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The on-demand assembly of 2D heterostructures has brought about both novel interfacial physical chemistry and optoelectronic applications; however, existing studies rarely focus on the complementary part-the 2D cavity, which is a new-born area with unprecedented opportunities. In this study, we have investigated the electric field inside a spacer-free 2D cavity consisting of a monolayer semiconductor and a gold film substrate. We have directly captured the built-in electric field crossing a blinking 2D cavity using a Kelvin probe force microscopy-Raman system. The simultaneously recorded morphology (M), electric field (E), and optical spectroscopy (O) mapping profile unambiguously reveals dynamical fluctuations of the interfacial electric field under a constant cavity height. Moreover, we have also prepared non-blinking 2D cavities and analyzed the gap-dependent electric field evolution with a gradual heating procedure, which further enhances the maximum electric field exceeding 109 V/m. Our work has revealed substantial insights into the built-in electric field within a 2D cavity, which will benefit adventures in electric-field-dependent interfacial sciences and future applications of 2D chemical nanoreactors.
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OBJECTIVE: To systematically evaluate the evidence relating to acupuncture on the sleep quality of patients with Parkinson's disease. DATA SOURCES: Six English-language (PubMed, Cochrane Library, EBSCOhost, Embase, OVID MEDLINE, and Web of Science) and four Chinese-language (China National Knowledge Infrastructure, SinoMed, China Scientific Journals Database, and Wanfang) databases were searched for pertinent studies published from database inception to 11 October 2023. METHODS: Two researchers independently screened eligible studies and extracted relevant data using custom data extraction tables. Methodological quality assessment of the included studies was performed using Cochrane Handbook 5.1.0. Meta-analysis was performed using Cochrane Review Manager version 5.4. RESULTS: Twenty-four studies (1701 participants) met inclusion criteria. The meta-analysis showed that acupuncture improved the Parkinson's Disease Sleep Scale, Pittsburgh Sleep Quality Index, Hamilton Anxiety Scale, Hamilton Depression Scale, Self-Rating Depression Scale, and Parkinson's Disease Questionnaire 39 scores compared with controls (all P < 0.05). CONCLUSION: This review showed that acupuncture improved sleep quality, anxiety and depressive symptoms, and quality of life of patients with Parkinson's disease relative to controls.
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Terapia por Acupuntura , Doença de Parkinson , Humanos , Qualidade do Sono , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Qualidade de Vida , AnsiedadeRESUMO
Although selective singlet and triplet interlayer exciton (IX) emission of transition metal dichalcogenides (TMD) heterostructures can be achieved by applying an electric or magnetic field, the device structure is complex and a low temperature is usually required. Here, we demonstrate a simple all-optical approach to selectively enhance the emission of singlet and triplet IX by selectively coupling singlet or triplet IX of a WS2/WSe2 heterostructure to a SiO2 microsphere cavity. Angle-resolved photoluminescene reveals that the transition dipole of triplet IX is almost along the out-of-plane direction, while singlet IX only has 69% out-of-plane dipole moment contribution. Since the out-of-plane dipole presents a higher Purcell factor within the cavity, we can simultaneously enhance the emission intensity of IX and control the emissive IX species at room temperature in an all-optical route. Importantly, we demonstrate an all-optical valley polarization switch with a record high on/off ratio of 35.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes airflow blockage and breathing-related issues. This chronic disease impacts people worldwide. Substantial evidence supports the use of cognitive behavioral therapy (CBT) to help patients with chronic illnesses cope with worrisome and painful symptoms. However, the impact of CBT on COPD outcomes is less understood. OBJECTIVE: In this study, we systematically summarized the effects of CBT on lung function, anxiety and depressive symptoms, and quality of life of patients with COPD. METHODS: Six English-language and four Chinese-language databases were systematically searched for relevant randomized controlled trials published through April 15, 2023. Studies in which CBT was the only difference in treatment administered to experimental and control groups were included in the review. The studies' risk of bias was evaluated using the Cochrane Criteria. RESULTS: Sixteen studies (1887 participants) were included. The meta-analysis showed that CBT improved the percent-predicted forced expiratory volume in 1 second (FEV1%), forced vital capacity (FVC), FEV1/FVC ratio, maximal voluntary ventilation, peak expiratory flow, treatment compliance, and World Health Organization abbreviated quality of life, Self-rating Anxiety and Depression Scale, and St George's Respiratory Questionnaire scores compared with the control (all p < .05). CONCLUSION: This review demonstrated that CBT improves the lung function, anxiety and depressive symptoms, treatment compliance, and quality of life of patients with COPD and can be used widely in the clinical treatment of this disease.
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Terapia Cognitivo-Comportamental , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/psicologia , Terapia Cognitivo-Comportamental/métodos , Terapia Cognitivo-Comportamental/normas , Qualidade de Vida/psicologiaRESUMO
Genetic changes together with epigenetic modifications such as DNA methylation have been demonstrated to regulate many biological processes and thereby govern the response of organisms to environmental changes. However, how DNA methylation might act cooperatively with gene transcription and thereby mediate the long-term adaptive responses of marine microalgae to global change is virtually unknown. Here we performed a transcriptomic analysis, and a whole-genome bisulfite sequencing, along with phenotypic analysis of a model marine diatom Phaeodactylum tricornutum adapted for 2 years to high CO2 and/or warming conditions. Our results show that the methylated islands (peaks of methylation) mCHH were positively correlated with expression of genes in the subregion of the gene body when the populations were grown under high CO2 or its combination with warming for ~2 years. We further identified the differentially expressed genes (DEGs), and hence the metabolic pathways in which they function, at the transcriptomics level in differentially methylated regions (DMRs). Although DEGs in DMRs contributed only 18-24% of the total DEGs, we found that those DEGs acted cooperatively with DNA methylation and then regulated key processes such as central carbon metabolism, amino acid metabolism, ribosome biogenesis, terpenoid backbone biosynthesis, and degradation of misfolded proteins. Taken together, by integrating transcriptomic, epigenetic, and phenotypic analysis, our study provides evidence for DNA methylation acting cooperatively with gene transcription to contribute to the adaptation of microalgae to global changes.
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Metilação de DNA , Diatomáceas , Diatomáceas/genética , Dióxido de Carbono , Epigênese Genética , TranscriptomaRESUMO
Two-dimensional black phosphorus (2D BP), a novel 2D photoelectric material with excellent near-infrared optical absorption, biocompatibility, and degradability, has shown enormous potential in biomedical field. However, under the action of light, oxygen and water, 2D BP is easily degraded to phosphate and phosphonate. In this work, trastuzumab (Tmab) as a positively charged protein was used to modify 2D BP through electrostatic interaction to form BP-Tmab. The Tmab layer on the surface of 2D BP can effectively protect BP from water, which significantly enhanced the water stability of BP. PEGylated 2D BP (BP-PEG) as a control was also prepared. After 7 days in air-exposed water, the attenuation value of BP-Tmab was only 6.62 ± 2.72% at room temperature, which was much lower than that of naked 2D BP (52.47 ± 2.26%) and BP-PEG (25.84 ± 2.80%) under the same conditions. The result was further confirmed by the temperature changes at different time points under laser irradiation, suggesting that the degradation of BP was effectively reduced by Tmab modification. In addition, BP-Tmab displayed satisfactory biocompatibility and can effectively destroy cancer cells under laser irradiation, showing an excellent photothermal therapy effect.
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Antineoplásicos , Fósforo , Proteínas , Fósforo/química , Proteínas/química , Antineoplásicos/química , Humanos , Linhagem Celular Tumoral , FotoquimioterapiaRESUMO
BACKGROUND: The prevalence of skin diseases among prisoners in Taiwan has rarely been investigated. This study aimed to estimate the prevalence of skin diseases by sex in a sample of prisoners in Taiwan. METHODS: We included 83,048 participants from the National Health Insurance Program. The outcomes were measured using the clinical version of the International Classification of Diseases, Ninth Revision. For prevalence, we presented absolute values as well as percentages. We also conducted an X2 test to assess sex differences and age group differences in the percentages of skin and subcutaneous tissue diseases. RESULTS: The prevalence of skin diseases was 42.25%, higher than that in the general population. The prevalence of skin diseases among male prisoners was higher than that among female prisoners (p < 0.001), and the prevalence of skin diseases among prisoners who were ≤ 40 was higher than that among prisoners who were > 40. Among all cases diagnosed with skin disease, the top three diseases were contact dermatitis and other types of eczema, cellulitis and abscess, pruritus, and related conditions. Male prisoners had a significantly higher prevalence of all types of skin diseases than female prisoners. CONCLUSIONS: Skin diseases are common in prisoners in Taiwan. Therefore, early prevention and appropriate treatment are needed. Male-specific skin products are also needed, given the differences in the prevalence of skin diseases among male and female prisoners.
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Prisioneiros , Dermatopatias , Humanos , Masculino , Feminino , Prisões , Prevalência , Taiwan/epidemiologia , Dermatopatias/epidemiologiaRESUMO
Our study aimed to systematically evaluate the effect of acupuncture in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Literature search of four Chinese databases and six English databases for studies published from the inception of each database to March 1, 2022 and identify relevant studies published in Chinese or English. Related randomized controlled trials of acupuncture for the treatment of OSAHS were included to analyze the efficacy of acupuncture. Two researchers independently reviewed all of the retrieved studies to screen for eligible studies and extract the required relevant data. Included studies were subjected to a methodological quality assessment using the Cochrane Manual 5.1.0, and to a meta-analysis using Cochrane Review Manager version 5.4. A total of 19 studies with 1365 participants were examined. Compared with the control group, the apnea-hypopnea index, lowest oxygen saturation, Epworth Sleepiness Scale, interleukin-6, tumor necrosis factor α, and nuclear factor κ-B indicators all exhibited statistically significant changes. Thus, acupuncture was effective in alleviating the state of hypoxia and sleepiness and reduced the inflammatory response and disease severity among reported patients with OSAHS. Therefore, acupuncture could be widely used in the clinical treatment of OSAHS patients as a complementary strategy and warrants further study.
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Terapia por Acupuntura , Apneia Obstrutiva do Sono , Humanos , Sonolência , Apneia Obstrutiva do Sono/terapia , SíndromeRESUMO
AIM: This study systematically compared the efficacy of various dressings that may prevent facial medical device-related pressure injury (MRDPI) in medical staff during the COVID-19 pandemic. BACKGROUND: During the COVID-19 pandemic, medical staff who are required to wear masks, goggles and other personal protective equipment (PPE) are susceptible to facial MRDPI, which exacerbates working conditions. Dressings can effectively prevent or alleviate MRDPI, but it is unclear which dressings are most effective. DESIGN: A systematic review and network meta-analysis, in accordance with PRISMA. METHODS: A comprehensive literature search was conducted in four English and four Chinese databases to identify relevant studies published up to 8 September 2022. The selected studies were randomised controlled trials, with populations comprising medical staff who wore PPE during the COVID-19 pandemic and included an observation and control group. RESULTS: The network meta-analysis of the 12 selected articles showed that foam dressing, hydrocolloid dressing and petrolatum gauze were better than conventional protection for preventing MRDPI. The surface under the cumulative ranking curve indicated that foam dressing was the best preventative. CONCLUSION: Foam dressing is more effective than other dressings in preventing facial MRDPI in medical staff. When PPE must be worn for many hours, such as during the COVID-19 pandemic, medical staff can use foam dressings to prevent MRDPI. RELEVANCE TO CLINICAL PRACTICE: The results support the use of dressings, especially foam dressings, to prevent MRDPI in healthcare workers. The appropriate dressings are recommended to prevent MRDPI associated with wearing PPE.
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COVID-19 , Úlcera por Pressão , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/prevenção & controle , Metanálise em Rede , Pandemias , Bandagens , Corpo ClínicoRESUMO
The effects of potassium (K) fertilization (KCl, analytically pure; 0, 60, 200, and 400 mg kg-1) on the growth and Mn accumulation of Camellia oleifera in two types of Mn-contaminated soils were investigated. The potential mechanisms underlying the impacts of K fertilization were explored. C. oleifera accumulated high amounts of Mn in both soil conditions. The addition of K fertilizer decreased the soil pH and promoted Mn accumulation in C. oleifera. However, the plant biomass decreased significantly under the high level of K fertilization (400 mg kg-1), and the oxidative stress was stimulated under Mn contamination. But an appropriate concentration of K fertilizer (200 mg kg-1) was necessary for the formation of photosynthesis pigments, nonenzymatic antioxidants and antioxidant enzymes, metabolic processes, and nutrient uptake. Furthermore, when plants supplemented with a low level of K fertilization (200 mg kg-1), the catalase activity in C. oleifera leaves was enhanced to alleviate oxidative stress and protect the plant from Mn contamination. Our study demonstrated that 200 mg kg-1 of K fertilizer has the potential to further enhance the efficiency of Mn phytoremediation by C. oleifera.
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Camellia , Poluentes do Solo/análise , Biodegradação Ambiental , Manganês , Potássio , SoloRESUMO
Scleractinian corals are capable of accumulating polycyclic aromatic hydrocarbons (PAHs) in reef environments; however, the mechanism behind their PAHs tolerance is unknown. This study investigated the occurrence and bioaccumulation of PAHs in coral reef ecosystems and examined the physiological responses induced by PAHs in coral hosts and their algal symbionts, the massive coral Galaxea fascicularis and branching coral Pocillopora damicornis. G. fascicularis had a higher PAHs accumulation capacity than P. damicornis. Both the coral hosts and algal symbionts preferentially accumulated acenaphthene, dibenzo(a,h)anthracene, and benzo(a)pyrene. The accumulated PAHs by G. fascicularis and P. damicornis hosts was accompanied by a reduction in detoxification ability. The accumulated PAHs could induce oxidative stress in P. damicorni hosts, thus G. fascicularis demonstrated a greater tolerance to PAHs compared to P. damicornis. Meanwhile, their algal symbionts had fewer physiological responses to accumulated PAHs than the coral hosts. Negative effects were not observed with benzo(a)pyrene. Taken together, these results suggest massive and branching scleractinian corals have different PAHs bioaccumulation and tolerance mechanisms, and indicate that long-term PAHs pollution could cause significant alterations of community structures in coral reef ecosystems.
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Antozoários , Recifes de Corais , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Animais , Antozoários/fisiologia , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Poluentes Químicos da Água/metabolismo , Bioacumulação , Monitoramento Ambiental , SimbioseRESUMO
Image 1.
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[This corrects the article DOI: 10.1016/j.isci.2023.107647.].
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Piezoelectric poly(vinylidene fluoride) (PVDF) and its copolymers have been widely investigated for applications in wearable electric devices and sensing systems, owing to their intrinsic piezoelectricity and superior flexibility. However, their weak piezoelectricity poses major challenges for practical applications. To overcome these challenges, we propose a two-step synthesis approach to fabricate sandwich-structured piezoelectric films (BaTiO3@PDA/PVDF/BaTiO3@PDA) with significantly enhanced ferroelectric and piezoelectric properties. As compared to pristine PVDF films or conventional 0-3 composite films, a maximum polarization (Pmax) of 11.24 µC/cm2, a remanent polarization (Pr) of 5.83 µC/cm2, and an enhanced piezoelectric coefficient (d33 â¼ 14.6 pC/N) were achieved. Simulation and experimental results have demonstrated that the sandwich structure enhances the ability of composite films to withstand higher poling electric fields in comparison with 0-3 composites. The sandwich-structured piezoelectric films are further integrated into a wireless sensor system with a high force sensitivity of 288 mV/N, demonstrating great potential for movement monitoring applications. This facile approach shows great promise for the large-scale production of composite films with remarkable flexibility, ferroelectricity, and piezoelectricity for wearable sensing devices.
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OBJECTIVES: This study aims to systematically assess the risk factors, the overall strength of association, and evidence quality related to delirium among adults hospitalized with COVID-19. METHODS: A comprehensive search was conducted in thirteen databases from inception to February 10, 2023. The included databases were thoroughly searched, including PubMed, Web of Science, Proquest, Ovid MEDLINE, CINAHL, Scopus, the Cochrane Library, FMRS, Wanfang Database, Chinese Biomedical Database (CBM), China Knowledge Resource Integrated Database (CNKI), Weipu Database (VIP), and Embase. The search was limited to articles published in English and Chinese. The selected studies were screened, data were extracted, and the quality was evaluated using the Newcastle-Ottawa Scale. Meta-analysis was performed using RevMan 5.4 software. The certainty of the evidence was assessed using the GRADE criteria. RESULTS: A total of 22 cohort studies with a sample size of 11,957 individuals were included in the analysis. Among these studies, 20 were of high quality, while the remaining 2 were of moderate quality. The risk factors that showed the strongest association with delirium were prior cognitive impairment (including dementia), mechanical ventilation, and ICU admission. Age, frailty (Clinical Frailty Scale scoreâ¯>â¯5), antipsychotic use, benzodiazepine use, neutrophil-to-lymphocyte ratio, and vasopressor use were identified as moderate risk factors for delirium. According to the GRADE evaluation, ICU admission, benzodiazepine use, neutrophil-to-lymphocyte ratio, and vasopressor use had a high-quality body of evidence, while antipsychotic usage had an intermediate-quality body of evidence. All other risk factors had a low-quality body of evidence. CONCLUSIONS: This systematic review and meta-analysis identified several medium- to high-intensity risk factors for delirium in hospitalized adults with COVID-19. ICU admission, benzodiazepine usage, neutrophil-to-lymphocyte ratio, antipsychotic use, and vasopressor use were associated with delirium and were supported by medium- to high-quality evidence. These findings provide healthcare professionals with an evidence-based basis for managing and treating delirium in hospitalized adults with COVID-19.
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Antipsicóticos , COVID-19 , Delírio , Fragilidade , Humanos , Adulto , Antipsicóticos/uso terapêutico , COVID-19/complicações , Benzodiazepinas/uso terapêutico , Estudos de Coortes , Fatores de RiscoRESUMO
BACKGROUND: Hemophilia A is a rare inherited bleeding disorder caused by mutations in the factor VIII gene. This clotting factor plays an intrinsic role in the blood coagulation pathway. Patients with hemophilia may develop orthopedic manifestations such as hemarthrosis, but multiple malunion of fractures over the knee is rare and difficult to treat. CASE SUMMARY: We report a patient with hemophilia A who developed severe knee osteoarthritis along with fracture malunion and nonunion. Total knee replacement was performed using a custom-made modular hinged knee prosthesis (cemented) equipped with extended distal and proximal stems. At 3 years' follow-up, the patient exhibited excellent clinical function and remained satisfied with the surgical outcome. Surgical intervention was accompanied by rigorous coagulation factor replacement. CONCLUSION: This case highlights various unique scenarios specific to individuals with hemophilia and fracture deformity.
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Lipid metabolism plays a critical role in cancer metastasis. However, the mechanisms through which metastatic genes regulate lipid metabolism remain unclear. Here, we describe a new oncogenic-metabolic feedback loop between the epithelial-mesenchymal transition transcription factor ZEB2 and the key lipid enzyme ACSL4 (long-chain acyl-CoA synthetase 4), resulting in enhanced cellular lipid storage and fatty acid oxidation (FAO) to drive breast cancer metastasis. Functionally, depletion of ZEB2 or ACSL4 significantly reduced lipid droplets (LDs) abundance and cell migration. ACSL4 overexpression rescued the invasive capabilities of the ZEB2 knockdown cells, suggesting that ACSL4 is crucial for ZEB2-mediated metastasis. Mechanistically, ZEB2-activated ACSL4 expression by directly binding to the ACSL4 promoter. ACSL4 binds to and stabilizes ZEB2 by reducing ZEB2 ubiquitination. Notably, ACSL4 not only promotes the intracellular lipogenesis and LDs accumulation but also enhances FAO and adenosine triphosphate production by upregulating the FAO rate-limiting enzyme CPT1A (carnitine palmitoyltransferase 1 isoform A). Finally, we demonstrated that ACSL4 knockdown significantly reduced metastatic lung nodes in vivo. In conclusion, we reveal a novel positive regulatory loop between ZEB2 and ACSL4, which promotes LDs storage to meet the energy needs of breast cancer metastasis, and identify the ZEB2-ACSL4 signaling axis as an attractive therapeutic target for overcoming breast cancer metastasis.
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Neoplasias da Mama , Melanoma , Neoplasias Cutâneas , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Retroalimentação , Metabolismo dos Lipídeos , Linhagem Celular Tumoral , Lipídeos , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismoRESUMO
PHARMACOLOGICAL RELEVANCE: Indirubin (IR) is a key active ingredient in the traditional Chinese medication QingDai, also called indigo naturalis, which are extensively used in China to treat chronic diseases, such as inflammation and cancer. However, the function of IR in reducing chondrocyte inflammation in osteoarthritis (OA) is still unclear. AIM OF THE STUDY: The aim of this research was to examine how IR inhibits arthritis and to highlight some of its cellular-level processes. MATERIALS AND METHODS: Chondrocytes from the knee joint of C57 mice were gathered and grown for in vitro tests and used to determine the toxicity of IR toward chondrocytes using a CCK8 kit. Chondrocytes were treated with IL-1ß and IR or with IL-1ß alone, and western blotting was used to determine the expression levels of inflammatory mediators. Meanwhile, through the identification and examination of pertinent markers via quantitative PCR. By using PCR assays, western blotting, toluidine blue staining and safranin O staining, the expression of proteoglycan (AGG) and type II collagen (collagen II) was investigated. Furthermore, western blotting was used to detect activation of the NF-κB and MAPK signaling pathways, and immunofluorescence was used to detect p65 nuclear translocation. In an in vivo experiment, C57BL/6 mice were subjected to destabilization of the medial meniscus (DMM) surgery to produce an OA model, and IR was injected into the articular cavity for 8 weeks. Eventually, the mice were killed, and samples of the knee joints were obtained for histological examination and analysis. RESULTS: IR significantly reduced the expression of inflammatory regulators in chondrocytes treated with IL-1ß, including iNOS and COX-2. Inhibition of IL-1ß induced production of the key catabolic enzymes MMP3, MMP13 and A5. Additionally, an improvement in the downregulation of collagen II and AGG expression was observed. Moreover, IR prevented the aberrant IL-1ß-induced activation of the NF-κB and MAPK signaling pathways, which resulted in downregulation of p65 and p38 expression. Compared to the DMM group, the severity of cartilage injury in animals was dramatically lessened and OARSI scores were lower in the treated groups. CONCLUSION: According to the above findings, IR is quite effective in preventing arthritis both in vivo and in vitro, suggesting that IR may be employed as a possible anti-arthritis drug.
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Condrócitos , Osteoartrite , Camundongos , Animais , NF-kappa B/metabolismo , Transdução de Sinais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Camundongos Endogâmicos C57BL , Osteoartrite/metabolismo , Inflamação/tratamento farmacológico , Articulação do Joelho/patologia , Colágeno/metabolismo , Interleucina-1beta/metabolismo , Células CultivadasRESUMO
AIMS: Hemophilic arthropathy (HA) is a typically iron overload induced joint disease secondary to continuous joint bleeding, however, the exact role of iron chelators in HA has not been fully elucidated. In the present study, we investigated whether desferoxamine (DFO), an iron chelator, could limit the development of HA and the underlying mechanisms. MATERIALS AND METHODS: A HA mice model was established by needle puncture in the left knees of FVIII-deficient hemophilic mice. HA progression was evaluated at 8 weeks after DFO administration. Moreover, chondrocytes were treated with ferric ammonium citrate (FAC) to mimic iron overload in vitro. Modulating effect of DFO on iron overload induced oxidative stress, chondrocytes apoptosis and extracellular matrix (ECM) degradation and the role of HIF-1α-BNIP3 mediated mitophagy were examined. KEY FINDINGS: We found that DFO limited the development of HA and protected iron overload induced ECM degradation, chondrocytes apoptosis and oxidative stress. Besides chelating Fe2+, we found that HIF-1α-BNIP3 mediated mitophagy played important roles in the protective effect of DFO. HIF-1α inhibition suppressed chondrocytes mitophagy process and partly diminished the protective effect of DFO on chondrocytes iron overload. SIGNIFICANCE: In conclusion, DFO could protect against HA development via HIF-1α-BNIP3 mediated mitophagy, suggesting DFO might be a potential therapeutic supplement for HA treatment.
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Sobrecarga de Ferro , Artropatias , Camundongos , Animais , Regulação para Cima , Mitofagia , Quelantes de Ferro/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Sobrecarga de Ferro/tratamento farmacológico , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismoRESUMO
Osteoarthritis (OA) is a prevalent degenerative disease of the elderly. The NRF2 antioxidant system plays a critical role in maintaining redox balance. Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant. This research aimed to determine whether MitoQ alleviated OA and the role of the NRF2/Parkin axis in MitoQ-mediated protective effects. In interleukin (IL)-1ß-induced OA chondrocytes, MitoQ activated the NRF2 pathway, reducing extracellular matrix (ECM) degradation and inflammation. MitoQ also increased glutathione peroxidase 4 (GPX4) expression, leading to decreased levels of reactive oxygen species (ROS) and lipid ROS. Silencing NRF2 weakened MitoQ's protective effects, while knockdown of Parkin upregulated the NRF2 pathway, inhibiting OA progression. Intra-articular injection of MitoQ mitigated cartilage destruction in destabilized medial meniscus (DMM)-induced OA mice. Our study demonstrates that MitoQ maintains cartilage homeostasis in vivo and in vitro through the NRF2/Parkin axis. We supplemented the negative feedback regulation mechanism between NRF2 and Parkin. These findings highlight the therapeutic potential of MitoQ for OA treatment.