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1.
Microorganisms ; 12(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38543559

RESUMO

Pollutants can exist in the soil for a long time and alter the bacterial community. Using lubricants to prevent the wear of chainsaw blades is necessary for thinning activities and wood harvesting. We investigated the influences of soil contamination with chainsaw lubricants on soil bacterial communities. Bio-oil, mineral oil, and recycled oil were scattered on each treatment to investigate variations in soil bacterial structure during treated periods using the Illumina MiSeq sequencing platform. The results obtained were 5943 ASVs, 5112 ASVs, and 6136 ASVs after treatment at one month, six months, and twelve months, respectively. There was a significant difference in Shannon and Simpson indices between treatments and controls. A total of 46 bacterial genera with an average relative abundance of more than 1.0% were detected in all soil samples. Massilia was the most common genus detected in control at one month, with an average relative abundance of 14.99%, while Chthoniobacter was the most abundant genus detected in bio-oil, mineral oil, and recycled oil treatments at one month, with an average relative abundance of 13.39%, 14.32%, and 10.47%, respectively. Among the three chainsaw lubricants, bio-oil and mineral oil had fewer impacts than recycled oil. The abundances of several functional bacteria groups in the bio-oil treatment were higher than in other treatments and controls. Our results indicated that different chainsaw lubricants and their time of application affected the soil bacterial community composition.

2.
Mitochondrial DNA B Resour ; 8(11): 1187-1191, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37937099

RESUMO

Vanderbylia fraxinea (Bull.) D.A. Reid, 1973 is an important wood-inhabiting fungus that plays a significant role in nutrient recycling in most forest ecosystems. In this study, the complete mitochondrial genome of V. fraxinea was characterized through de novo assembly using Illumina sequencing data and genome annotation. The mitochondrial genome is a circular molecule of 115,473 bp with a GC content of 28.66%. It comprises a total of 62 genes. Among these, 36 are protein-coding genes including 21 free-standing open reading frames (ORFs), 24 transfer RNA genes, and two ribosomal RNA genes. Core gene set commonly found in fungal mitochondrial genomes is also present in this genome, such as the apocytochrome b (cob), three subunits of the cytochrome c oxidase (cox1, cox2, and cox3), seven subunits of the NADH dehydrogenase (nad1, nad2, nad3, nad4, nad4L, nad5, and nad6), and three subunits of the ATP synthase (atp6, atp8, and atp9), as well as ribosomal RNA subunits (rns and rnl) and a set of transfer RNA genes. Phylogenetic analysis of the protein-coding sequences from the mitochondrial genome revealed a close relationship between V. fraxinea and the Ganoderma species within the Polyporaceae family.

3.
Nutrients ; 15(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37836456

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory disease characterized by dry and itchy skin. Recently, it has been reported that oxidative stress is involved in skin diseases, possibly including AD. Vitamin C, also referred to as ascorbic acid, is a vital water-soluble compound that functions as an essential nutrient. It plays a significant role as both an antioxidant and an additive in various pharmaceutical and food products. Despite the fact that vitamin C is easily oxidized, we have developed NXP081, a single-stranded DNA aptamer that selectively binds to vitamin C, thereby inhibiting its oxidation. The objective of the current research was to examine the impact of NXP081, an animal model of AD induced by 2,4-dinitrofluorobenzene (DNFB). The experimental drug NXP081, when taken orally, showed promising results in reducing inflammation and improving the skin conditions caused by DNFB. The administration of NXP081 resulted in a significant reduction in ear swelling and a noticeable improvement in the appearance of skin lesions. In addition, the administration of NXP081 resulted in a significant decrease in the migration of mast cells in the skin lesions induced by DNFB. Moreover, NXP081 inhibited the production of interferon-gamma (IFN-γ) in CD4+ T cells that were activated and derived from the lymph nodes. Our findings provide useful information about the anti-inflammatory effect of NXP081 on AD.


Assuntos
Aptâmeros de Nucleotídeos , Dermatite Atópica , Dermatopatias , Camundongos , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Dinitrofluorbenzeno/efeitos adversos , Camundongos Endogâmicos BALB C , Aptâmeros de Nucleotídeos/efeitos adversos , Ácido Ascórbico/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Dermatopatias/metabolismo , Vitaminas/farmacologia , Pele/metabolismo , Citocinas/metabolismo
4.
Int J Biochem Cell Biol ; 162: 106454, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37574041

RESUMO

Cisplatin, a widely prescribed chemotherapeutic agent for treating solid tumors, induces DNA adducts and activates cellular defense mechanisms, including DNA repair, cell cycle checkpoint control, and apoptosis. Considering the circadian rhythmicity displayed by most chemotherapeutic agents and their varying therapeutic efficacy based on treatment timing, our study aimed to investigate whether the circadian clock system influences the DNA damage responses triggered by cisplatin in synchronized cells. We examined the DNA damage responses in circadian-synchronized wild-type mouse embryonic fibroblasts (WT-MEF; clock-proficient cells), cryptochrome1 and 2 double knock-out MEF (CRYDKO; clock-deficient cells), and mouse hepatocarcinoma Hepa1c1c7 cells. Varying the treatment time resulted in a significant difference in the rate of platinum-DNA adduct removal specifically in circadian-synchronized WT-MEF, while CRYDKO did not exhibit such variation. Moreover, diurnal variation in other DNA damage responses, such as cell cycle checkpoint activity indicated by p53 phosphorylation status and apoptosis measured by DNA break frequency, was observed only in circadian-synchronized WT-MEF, not in CRYDKO or mouse hepatocarcinoma Hepa1c1c7 cells. These findings highlight that the DNA damage responses triggered by cisplatin are indeed governed by circadian control exclusively in clock-proficient cells. This outcome bears potential implications for enhancing or devising chronotherapy approaches for cancer patients.


Assuntos
Relógios Circadianos , Neoplasias , Animais , Camundongos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Adutos de DNA/uso terapêutico , Dano ao DNA , Fibroblastos/metabolismo , Reparo do DNA , Relógios Circadianos/genética , Neoplasias/genética , Apoptose
5.
Sensors (Basel) ; 23(12)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37420824

RESUMO

The vanilla federated learning is made for a trusted environment, while in contrast, its actual use cases require collaborations in an untrusted setting. For this reason, using blockchain as a trusted platform to run federated learning algorithms has gained traction lately and has become a significant research interest. This paper performs a literature survey on state-of-the-art blockchain-based federated learning systems and analyzes several design patterns researchers often take to solve existing issues through blockchain. We find about 31 design item variations throughout the whole system. Each design is further analyzed to find pros and cons, considering fundamental metrics such as robustness, efficiency, privacy, and fairness. The result shows a linear relationship between fairness and robustness in which, if we focus on improving fairness, it will indirectly become more robust. Furthermore, improving all those metrics altogether is not viable because of the efficiency trade-off. Finally, we classify the surveyed papers to spot which designs are popular among researchers and determine which areas require immediate improvements. Our investigation shows that future blockchain-based federated learning systems require more effort regarding model compression, asynchronous aggregation, system efficiency evaluation, and the application for cross-device settings.


Assuntos
Blockchain , Compressão de Dados , Algoritmos , Benchmarking , Privacidade
6.
Sensors (Basel) ; 23(12)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37420938

RESUMO

The authors make the following corrections to the published paper [...].

7.
J Neurol Neurosurg Psychiatry ; 94(10): 800-805, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37268404

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD. METHODS: This multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis. RESULTS: In total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment. CONCLUSIONS: Earlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.


Assuntos
Aquaporinas , Neuromielite Óptica , Pessoa de Meia-Idade , Humanos , Feminino , Adulto , Masculino , Rituximab/uso terapêutico , Estudos Retrospectivos , Autoanticorpos , Aquaporina 4
8.
Front Aging Neurosci ; 15: 1148444, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122380

RESUMO

Objective: Neuronata-R® (lenzumestrocel) is an autologous bone marrow-derived mesenchymal stem cell (BM-MSC) product, which was conditionally approved by the Korean Ministry of Food and Drug Safety (KMFDS, Republic of Korea) in 2013 for the treatment of amyotrophic lateral sclerosis (ALS). In the present study, we aimed to investigate the long-term survival benefits of treatment with intrathecal lenzumestrocel. Methods: A total of 157 participants who received lenzumestrocel and whose symptom duration was less than 2 years were included in the analysis (BM-MSC group). The survival data of placebo participants from the Pooled-Resource Open-Access ALS Clinical Trials (PROACT) database were used as the external control, and propensity score matching (PSM) was used to reduce confounding biases in baseline characteristics. Adverse events were recorded during the entire follow-up period after the first treatment. Results: Survival probability was significantly higher in the BM-MSC group compared to the external control group from the PROACT database (log-rank, p < 0.001). Multivariate Cox proportional hazard analysis showed a significantly lower hazard ratio for death in the BM-MSC group and indicated that multiple injections were more effective. Additionally, there were no serious adverse drug reactions found during the safety assessment, lasting a year after the first administration. Conclusion: The results of the present study showed that lenzumestrocel treatment had a long-term survival benefit in real-world ALS patients.

9.
Sensors (Basel) ; 23(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36772662

RESUMO

Most existing data integrity auditing protocols in cloud storage rely on proof of probabilistic data possession. Consequently, the sampling rate of data integrity verification is low to prevent expensive costs to the auditor. However, in the case of a multi-cloud environment, the amount of stored data will be huge. As a result, a higher sampling rate is needed. It will also have an increased cost for the auditor as a consequence. Therefore, this paper proposes a blockchain-based distributed data integrity verification protocol in multi-cloud environments that enables data verification using multi-verifiers. The proposed scheme aims to increase the sampling rate of data verification without increasing the costs significantly. The performance analysis shows that this protocol achieved a lower time consumption required for verification tasks using multi-verifiers than a single verifier. Furthermore, utilizing multi-verifiers also decreases each verifier's computation and communication costs.

10.
J Neurol ; 270(3): 1478-1486, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36396811

RESUMO

BACKGROUND: We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. METHODS: A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups. RESULTS: After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation. CONCLUSION: While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.


Assuntos
Miastenia Gravis , Receptores Proteína Tirosina Quinases , Humanos , Estudos Retrospectivos , Receptores Colinérgicos , Autoanticorpos , Ensaio de Imunoadsorção Enzimática
11.
Brain Commun ; 4(6): fcac299, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36458208

RESUMO

Increasing genetic evidence supports the hypothesis that variants in the annexin A11 gene (ANXA11) contribute to amyotrophic lateral sclerosis pathogenesis. Therefore, we studied the clinical aspects of sporadic amyotrophic lateral sclerosis patients carrying ANXA11 variants. We also implemented functional experiments to verify the pathogenicity of the hotspot variants associated with amyotrophic lateral sclerosis-frontotemporal dementia. Korean patients diagnosed with amyotrophic lateral sclerosis (n = 882) underwent genetic evaluations through next-generation sequencing, which identified 16 ANXA11 variants in 26 patients. We analysed their clinical features, such as the age of onset, progression rate, initial symptoms and cognitive status. To evaluate the functional significance of the ANXA11 variants in amyotrophic lateral sclerosis-frontotemporal dementia pathology, we additionally utilized patient fibroblasts carrying frontotemporal dementia-linked ANXA11 variants (p.P36R and p.D40G) to perform a series of in vitro studies, including calcium imaging, stress granule dynamics and protein translation. The frequency of the pathogenic or likely pathogenic variants of ANXA11 was 0.3% and the frequency of variants classified as variants of unknown significance was 2.6%. The patients with variants in the low-complexity domain presented unique clinical features, including late-onset, a high prevalence of amyotrophic lateral sclerosis-frontotemporal dementia, a fast initial progression rate and a high tendency for bulbar-onset compared with patients carrying variants in the C-terminal repeated annexin homology domains. In addition, functional studies using amyotrophic lateral sclerosis-frontotemporal dementia patient fibroblasts revealed that the ANXA11 variants p.P36R and p.D40G impaired intracellular calcium homeostasis, stress granule disassembly and protein translation. This study suggests that the clinical manifestations of amyotrophic lateral sclerosis and amyotrophic lateral sclerosis-frontotemporal dementia spectrum patients with ANXA11 variants could be distinctively characterized depending upon the location of the variant.

13.
Anesth Pain Med (Seoul) ; 17(4): 397-403, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36317432

RESUMO

BACKGROUND: Due to its various advantages, laparoscopic surgery is preferred over laparotomy in patients who require hepatic resection. Carbon dioxide embolism -which occurs approximately ten times more often in laparoscopic hepatectomy than in general laparoscopic surgery-presents with insignificant symptoms and may be overlooked. CASE: A 70-year-old male with hepatic cell carcinoma underwent laparoscopic hepatectomy. Though his vital signs were stable during the initiation of surgery, they became unstable during the procedure. The surgeon detected portal vein rupture, and transesophageal echocardiography was subsequently performed. A large amount of gas in the heart chamber and paradoxical embolism through a patent foramen ovale due to a right-to-left shunt were observed. We treated the symptoms, and the surgery was completed without any further issues. CONCLUSIONS: Active use of transesophageal echocardiography to identify and monitor heart functions during a suspected carbon dioxide embolism can significantly reduce morbidity and mortality associated with that embolism.

14.
J Korean Med Sci ; 37(7): e58, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35191234

RESUMO

Guillain-Barre syndrome (GBS) is an immune-mediated acute polyradiculoneuropathy and commonly occurs after a preceding infection or immunization sequalae. Following the severe acute respiratory syndrome-coronavirus-2 virus pandemic with co-introduction of massive vaccinations, several GBS cases associated with coronavirus disease 2019 (COVID-19) infection per se or after vaccination for COVID-19 were reported internationally. Herein, we report two cases of Korean GBS presenting with tetraplegia after two different COVID-19 vaccinations (42-year old man by AstraZeneca and 48-year woman by Pfizer vaccines) within four weeks after vaccination. The patients were diagnosed with clinical examination, serial electromyography, and compatible laboratory results and improved after comprehensive rehabilitative treatment and intravenous immunoglobulin therapy. Furthermore, we performed an electrodiagnostic follow-up study of each case to examine their unique characteristics.


Assuntos
Vacina BNT162/efeitos adversos , ChAdOx1 nCoV-19/efeitos adversos , Síndrome de Guillain-Barré/patologia , Quadriplegia/patologia , Vacinação/efeitos adversos , Adulto , Vacina BNT162/imunologia , COVID-19/prevenção & controle , ChAdOx1 nCoV-19/imunologia , Eletromiografia , Feminino , Síndrome de Guillain-Barré/reabilitação , Síndrome de Guillain-Barré/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Quadriplegia/reabilitação , Quadriplegia/terapia , SARS-CoV-2/imunologia
15.
Sensors (Basel) ; 21(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34300674

RESUMO

The evolution of the internet has led to the growth of smart application requirements on the go in the vehicular ad hoc network (VANET). VANET enables vehicles to communicate smartly among themselves wirelessly. Increasing usage of wireless technology induces many security vulnerabilities. Therefore, effective security and authentication mechanism is needed to prevent an intruder. However, authentication may breach user privacy such as location or identity. Cryptography-based approach aids in preserving the privacy of the user. However, the existing security models incur communication and key management overhead since they are designed considering a third-party server. To overcome the research issue, this work presents an efficient security model namely secure performance enriched channel allocation (S-PECA) by using commutative RSA. This work further presents the commutative property of the proposed security scheme. Experiments conducted to evaluate the performance of the proposed S-PECA over state-of-the-art models show significant improvement. The outcome shows that S-PECA minimizes collision and maximizes system throughput considering different radio propagation environments.

16.
Sci Rep ; 11(1): 3705, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723278

RESUMO

This study compared the characteristics and mortality of new implantation of cardiac implantable electronic device (CIED) between tertiary and non-tertiary hospitals. From national health insurance claims data in Korea, 17,655 patients, who underwent first and new implantation of CIED between 2013 and 2017, were enrolled. Patients were categorized into the tertiary hospital group (n = 11,560) and non-tertiary hospital group (n = 6095). Clinical outcomes including in-hospital death and all-cause death were compared between the two groups using propensity-score matched analysis. Patients in non-tertiary hospitals were older and had more comorbidities than those in tertiary hospitals. The study population had a mean follow-up of 2.1 ± 1.2 years. In the propensity-score matched permanent pacemaker group (n = 5076 pairs), the incidence of in-hospital death (odds ratio [OR]: 0.76, 95% confidence interval [CI]: 0.43-1.32, p = 0.33) and all-cause death (hazard ratio [HR]: 0.92, 95% CI 0.81-1.05, p = 0.24) were not significantly different between tertiary and non-tertiary hospitals. These findings were consistently observed in the propensity-score matched implantable cardioverter-defibrillator group (n = 992 pairs, OR for in-hospital death: 1.76, 95% CI 0.51-6.02, p = 0.37; HR for all-cause death: 0.95, 95% CI 0.72-1.24, p = 0.70). In patients undergoing first and new implantation of CIED in Korea, mortality was not different between tertiary and non-tertiary hospitals.


Assuntos
Desfibriladores Implantáveis/efeitos adversos , Cardiopatias/prevenção & controle , Coração/fisiopatologia , Mortalidade Hospitalar , Marca-Passo Artificial/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cardiopatias/complicações , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Sistema de Registros , República da Coreia/epidemiologia , Fatores de Risco , Centros de Atenção Terciária
17.
Entropy (Basel) ; 23(2)2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33572521

RESUMO

Cybercriminals use malicious URLs as distribution channels to propagate malware over the web. Attackers exploit vulnerabilities in browsers to install malware to have access to the victim's computer remotely. The purpose of most malware is to gain access to a network, ex-filtrate sensitive information, and secretly monitor targeted computer systems. In this paper, a data mining approach known as classification based on association (CBA) to detect malicious URLs using URL and webpage content features is presented. The CBA algorithm uses a training dataset of URLs as historical data to discover association rules to build an accurate classifier. The experimental results show that CBA gives comparable performance against benchmark classification algorithms, achieving 95.8% accuracy with low false positive and negative rates.

18.
Anesth Pain Med (Seoul) ; 15(3): 388-396, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33329841

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been an epidemic in the Republic of Korea since the first patient who came in China was confirmed as having the disease on January 19, 2020. Therefore, surgery for COVID-19-related patients is expected to increase. CASE: We experienced two cases of COVID-19-related patients who underwent surgery for femur fracture under general anesthesia. In one case, infection control to prevent transmission was achieved, while in the second case, healthcare workers were exposed to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). CONCLUSIONS: In areas where there is COVID-19 epidemic, SARS-CoV-2 real-time polymerase chain reaction should be performed before surgery in patients with symptoms of respiratory infection such as fever, cough, and sputum, or for those in whom the possibility of COVID-19 cannot be completely excluded. Efforts should be made to prevent healthcare worker's exposure and the contamination of the operating room.

19.
Nutrients ; 12(11)2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171846

RESUMO

The gut microbiota has been suggested as an important factor in the pathogenic mechanisms of amyotrophic lateral sclerosis (ALS). This study aimed to investigate whether the intake of different kinds of dietary fiber was related to the disease progression rate (∆FS) and survival time. In total, 272 Korean sporadic ALS patients diagnosed according to the revised EI Escorial criteria were recruited starting in March 2011 and were followed until the occurrence of events or the end of September 2020. The events included percutaneous endoscopic gastrostomy, tracheostomy, and death. Dietary fiber intake was calculated based on a 24-h dietary recall and classified according to five major fiber-rich foods: vegetables, fruits, grains, legumes, and nuts/seeds. Among the total participants, the group with ∆FS values lower than the mean ∆FS (0.75) was noted in the highest tertiles of total and vegetable fiber intake. Participants in the highest tertile for vegetable fiber intake showed longer survival in the Kaplan-Meier analysis (p = 0.033). Notably, vegetable fiber intake was negatively correlated with pro-inflammatory cytokine (interleukin (IL)-1ß, IL-6, and monocyte chemoattractant protein-1) levels in the cerebrospinal fluid. This study showed that vegetable fiber intake could influence the disease progression rate and survival time. Further clinical trials are needed to confirm whether dietary fiber supplementation improves the prognosis of ALS.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/epidemiologia , Fibras na Dieta , Comportamento Alimentar , Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Citocinas/líquido cefalorraquidiano , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia/epidemiologia , Verduras
20.
Sci Transl Med ; 12(566)2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087501

RESUMO

Dysregulation of calcium ion homeostasis and abnormal protein aggregation have been proposed as major pathogenic hallmarks underpinning selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS). Recently, mutations in annexin A11 (ANXA11), a gene encoding a Ca2+-dependent phospholipid-binding protein, have been identified in familial and sporadic ALS. However, the physiological and pathophysiological roles of ANXA11 remain unknown. Here, we report functions of ANXA11 related to intracellular Ca2+ homeostasis and stress granule dynamics. We analyzed the exome sequences of 500 Korean patients with sALS and identified nine ANXA11 variants in 13 patients. The amino-terminal variants p.G38R and p.D40G within the low-complexity domain of ANXA11 enhanced aggregation propensity, whereas the carboxyl-terminal ANX domain variants p.H390P and p.R456H altered Ca2+ responses. Furthermore, all four variants in ANXA11 underwent abnormal phase separation to form droplets with aggregates and led to the alteration of the biophysical properties of ANXA11. These functional defects caused by ALS-linked variants induced alterations in both intracellular Ca2+ homeostasis and stress granule disassembly. We also revealed that p.G228Lfs*29 reduced ANXA11 expression and impaired Ca2+ homeostasis, as caused by missense variants. Ca2+-dependent interaction and coaggregation between ANXA11 and ALS-causative RNA-binding proteins, FUS and hnRNPA1, were observed in motor neuron cells and brain from a patient with ALS-FUS. The expression of ALS-linked ANXA11 variants in motor neuron cells caused cytoplasmic sequestration of endogenous FUS and triggered neuronal apoptosis. Together, our findings suggest that disease-associated ANXA11 mutations can contribute to ALS pathogenesis through toxic gain-of-function mechanisms involving abnormal protein aggregation.


Assuntos
Esclerose Lateral Amiotrófica , Anexinas/genética , Esclerose Lateral Amiotrófica/genética , Cálcio , Homeostase , Humanos , Mutação/genética
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