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1.
Nat Commun ; 15(1): 3505, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664383

RESUMO

The development of optoelectronics mimicking the functions of the biological nervous system is important to artificial intelligence. This work demonstrates an optoelectronic, artificial, afferent-nerve strategy based on memory-electroluminescence spikes, which can realize multiple action-potentials combination through a single optical channel. The memory-electroluminescence spikes have diverse morphologies due to their history-dependent characteristics and can be used to encode distributed sensor signals. As the key to successful functioning of the optoelectronic, artificial afferent nerve, a driving mode for light-emitting diodes, namely, the non-carrier injection mode, is proposed, allowing it to drive nanoscale light-emitting diodes to generate a memory-electroluminescence spikes that has multiple sub-peaks. Moreover, multiplexing of the spikes can be obtained by using optical signals with different wavelengths, allowing for a large signal bandwidth, and the multiple action-potentials transmission process in afferent nerves can be demonstrated. Finally, sensor-position recognition with the bio-inspired afferent nerve is developed and shown to have a high recognition accuracy of 98.88%. This work demonstrates a strategy for mimicking biological afferent nerves and offers insights into the construction of artificial perception systems.


Assuntos
Potenciais de Ação , Potenciais de Ação/fisiologia , Luminescência , Neurônios Aferentes/fisiologia , Inteligência Artificial , Humanos , Biomimética/métodos
2.
Eur Rev Aging Phys Act ; 21(1): 6, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459483

RESUMO

BACKGROUND: Physical activity (PA) behaviours and comorbid diseases are associated with muscle strength. However, the association between dynapenia and detailed PA behaviours, including participation in aerobic and resistance exercises and sedentary behaviour (SB), in relation to comorbid diseases has not yet been investigated. Using nationwide data, this study aimed to evaluate the independent association of dynapenia with detailed PA behaviour (participation in aerobic and resistance exercises and SB), and assess the differential associations of detailed PA behaviour with dynapenia according to comorbid diseases with prevalent sarcopenia. METHODS: A total of 7,558 community-dwelling older adults aged ≥ 65 years who were included in the Korea National Health and Nutrition Examination Survey from 2014 to 2019 were included in the present study. Cross-sectional associations between PA behaviours (participation in aerobic exercise, participation in resistance exercise, and SB) and dynapenia were analysed using complex-sample multivariable-adjusted logistic regression models according to the type of comorbid disease (cardiovascular disease [CVD], diabetes mellitus [DM], and chronic lung disease [CLD]). RESULTS: Sufficient aerobic exercise, sufficient resistance exercise, and low sedentary time of < 420 min/day showed independent negative associations with dynapenia (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.60-0.83; OR, 0.54; 95% CI, 0.42-0.69; and OR, 0.84; 95% CI, 0.72-0.97, respectively). Among the participants with CVD or CLD, the associations of sufficient resistance exercise (OR, 0.46; 95% CI, 0.26-0.82 and OR, 0.51; 95% CI, 0.35-0.75 for CVD and CLD, respectively) and low sedentary time (OR, 0.66; 95% CI, 0.45-0.98 and OR, 0.71; 95% CI, 0.55-0.93 for CVD and CLD, respectively) with dynapenia were significant, whereas the association of sufficient aerobic exercise with dynapenia was insignificant. Meanwhile, in participants with DM, sufficient aerobic exercise (OR, 0.70; 95% CI, 0.52-0.94) and sufficient resistance exercise (OR, 0.45; 95% CI, 0.29-0.70) were independently associated with dynapenia, whereas no association between SB and dynapenia was found. CONCLUSION: We observed an independent inverse association between PA behaviours and dynapenia. Disease-specific associations between each PA behaviour (sufficient aerobic exercise, sufficient resistance exercise, and low sedentary time) and dynapenia differed in the older adults. Therefore, these differences should be acknowledged during interventions for this population.

3.
Sci Rep ; 14(1): 2396, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514659

RESUMO

Although increased sedentary behavior is associated with poor health outcomes among breast cancer survivors, the factors associated with high sedentary time in community-dwelling breast cancer survivors are unknown. This study aimed to identify factors associated with sedentary behavior in Korean community-dwelling breast cancer survivors aged ≥ 50 years. We included 205 breast cancer survivors from the Korea National Health and Nutrition Examination Survey. Total daily sedentary time was evaluated using questions from the Korean version of the Global Physical Activity Questionnaire. We used complex-sample multivariable-adjusted logistic regression analyses to analyze the associations between sociodemographic factors, medical factors, and health-related quality of life and high sedentary time (≥ 420 min/day). Among the Korean community-dwelling breast cancer survivors, 48.2% had a high daily sedentary time. Insufficient aerobic exercise (OR 2.29; 95% CI 1.12-4.69), diabetes (OR 3.37; 95% CI 1.22-9.33), and unemployed status (OR 2.29; 95% CI 1.05-5.02) were independently associated with high sedentary time after the adjustment for multiple sociodemographic and medical confounders. Participants with a low sedentary time (< 420 min/day) showed a significantly higher mean European Quality of Life 5-Dimensions (EQ-5D) index than those with a high sedentary time after adjusting for multiple confounders (0.89 ± 0.03 vs. 0.82 ± 0.04; P = 0.001). Among the EQ-5D dimensions, problems in mobility (OR 3.37; 95% CI 1.42-7.98) and pain/discomfort (OR 2.64; 95% CI 1.24-5.63) dimensions showed positive associations with high sedentary time. Middle- or older-aged breast cancer survivors with insufficient aerobic exercise, diabetes, unemployed status, and impaired quality of life are more likely to have a high sedentary time. Reducing sedentary behavior in this population requires a tailored approach that considers diverse sociodemographic, medical, and quality-of-life factors.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Diabetes Mellitus , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Comportamento Sedentário , Inquéritos Nutricionais , Qualidade de Vida , Vida Independente
4.
Sci Rep ; 14(1): 6470, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499635

RESUMO

This study develops a solution to sports match-fixing using various machine-learning models to detect match-fixing anomalies, based on betting odds. We use five models to distinguish between normal and abnormal matches: logistic regression (LR), random forest (RF), support vector machine (SVM), the k-nearest neighbor (KNN) classification, and the ensemble model-a model optimized from the previous four. The models classify normal and abnormal matches by learning their patterns using sports betting odds data. The database was developed based on the world football league match betting data of 12 betting companies, which offered a vast collection of data on players, teams, game schedules, and league rankings for football matches. We develop an abnormal match detection model based on the data analysis results of each model, using the match result dividend data. We then use data from real-time matches and apply the five models to construct a system capable of detecting match-fixing in real time. The RF, KNN, and ensemble models recorded a high accuracy, over 92%, whereas the LR and SVM models were approximately 80% accurate. In comparison, previous studies have used a single model to examine football match betting odds data, with an accuracy of 70-80%.


Assuntos
Futebol Americano , Jogo de Azar , Humanos , Modelos Logísticos , Inteligência Artificial
5.
Aging Biol ; 12024.
Artigo em Inglês | MEDLINE | ID: mdl-38500536

RESUMO

There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polß+/-. The 3xTgAD/Polß+/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polß+/- mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38325869

RESUMO

Background: Sarcopenia is common in hemodialysis patients. This study aimed to evaluate the effect of simultaneous nutritional support and intradialytic neuromuscular electrical stimulation (NMES) in hemodialysis patients. Methods: We performed a 12-week, multicenter, randomized controlled trial. The participants were randomly assigned to the control group, the protein group (25 g of protein at every dialysis session), the NMES group (intradialytic NMES to quadriceps femoris muscles), and the NMES + P group (NMES with protein supplementation). The primary outcome was the difference in hand grip strength (HGS) and leg muscle strength (LMS) among groups. Secondary outcomes included body composition, physical performance (the 10-m walk test and the timed up and go test [TUG]), and questionnaires about quality of life (QoL), physical activity, and depression. In addition, subgroup analysis was performed by dividing NMES and NMES + P groups into high- and low-intensity NMES groups. Results: Fifty-nine patients completed all the study outcomes. There was no difference in muscle strength (HGS and LMS) and muscle mass among groups. Gait speed improved in NMES and NMES + P groups. Subscale scores for QoL (kidney disease effect, role limitations due to physical or emotional problems, and overall health ratings) improved in the NMES + P group. In subgroup analysis, LMS and TUG improved only in the high-intensity NMES group. Conclusion: In this study, NMES and-/or- protein supplementation did not make a significant difference in HGS and LMS. However, NMES or NMES + P improved functional capacity and QoL. Furthermore, higher NMES was superior in improving LMS and functional capacity.

7.
Clin Immunol ; 258: 109852, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029848

RESUMO

Atopic dermatitis (AD) treatment has largely relied on non-specific broad immunosuppressants despite their long-term toxicities until the approval of dupilumab, which blocks IL-4 signaling to target Th2 cell responses. Here, we report the discovery of compound 4aa, a novel compound derived from the structure of chlorophyll a, and the efficacy of chlorophyll a to alleviate AD symptoms by oral administration in human AD patients. 4aa downregulated GATA3 and IL-4 in differentiating Th2 cells by potently blocking IL-4 receptor dimerization. In the murine model, oral administration of 4aa reduced the clinical severity of symptoms and scratching behavior by 76% and 72%, respectively. Notably, the elevated serum levels of Th2 cytokines reduced to levels similar to those in the normal group after oral administration of 4aa. Additionally, the toxicological studies showed favorable safety profiles and good tolerance. In conclusion, 4aa may be applied for novel therapeutic developments for patients with AD.


Assuntos
Dermatite Atópica , Humanos , Camundongos , Animais , Dermatite Atópica/tratamento farmacológico , Células Th2 , Clorofila A , Interleucina-4 , Citocinas , Diferenciação Celular
8.
Adv Mater ; 36(3): e2306065, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37560962

RESUMO

Data security is a major concern in digital age, which generally relies on algorithm-based mathematical encryption. Recently, encryption techniques based on physical principles are emerging and being developed, leading to the new generation of encryption moving from mathematics to the intersection of mathematics and physics. Here, device-level encryption with ideal security is ingeniously achieved using modulation of the electron-hole radiative recombination in a GaN-light-emitting diode (LED). When a nano-LED is driven in the non-carrier injection mode, the oscillation of confined electrons can split what should be a single light pulse into multiple pulses. The morphology (amplitude, shape, and pulse number) of those history-dependent multiple pulses that act as carriers for transmitted digital information depends highly on the parameters of the driving signals, which makes those signals mathematically uncrackable and can increase the volume and security of transmitted information. Moreover, a hardware and software platform are designed to demonstrate the encrypted data transmission based on the device-level encryption method, enabling recognition of the entire ASCII code table. The device-level encryption based on splitting electroluminescence provides an encryption method during the conversion process of digital signals to optical signals and can improve the security of LED-based communication.

10.
J Int Med Res ; 51(11): 3000605231213264, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37987669

RESUMO

Campylobacter fetus is a Gram-negative bacillus typically associated with bacteremia in immunocompromised patients. Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve surgery, with a high mortality rate if not treated promptly. We present a rare case of PVE caused by C. fetus. A man in his mid-60s presented to the Emergency Department with a fever and showed elevated C-reactive protein concentrations. He had prosthetic mitral and aortic valve replacement surgery 15 years previously. Gram-negative rods were detected in a blood culture. These rods were identified as C. fetus using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and confirmed by 16S rRNA sequencing. The patient was treated with gentamicin and imipenem, and underwent valve replacement surgery. C. fetus was isolated in a left atrial appendage swab obtained during the surgery. Follow-up blood cultures were negative after treatment. However, after a cardiac arrest event, the patient's general condition deteriorated, and he died. To the best of our knowledge, this is the first case of PVE caused by C. fetus in Korea and the second fatality to date. This case highlights the importance of considering C. fetus as a potential cause of PVE, even in patients without known risk factors.


Assuntos
Endocardite Bacteriana , Próteses Valvulares Cardíacas , Humanos , Masculino , Valva Aórtica/cirurgia , Campylobacter fetus/genética , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , RNA Ribossômico 16S , Idoso
11.
Aging Cell ; 22(9): e13909, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37395319

RESUMO

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.


Assuntos
NAD , Presbiacusia , Humanos , Animais , Camundongos , Receptores Ativados por Proliferador de Peroxissomo , Presbiacusia/tratamento farmacológico , Presbiacusia/prevenção & controle , Cóclea , Suplementos Nutricionais
12.
J Korean Med Sci ; 38(23): e180, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37309699

RESUMO

The personal protective equipment (PPE) used to minimize exposure to hazards can hinder healthcare workers from performing sophisticated procedures. We retrospectively reviewed 77,535 blood cultures (202,012 pairs) performed in 28,502 patients from January 2020 to April 2022. The contamination rate of all blood cultures was significantly elevated in the coronavirus disease 2019 ward at 4.68%, compared to intensive care units at 2.56%, emergency rooms at 1.13%, hematology wards at 1.08%, and general wards at 1.07% (All of P < 0.001). This finding implies that wearing PPE might interfere with adherence to the aseptic technique. Therefore, a new PPE policy is needed that considers the balance between protecting healthcare workers and medical practices.


Assuntos
Hemocultura , COVID-19 , Humanos , Tratamento Farmacológico da COVID-19 , Estudos Retrospectivos , Equipamento de Proteção Individual
13.
Healthcare (Basel) ; 11(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37372885

RESUMO

This study aimed to develop an English version of a doping drug-recognition system using deep learning-based optical character recognition (OCR) technology. A database of 336 banned substances was built based on the World Anti-Doping Agency's International Standard Prohibited List and the Korean Pharmaceutical Information Center's Drug Substance Information. For accuracy and validity analysis, 886 drug substance images, including 152 images of prescriptions and drug substance labels collected using data augmentation, were used. The developed hybrid system, based on the Tesseract OCR model, can be accessed by both a smartphone and website. A total of 5379 words were extracted, and the system showed character recognition errors regarding 91 words, showing high accuracy (98.3%). The system correctly classified all 624 images for acceptable substances, 218 images for banned substances, and incorrectly recognized 44 of the banned substances as acceptable. The validity analysis showed a high level of accuracy (0.95), sensitivity (1.00), and specificity (0.93), suggesting system validity. The system has the potential of allowing athletes who lack knowledge about doping to quickly and accurately check whether they are taking banned substances. It may also serve as an efficient option to support the development of a fair and healthy sports culture.

14.
Blood Transfus ; 21(6): 479-487, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37235735

RESUMO

BACKGROUND: Although blood transfusion is fundamental throughout the course of hematologic malignancies, acute myeloid leukemia (AML) patients requiring intensive chemotherapy are left at the edges of patient blood management programs because current guidelines do not have established recommendations for red blood cell (RBC) transfusion threshold in patients treated for hematological disorders with anemia and accompanied severe thrombocytopenia. To provide answers for the trigger and doses of ideal RBC transfusion in such situation, we conducted this prospective randomized trial. MATERIALS AND METHODS: Newly diagnosed non-acute promyelocytic AML patients undergoing chemotherapy were considered eligible for enrollment. Patients were randomized into 4 groups using a 2 by 2 factorial design, according to the RBC transfusion trigger (hemoglobin [Hb], 7 vs 8 g/dL) and the number of units per transfusion episode (quantity, single vs double-unit). RESULTS: Initially 91 patients were randomized into 4 groups, but the protocol adherence rate was 90.1%. Hb trigger did not affect the amount of RBC transfusion required during treatment. Patients receiving RBC transfusion at Hb <7 g/dL used a median of 4 units of RBC (range 0-12), and those receiving transfusion at Hb <8 g/dL also used a median of 4 units of RBC (range 0-24) (p=0.305). The number of RBC units per transfusion did not affect the total amount of RBC transfusion required during treatment. AML treatment outcomes and bleeding events did not differ across the 4 groups. DISCUSSION: This study demonstrated the feasibility for restrictive RBC transfusion (Hb <7 g/dL, RBC 1 unit) in AML patients undergoing chemotherapy, regardless of chemotherapy intensity.


Assuntos
Anemia , Leucemia Mieloide Aguda , Humanos , Estudos Prospectivos , Projetos Piloto , Hemoglobinas/análise , Leucemia Mieloide Aguda/terapia
15.
Phytomedicine ; 115: 154818, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37187105

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing skin disease accompanied by itchy and dry skin. AD is caused by complex interactions between innate and adaptive immune response. AD treatment include glucocorticoids and immunosuppressants. However, long-term treatment can have serious side effects. Thus, an effective AD treatment with fewer side effects is required. Natural materials, including herbal medicines, have potential applications. PURPOSE: This study evaluated the in vivo and in vitro therapeutic effects of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on AD and investigated the underlying metabolic mechanisms. METHODS: The anti-inflammatory effects of BS012 were assessed using a mouse model of AD induced by 1­chloro-2,4-dinitrobenzene (DNCB) and in tumor necrosis factor-alpha/interferon-gamma (TNF-α/IFN-γ) stimulated normal human epidermal keratinocytes (NHEKs). In DNCB-induced mice, total dermatitis score, histopathological analysis, and immune cell factors were assessed to evaluate the anti-atopic activity. In TNF-α/IFN-γ-stimulated NHEKs, pro-inflammatory cytokines, chemokines, and related signaling pathways were investigated. Serum and intracellular metabolomics were performed to identify the metabolic mechanism underlying the therapeutic effects of BS012 treatment. RESULTS: In DNCB-induced mice, BS012 showed potent anti-atopic activity, including reducing AD-like skin lesions and inhibiting the expression of Th2 cytokines and thymic stromal lymphopoietin. In TNF-α/IFN-γ-stimulated keratinocytes, BS012 dose-dependently inhibited the expression of pro-inflammatory cytokines and chemokines by blocking nuclear factor-kappa B and signal transducer and activator of transcription signaling pathways. Serum metabolic profiles of mice revealed significant changes in lipid metabolism related to inflammation in AD. Intracellular metabolome analysis revealed that BS012 treatment affected the metabolism associated with inflammation, skin barrier function, and lipid organization of the stratum corneum. CONCLUSION: BS012 exerts anti-atopic activity by reducing the Th2-specific inflammatory response and improving skin barrier function in AD in vivo and in vitro. These effects are mainly related to the inhibition of inflammation and recovery of metabolic imbalance in lipid organization. BS012, a novel combination with strong activity in suppressing the Th2-immune response, could be a potential alternative for AD treatment. Furthermore, the metabolic mechanism in vivo and in vitro using a metabolomics approach will provide crucial information for the development of natural products for AD treatment.


Assuntos
Asarum , Cinnamomum aromaticum , Dermatite Atópica , Platycodon , Humanos , Animais , Camundongos , Dermatite Atópica/patologia , Asarum/metabolismo , Cinnamomum aromaticum/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Dinitroclorobenzeno , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Quimiocinas/metabolismo , Interferon gama/metabolismo , Dinitrobenzenos , Lipídeos , Pele/metabolismo , Camundongos Endogâmicos BALB C
16.
Parasites Hosts Dis ; 61(2): 202-209, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37258268

RESUMO

Lophomonas blattarum is an anaerobic protozoan living in the intestine of cockroaches and house dust mites, with ultramicroscopic characteristics such as the presence of a parabasal body, axial filament, and absence of mitochondria. More than 200 cases of Lophomonas infection of the respiratory tract have been reported worldwide. However, the current diagnosis of such infection depends only on light microscopic morphological findings from respiratory secretions. In this study, we attempted to provide more robust evidence of protozoal infection in an immunocompromised patient with atypical pneumonia, positive for Lophomonas-like protozoal cell forms. A direct search of bronchoalveolar lavage fluid via polymerase chain reaction (PCR), transmission electron microscopy (TEM), and metagenomic next-generation sequencing did not prove the presence of protozoal infection. PCR results were not validated with sufficient rigor, while de novo assembly and taxonomic classification results did not confirm the presence of an unidentified pathogen. The TEM results implied that such protozoal forms in light microscopy are actually non-detached ciliated epithelial cells. After ruling out infectious causes, the patient's final diagnosis was drug-induced pneumonitis. These findings underscore the lack of validation in the previously utilized diagnostic methods, and more evidence in the presence of L. blattarum is required to further prove its pathogenicity.


Assuntos
Pneumopatias Parasitárias , Parabasalídeos , Pneumonia por Mycoplasma , Infecções por Protozoários , Humanos , Pneumopatias Parasitárias/diagnóstico , Infecções por Protozoários/diagnóstico , Líquido da Lavagem Broncoalveolar
17.
Free Radic Biol Med ; 203: 34-44, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37011700

RESUMO

Aging is accompanied by a decline in DNA repair efficiency, which leads to the accumulation of different types of DNA damage. Age-associated chronic inflammation and generation of reactive oxygen species exacerbate the aging process and age-related chronic disorders. These inflammatory processes establish conditions that favor accumulation of DNA base damage, especially 8-oxo-7,8 di-hydroguanine (8-oxoG), which in turn contributes to various age associated diseases. 8-oxoG is repaired by 8-oxoG glycosylase1 (OGG1) through the base excision repair (BER) pathway. OGG1 is present in both the cell nucleus and in mitochondria. Mitochondrial OGG1 has been implicated in mitochondrial DNA repair and increased mitochondrial function. Using transgenic mouse models and cell lines that have been engineered to have enhanced expression of mitochondria-targeted OGG1 (mtOGG1), we show that elevated levels of mtOGG1 in mitochondria can reverse aging-associated inflammation and improve functions. Old male mtOGG1Tg mice show decreased inflammation response, decreased TNFα levels and multiple pro-inflammatory cytokines. Moreover, we observe that male mtOGG1Tg mice show resistance to STING activation. Interestingly, female mtOGG1Tg mice did not respond to mtOGG1 overexpression. Further, HMC3 cells expressing mtOGG1 display decreased release of mtDNA into the cytoplasm after lipopolysacchride induction and regulate inflammation through the pSTING pathway. Also, increased mtOGG1 expression reduced LPS-induced loss of mitochondrial functions. These results suggest that mtOGG1 regulates age-associated inflammation by controlling release of mtDNA into the cytoplasm.


Assuntos
DNA Glicosilases , DNA Mitocondrial , Animais , Feminino , Masculino , Camundongos , Dano ao DNA , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Reparo do DNA , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Inflamação/genética , Inflamação/metabolismo , Camundongos Transgênicos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Doenças Neuroinflamatórias , Estresse Oxidativo/genética , Humanos
19.
Neurobiol Dis ; 180: 106092, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36948261

RESUMO

RecQ helicase family proteins play vital roles in maintaining genome stability, including DNA replication, recombination, and DNA repair. In human cells, there are five RecQ helicases: RECQL1, Bloom syndrome (BLM), Werner syndrome (WRN), RECQL4, and RECQL5. Dysfunction or absence of RecQ proteins is associated with genetic disorders, tumorigenesis, premature aging, and neurodegeneration. The biochemical and biological roles of RecQ helicases are rather well established, however, there is no systematic study comparing the behavioral changes among various RecQ-deficient mice including consequences of exposure to DNA damage. Here, we investigated the effects of ionizing irradiation (IR) on three RecQ-deficient mouse models (RecQ1, WRN and RecQ4). We find abnormal cognitive behavior in RecQ-deficient mice in the absence of IR. Interestingly, RecQ dysfunction impairs social ability and induces depressive-like behavior in mice after a single exposure to IR, suggesting that RecQ proteins play roles in mood and cognition behavior. Further, transcriptomic and metabolomic analyses revealed significant alterations in RecQ-deficient mice, especially after IR exposure. In particular, pathways related to neuronal and microglial functions, DNA damage repair, cell cycle, and reactive oxygen responses were downregulated in the RecQ4 and WRN mice. In addition, increased DNA damage responses were found in RecQ-deficient mice. Notably, two genes, Aldolase Fructose-Bisphosphate B (Aldob) and NADPH Oxidase 4 (Nox4), were differentially expressed in RecQ-deficient mice. Our findings suggest that RecQ dysfunction contributes to social and depressive-like behaviors in mice, and that aldolase activity may be associated with these changes, representing a potential therapeutic target.


Assuntos
Replicação do DNA , RecQ Helicases , Animais , Humanos , Camundongos , RecQ Helicases/genética , RecQ Helicases/metabolismo , Reparo do DNA , Dano ao DNA , Instabilidade Genômica , Aldeído Liases/genética , Aldeído Liases/metabolismo
20.
Langmuir ; 39(13): 4622-4630, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-36966511

RESUMO

Extremely water-repellent surfaces with low sliding angle (SA) have been obtained with a facile single-step sol-gel strategy via co-condensation of tetraethoxysilane (TEOS) and hexadecyltrimethoxysilane (HDTMS) in basic media with an efficient self-cleaning property. We investigated the effect of the molar ratio of HDTMS and TEOS on the properties of the modified silica-coated poly(ethylene terephthalate) (PET) film. A high water contact angle (WCA) of 165° and a low SA of 1.35° were obtained at a molar ratio of 0.125. The dual roughness pattern for the low SA was developed by a one-step coating of the modified silica with a molar ratio of 0.125. The evolution of the surface to the dual roughness pattern by nonequilibrium dynamics depended on the size and shape factor of modified silica. The primitive size and the shape factor of the organosilica with a molar ratio of 0.125 were 70 nm and 0.65, respectively. We also presented a new method to determine the superficial surface friction (ζ) of the superhydrophobic surface. The ζ was a physical parameter that characterized the slip and rolling behavior of water droplets on the superhydrophobic surface along with the equilibrium property WCA and the static frictional property SA.

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