significantly associated with temperature variability during preceding 7 days.
Subject(s)
Cross-Over Studies , Seizures , Temperature , Humans , Seizures/epidemiology , Female , Male , Child, Preschool , China/epidemiology , Child , Incidence , Nonlinear Dynamics , Infant , Environmental Exposure/adverse effectsABSTRACT
Osteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.
Subject(s)
Extracellular Vesicles , Osteoarthritis , Animals , Mice , Quality of Life , Osteoarthritis/metabolism , Homeostasis , Macrophages/metabolism , Extracellular Vesicles/metabolismABSTRACT
The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.
Subject(s)
Cardiomyopathies , Fibroblasts , Fibrosis , Myofibroblasts , RNA, Circular , Animals , Rats , Cardiomyopathies/genetics , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Cell Differentiation/genetics , Cell Differentiation/physiology , Fibroblasts/metabolism , Fibrosis/genetics , Fibrosis/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Myocytes, Cardiac/metabolism , Myofibroblasts/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
OBJECTIVES: Periodontitis is a common oral disease that is aggravated by occlusal trauma. Fibrin is a protein that participates in blood clotting and is involved in several human diseases. The deposition of fibrin in periodontal tissues can induce periodontitis, while mechanical forces may regulate the degradation of fibrin. Our study investigated how occlusal trauma aggravating periodontitis through regulating the plasminogen/plasmin system and fibrin deposition. MATERIALS AND METHODS: This study included 84 C57BL/6 mice in which periodontitis was induced with or without occlusal trauma. Micro-computed tomography was used to assess bone resorption. Fibrin, fibrinogen, plasminogen, plasmin, tissue plasminogen activator (t-PA), and urokinase plasminogen activator (u-PA) levels were measured using Frazer-Lendrum staining, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, immunofluorescence staining, and immunohistochemistry staining. RESULTS: Occlusal trauma aggravated inflammation and bone resorption. The periodontitis group showed significant fibrin deposition. Occlusal trauma increased fibrin deposition and neutrophil aggregation. The periodontitis with occlusal trauma group had decreased fibrinogen, t-PA, and u-PA expression and plasmin and fibrin degradation product levels, as well as increased plasminogen levels. CONCLUSION: Occlusal trauma promotes excessive fibrin deposition by suppressing the plasminogen/plasmin system, thus exacerbating periodontitis.
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Background: Amyotrophic lateral sclerosis (ALS) is an adult neurodegenerative disorder characterized by progressive muscle weakness and eventual paralysis, for which there is currently no curative treatment. Mainstream medical interventions primarily focus on providing supportive care. However, acupuncture offers promising avenues for alleviating symptoms and enhancing quality of life. Specific acupuncture points are targeted to address bulbar paralysis as well as paralysis affecting the upper and lower extremities. Objective: To investigate the efficacy of electroacupuncture combined with Chinese herbal medicine in delaying disease progression and alleviating symptoms of bulbar paralysis in patients with ALS. Case Presentation: A 51-year-old male presented with a 4-year and 8-month history of weakness in his left arm and both legs, accompanied by muscle cramps and diminished coordination, which had rapidly worsened over the past year. ALS was diagnosed, and the patient was initiated on oral Riluzole (50 mg) and Qidong Huoluo granule, a Chinese herbal compound, administered twice daily. Concurrently, he underwent acupuncture treatment sessions twice weekly for over 8 months. Results: Following acupuncture therapy, the patient experienced gradual stabilization of symptoms, notably improvement in swallowing function. The combination of electroacupuncture and Qidong Huoluo granule resulted in sustained clinical enhancements post-treatment, including improvements in speech, coughing, articulation, and breathing. Conclusion: Electroacupuncture therapy demonstrates the potential to slow disease progression and ameliorate symptoms of bulbar paralysis in ALS patients. However, further robust clinical research is imperative to explain the precise therapeutic role of electroacupuncture in managing this debilitating condition. Continued investigation into the efficacy and safety profile of electroacupuncture holds promise for advancing treatment modalities for ALS.
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Phosphorus (P) and iron (Fe) are two essential mineral nutrients in plant growth. It is widely observed that interactions of P and Fe could influence their availability in soils and affect their homeostasis in plants, which has received significant attention in recent years. This review presents a summary of latest advances in the activation of insoluble Fe-P complexes by soil properties, microorganisms, and plants. Furthermore, we elucidate the physiological and molecular mechanisms underlying how plants adapt to Fe-P interactions. This review also discusses the current limitations and presents potential avenues for promoting sustainable agriculture through the optimization of P and Fe utilization efficiency in crops.