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Breathing and urination, are vital physiological activities of the human body, continuous real-time monitoring of these physiological behaviors could offer timely feedback on an individual's health status. However, current monitoring techniques predominantly rely on cumbersome and intricate medical apparatuses, posing challenges in adapting to the diverse requirements of multi-scenario detection. Consequently, there is a growing interest in developing wearable devices capable of monitoring breathing and urination. In this work, we developed a multifunctional sensor integrating humidity and pressure sensing modes using a simple dip-coating process. By introducing sodium carboxymethyl cellulose and conductive polyaniline hybrid intercalation between MXene layers, a stable conductive network is established through hydrogen bonds and electrostatic interactions among materials. The overall electromechanical properties of the composites will be well improved. And, the effects of different conductive filler ratios and the number of dipping times on the construction of conductive networks are investigated. The multifunctional sensor exhibited improved sensing characteristics, including detecting pressures up to 532 kPa and a sensitivity of 19.58 kPa-1. Furthermore, it also demonstrates good humidity-sensing capabilities. Tests on volunteers demonstrated the potential in the detection of breathing and urination. In addition, the sensors are capable of transmitting Morse code. This interesting application will offer the possibility of normal communication for people with speech impairments. Given its utility and sustainability, the sensor has potential for applications in wearable health monitoring, intelligent life and telemedicine.
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Umidade , Ligação de Hidrogênio , Pressão , Eletricidade Estática , Dispositivos Eletrônicos Vestíveis , Humanos , Monitorização Fisiológica/instrumentação , Compostos de Anilina/química , Carboximetilcelulose Sódica/química , Propriedades de Superfície , Tamanho da PartículaRESUMO
BACKGROUND: Previous studies have observed liver abnormalities in amyotrophic lateral sclerosis (ALS) patients. This study aimed to investigate whether early signs of liver disease, measured by magnetic resonance imaging-derived iron-corrected T1-mapping (cT1), are risk factors for developing ALS. METHODS: cT1 and proton density fat fraction were measured and automatically analyzed using LiverMultiScan® software. The Fibrosis-4 index was calculated using an established formula based on age and blood markers. Cox proportional hazard models were used to examine the relationship between liver disease, liver biomarkers, and incident ALS. RESULTS: In a cohort of 533,707 individuals from UK Biobank, 24 ALS cases were identified among 28,328 participants with liver disease during the follow-up period. Among a total of 33,959 individuals with complete liver imaging data, 15 incident ALS cases were observed during a median follow-up period of 5.6 years. Individuals with liver disease had a higher risk of developing ALS, with an adjusted hazard ratio of 7.35 (95% CI 4.47-12.09; p < 0.001). An increase in cT1 was also associated with a higher risk of ALS. After adjusting for age, sex, Townsend deprivation index, smoking status, alcohol intake frequency, body mass index, proton density fat fraction, Fibrosis-4, and metabolic syndrome, an increase in cT1 remained significantly associated with a higher risk of ALS, with an adjusted hazard ratio of 3.15 (95% CI 1.79-5.55) per 1-SD increase. Sensitivity analyses confirmed these robust results. INTERPRETATION: Liver disease activity, indicated by cT1, increases the risk of developing ALS, independent of metabolic syndrome, liver fat, or fibrosis. ANN NEUROL 2024.
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BACKGROUND: Post-stroke stress can trigger instant survival but its influence on long-term ischemic stroke outcomes remains controversial. Thus, we sought to explore the associations of acute post-stroke stress evidenced by endocrine and metabolic changes, with long-term ischemic stroke outcomes. METHODS: Admissions for acute ischemic stroke within seven days of onset were prospectively recruited to determine acute endocrine and metabolic variations measured by thyroid parameters and the stress hyperglycemia ratio (SHR). Long-term ischemic stroke prognoses were followed up for one year, with the primary outcome being a modified Rankin Scale score of 3 to 6. RESULTS: A total of 887 patients were enrolled, of which 535 reached the final one-year followed up at a poor prognosis rate of 29.3%. Patients with poor outcomes were observed to have lower levels of free triiodothyronine (fT3) and higher levels of SHR on admission. Medium values (fT3, 4.4 mmol/L; SHR, 8 nmol/L) were used to divide patients into four gradient stress degrees. Larger acute endocrine and metabolic variations (fT3 < 4.4 mmol/L and SHR ≥ 8 nmol/L) were independently associated with a poor one-year prognosis (adjusted OR = 4.231, P = 0.001). CONCLUSIONS: High degrees of acute post-stroke stress may aggravate long-term ischemic stroke prognosis and timely stress-reduced interventions may help promote post-stroke living quality is equally important as survival.
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AVC Isquêmico , Humanos , Masculino , Feminino , Estudos Prospectivos , Prognóstico , Idoso , AVC Isquêmico/metabolismo , Pessoa de Meia-Idade , Tri-Iodotironina/sangue , Hiperglicemia/metabolismo , Idoso de 80 Anos ou maisRESUMO
The blood-brain barrier (BBB) is a highly selective network of various cell types that acts as a filter between the blood and the brain parenchyma. Because of this, the BBB remains a major obstacle for drug delivery to the central nervous system (CNS). In recent years, there has been a focus on developing various modifiable platforms, such as monoclonal antibodies (mAbs), nanobodies (Nbs), peptides, and nanoparticles, as both therapeutic agents and carriers for targeted drug delivery to treat brain cancers and diseases. Methods for bypassing the BBB can be invasive or noninvasive. Invasive techniques, such as transient disruption of the BBB using low pulse electrical fields and intracerebroventricular infusion, lack specificity and have numerous safety concerns. In this review, we will focus on noninvasive transport mechanisms that offer high levels of biocompatibility, personalization, specificity and are regarded as generally safer than their invasive counterparts. Modifiable platforms can be designed to noninvasively traverse the BBB through one or more of the following pathways: passive diffusion through a physio-pathologically disrupted BBB, adsorptive-mediated transcytosis, receptor-mediated transcytosis, shuttle-mediated transcytosis, and somatic gene transfer. Through understanding the noninvasive pathways, new applications, including Chimeric Antigen Receptors T-cell (CAR-T) therapy, and approaches for drug delivery across the BBB are emerging.
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BACKGROUND AND AIMS: Little is known about the ability of serological biomarkers to monitor clinical outcomes in patients with Guillain-Barré syndrome (GBS). The objective of this study was to determine the associations of liver function, easily available and convenient biomarkers, with the clinical course and outcome of severe GBS in patients. METHODS: A prospective data collection was conducted in a cohort of 343 GBS patients from multi-centers between September 2019 and December 2023. Serum samples were obtained at four-time points for mechanical ventilation (MV) patients and two-time points for non-MV patients. The primary endpoint was the need for MV during hospitalization, while secondary outcomes included the ability to walk independently and the mortality at 26-week follow-up. RESULTS: (i) A total of 208 patients were eligible, of whom 50 required MV with a median (interquartile range) ventilation duration of 15 (8-27) days. (ii) Hypohepatia, as evidenced by reduced total protein (OR 0.913 [95% CI 0.862-0.967]) and albumin (0.775 [0.679-0.884]) 1 week after treatment, along with raised liver enzymes (2.732 [1.007-7.413]), was associated with the risk of MV after adjusting for confounders. (iii) After 26-week follow-up, patients with hypohepatia were less likely to regain independent walking and exhibited higher mortality in survival analysis (all log-rank p < .05). (iv) In a cross-sectional study spanning up to 4 years of follow-up, patients with prolonged MV (≥15 days) experienced a longer time to regain independent ambulation than those with shorter MV (167 [46-316] vs. 69 [24-106], p = .036). However, no relationships between liver function and prolonged MV were revealed. INTERPRETATION: Dynamically monitoring hepatic metabolism and promptly adjusting, it can aid the improvement of GBS in patients.
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BACKGROUND: Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. METHODS: Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. RESULTS: Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (ß 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. CONCLUSIONS: Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.
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Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Progressão da Doença , Condução Nervosa , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Condução Nervosa/fisiologia , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/sangueRESUMO
To clarify the complex relationship between the factors causing safety accidents in metallurgical enterprises and predict the risk of accidents in enterprises, a correlation analysis model of the factors causing safety accidents in metallurgical enterprises based on grey Decision-Making Trial and Evaluation Laboratory/Interpretative Structural Modeling (DEMATEL/ISM) was established, and a Bayesian network early warning model was constructed on this basis. The relationship and action path of accident-causing factors in metallurgical enterprises were clarified. The factors were hierarchically divided and a multi-layer hierarchical structure model was established to obtain the neighboring cause, transitional cause, and essential cause of the accident. The results showed that the employee violation rate, the hazardous substances reserves, the toxic gas and dust pollution control compliance rate, the pass rate for equipment maintenance, and the qualification rate of special equipment were the neighboring causes of the accident. The perfection of the safety production management system was the essential cause. The Bayesian network early warning model was applied to the Fuxin Jiuxing Titanium work site. The expected risk probability of an accident was 17.9%, which was in a comparatively safe state (State2). The results obtained by the Bayesian model are consistent with those obtained by AHP and fuzzy comprehensive evaluation method, which proved the accuracy of the early warning model. The Bayesian model can give the risk probability value of the accident and the risk probability value of the accident cause factors at the same time, and include the causal relationship and conditional correlation relationship among the indicator variables in the reasoning process, which can provide targeted technical support for the construction of the emergency system of risk classification management and control.
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Background: Hearing loss (HL) is increasingly recognized as a significant global public health issue, and research on its relationship with vitamin D levels has gained wider attention. However, the association between serum biomarkers 25-hydroxyvitamin D2 (25(OH)D2) and D3 (25(OH)D3) with different types of HL remains unclear. This study aimed to investigate the potential association of serum 25(OH)D2 and 25(OH)D3 with HL in US adults. Methods: A sample of 3,684 individuals aged 20-69 years from the 2015-2016 National Health and Nutrition Examination (NHANES) was analyzed in this study. HL was defined as a pure tone average > 25 dB in either ear at low frequencies (500, 1,000, 2000 Hz), speech frequencies (500, 1,000, 2000, 4,000 Hz), and high frequencies (3,000, 4,000, 6,000, 8,000 Hz). Logistic regression was employed to examine the association between serum 25(OH)D2 and 25(OH)D3 and HL. The study population was then stratified by age, gender, race, and education level to analyze potential differences between adults in different subgroups. Results: In the multivariate analysis, it was found that serum 25(OH)D2 was independently associated with low-frequency hearing loss (LFHL) (OR: 1.012 [95% CI, 1.005-1.020]) and speech-frequency hearing loss (SFHL) (OR: 1.011 [95% CI, 1.003-1.018]). Restrictive cubic spline analysis demonstrated a linear dose-response relationship between serum 25(OH)D2 levels and LFHL (p for linearity <0.001), as well as SFHL (p for linearity = 0.001). Conversely, an L-shaped association was observed between serum 25(OH)D3 levels and both LFHL (p for nonlinearity = 0.014) and SFHL (p for nonlinearity = 0.025), with threshold values identified at 35.3 and 36.5 nmol/L, respectively. Higher levels of serum 25(OH)D3 were associated with a lower probability of high-frequency hearing loss (HFHL) (OR: 0.994 [95% CI, 0.989-0.999]), with a threshold value identified at 53.9 nmol/L. Furthermore, a significant interaction between diabetes and serum 25(OH)D2 in LFHL was revealed through subgroup analysis (p = 0.041). In the non-diabetic population, serum 25(OH)D2 maintained its association with LFHL. Conclusion: Our findings suggested a positive association between serum 25(OH)D2 concentrations and both LFHL and SFHL in the studied cohort. Additionally, an L-shaped relationship was found between serum 25(OH)D3 and LFHL and SFHL, and higher levels of serum 25(OH)D3 were identified to be associated with a lower risk of HFHL.
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In recent years, flexible and stretchable strain sensors have emerged as a prominent area of research, primarily due to their remarkable stretchability and extremely low strain detection threshold. Nevertheless, the advancement of sensors is currently constrained by issues such as complexity, high costs, and limited durability. To tackle the aforementioned issues, this study introduces a lepidophyte-inspired flexible, stretchable strain sensor (LIFSSS). The stretchable bioelectronics composites were composed of multiwalled carbon nanotubes, graphene, neodymium iron boron, and polydimethylsiloxane. Unique biolepidophyted microstructures and magnetic conductive nanocomposites interact with each other through synergistic interactions, resulting in the effective detection of tensile strain and magnetic excitation. The LIFSSS exhibits a 170% tensile range, a linearity of 0.99 in 50-170% strain (0.96 for full-scale range), and a fine durability of 7000 cycles at 110% tensile range. The sensor accurately detects variations in linear tensile force, human movement, and microexpressions. Moreover, LIFSSS demonstrates enhanced efficacy in sign language recognition for individuals with hearing impairments and magnetic grasping for robotic manipulators. Hence, the LIFSSS proposed in this study shows potential applications in various fields, including bioelectronics, electronic skin, and physiological activity monitoring.
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Dimetilpolisiloxanos , Grafite , Nanocompostos , Nanotubos de Carbono , Dispositivos Eletrônicos Vestíveis , Nanocompostos/química , Nanotubos de Carbono/química , Humanos , Dimetilpolisiloxanos/química , Grafite/química , Neodímio/química , Resistência à Tração , Técnicas Biossensoriais/métodos , Fenômenos BiomecânicosRESUMO
The utilization of anti-CD3/CD28 magnetic beads for T cell expansion in vitro has been investigated for adoptive cell transfer therapy. However, the impact of the CD3/CD28 antibody ratio on T cell differentiation and function remains incompletely elucidated. This study seeks to address this knowledge gap. To begin with, CD3 antibodies with a relatively low avidity for Jurkat cells (Kd = 13.55 nM) and CD28 antibodies with a relatively high avidity (Kd = 5.79 nM) were prepared. Afterwards, anti-CD3/CD28 antibodies with different mass ratios were attached to magnetic beads to examine the impacts of different antibody ratios on T cell capture, and proliferation. The research demonstrated that the most significant expansion of T cells was stimulated by the anti-CD3/CD28 magnetic beads with a mass ratio of 2:1 for CD3 antibodies and CD28 antibodies. Moreover, CD25 and PD1 expression of expanded T cells increased and then decreased, with lower CD25 and PD1 expression in the later stages of expansion indicating that T cells were not depleted. These T cells, which are massively expanded in vitro and have excellent expansion potential, can be infused back into the patient to treat tumor patients. This study shows that altering the ratio of anti-CD3/CD28 antibodies can control the strength of T cell stimulation, thereby leading to the improvement of T cell activation. This discovery can be utilized as a guide for the creation of other T cell stimulation approaches, which is beneficial for the further development of tumor immunotherapy technology.
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To effectively control the dust generated by coal mining operations, a new type of cyclonic pneumatic mist curtain dust control device was developed. Using CFD software, numerical simulations were conducted on the internal airflow velocity field, the exit velocity of the cyclonic pneumatic mist curtain, and the mist droplet particle field of the curtain. Experiments were carried out to measure the spray coverage, droplet size, and the dust control performance of the model device. The results indicate that when the water pump supply pressure is 8 MPa, the fan supply wind speed is 12 m/s, and the nozzle installation angle is 75 degrees, the cyclonic pneumatic mist curtain dust control device model operates under optimal conditions. The effective coverage of the cyclonic mist curtain is 380 × 3300 mm, fully suppressing dust generation on one side of the curtain. An optimal dust removal distance of about 90 cm was determined. After installing the cyclonic pneumatic mist curtain dust control device, the average dust reduction efficiency for respirable dust reached 91.07%, and the overall dust reduction efficiency achieved 93.34%.
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When purifying mAb from serum-containing hybridoma culture supernatant, it is essential that mouse IgG remains free from contaminations of bovine IgG. However, the broadly used Protein A resin cannot achieve this goal due to binding between both mouse and bovine IgG. Here, a novel nanobody-based affinity purification magnetic beads that discriminates mouse IgG from bovine IgG was developed. To bind all subtypes of mouse IgG (IgG1, IgG2a, IgG2b and IgG3) that contain the kappa light chain, mCK (mouse kappa constant region)-specific nanobody binders were selected from an immune phage display VHH library; this library was constructed with peripheral blood mononuclear cells (PBMCs), which were collected from Bactrian camels immunized with a mix of intact mouse IgGs (IgG1, IgG2a, IgG2b and IgG3). A novel clone that exhibited a higher expression level and a higher binding affinity was selected (4E6). Then, the 4E6 nanobody in the format of VHH-hFC (human Fc) was conjugated on magnetic beads with a maximal binding capacity of 15.41±0.69 mg mouse IgG/mL beads. Furthermore, no bovine IgG could be copurified from hybridoma culture supernatant with immunomagnetic beads. This approach is valuable for the large-scale in vitro production of highly pure antibodies by hybridoma cells.
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Anticorpos Monoclonais , Animais , Bovinos , Humanos , Camundongos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Camelus , Cromatografia de Afinidade/métodos , Hibridomas , Regiões Constantes de Imunoglobulina/química , Imunoglobulina G/isolamento & purificação , Imunoglobulina G/imunologia , Cadeias kappa de Imunoglobulina/imunologia , Cadeias kappa de Imunoglobulina/química , Biblioteca de Peptídeos , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/isolamento & purificaçãoRESUMO
BACKGROUND: Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in understanding the complex etiology of DPN, there are no approved therapies that can halt the development of DPN, or target the damaged nerve. Therefore, clarifying the pathogenesis of DPN and finding effective treatment are the crucial issues for the clinical management of DPN. AIMS: This review is aiming to summary the current knowledge on the pathogenesis of DPN, especially the mechanism and application of inflammatory response. METHODS: We systematically summarized the latest studies on the pathogenesis and therapeutic strategies of diabetic neuropathy in PubMed. RESULTS: In this seminal review, the underappreciated role of immune activation in the progression of DPN is scrutinized. Novel insights into the inflammatory regulatory mechanisms of DPN have been unearthed, illuminating potential therapeutic strategies of notable clinical significance. Additionally, a nuanced examination of DPN's complex etiology, including aberrations in glycemic control and insulin signaling pathways, is presented. Crucially, an emphasis has been placed on translating these novel understandings into tangible clinical interventions to ameliorate patient outcomes. CONCLUSIONS: This review is distinguished by synthesizing cutting-edge mechanisms linking inflammation to DPN and identifying innovative, inflammation-targeted therapeutic approaches.
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Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Neuropatias Diabéticas/terapia , Insulina , Inflamação/complicações , Resultado do Tratamento , Transdução de SinaisRESUMO
Because adenomyosis (AM) ectopic primary cells are hard to come by, have a short lifespan, and the characteristics that alter over time, their utility in AM research is constrained. This study aimed to establish a line of immortalized human adenomyosis ectopic cell (ihAMEC) to change this situation. Primary cells were obtained from AM ectopic lesion tissue and then infected with Simian Vacuolating Virus 40 Tag (SV40 T) lentivirus and screened to establish immortalized cells. We verified the main features and found that the ihAMEC could be cultured for more than 50 generations and the proliferation ability of ihAMEC was more active than that of primary cells. The cytoskeleton and cell types of ihAMEC were similar to primary cells and maintained a normal karyotype. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins, and estrogen/progesterone receptors in ihAMEC was similar to the expression seen in primary cells. In addition, the response of ihAMEC under estrogen treatment and Lipopolysaccharide intervention is similar to primary cells. The clonogenic ability of ihAMEC was lower than tumor cells and did not form tumors in tumorigenicity assays. Thus, ihAMEC can be used as in vitro cellular model for pathogenesis and drug development studies regarding AM.
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Adenomiose , Feminino , Humanos , Endométrio/patologia , Linhagem Celular , Transição Epitelial-Mesenquimal , Estrogênios , Proliferação de CélulasRESUMO
The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has resulted in devastating medical and economic consequences worldwide over the past 3 years. As the pandemic enters a new stage, it is essential to consider the potential impact on rare diseases such as Guillain-Barre syndrome (GBS), which has been intimately associated with COVID-19 since the first COVID-19-related GBS case was reported in January 2020. There are notable differences between COVID-19-related GBS and GBS without COVID-19 in terms of diagnostic types and clinical manifestations. Furthermore, with the widespread administration of COVID-19 vaccines, there have been reports of GBS occurring shortly after vaccination, which requires close attention despite its rarity. This review also explores the vaccines associated with heightened GBS risks, offering insights that may guide vaccination policies and clinical practice. To provide a visual summary of these findings, we have included a graphical abstract. This article will discuss the characteristic manifestations of GBS patients after being positive for the novel coronavirus and the safety of several COVID-19 vaccines. Firstly, this article comprehensively expounds and discusses the epidemiological aspects of novel coronavirus-related GBS. For example, from the perspective of the same population, the expected incidence of GBS in the COVID-19-positive population (persons/100,000 persons/ year) is about 43 times that of the COVID-19-negative population, and the incidence of GBS is significantly increased. Secondly, the clinical characteristics of COVID-19-negative GBS patients and SARS-CoV-2-GBS (SC2-GBS) patients were summarized and compared. Thirdly, this article reviews GBS cases in the current adverse events after COVID-19 vaccination and analyzes and discusses from multiple perspectives, such as the incidence of GBS events, the age proportion of patients, and the interval of onset.
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Diabetic peripheral neuropathy (DPN) is a pervasive and incapacitating sequela of diabetes, affecting a significant proportion of those diagnosed with the disease, yet an effective treatment remains elusive. Vitamins have been extensively studied, emerging as a promising target for diagnosing and treating various systemic diseases, but their role in DPN is not known. This review collates and synthesizes knowledge regarding the interplay between vitamins and DPN, drawing on bibliographies from prior studies and relevant articles, and stratifying the therapeutic strategies from prophylactic to interventional. In addition, the clinical evidence supporting the use of vitamins to ameliorate DPN is also evaluated, underscoring the potential of vitamins as putative therapeutic agents. We anticipate that this review will offer novel insights for developing and applying vitamin-based therapies for DPN.
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Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Humanos , Vitaminas/farmacologia , Vitaminas/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Vitamina A , Vitamina KRESUMO
Hydrogen sulfide (H2S) is the third gas signaling molecule that has been shown to be involved in the regulating vital activities in the body, including inhibition of aging. However, it is unknown whether H2S alleviates aging in the kidney and glomerular mesangial cells (GMCs) by modulating their mitophagy. Here, results of experiments in vivo and in vitro showed that compared with control group, the renal function of mice and GMCs viability were decreased in D-gal (D-galactose) group, while the activity of SA-ß-gal and p21 expression were increased, Cyclin D1 and Klotho expressions were decreased; H2S content and CSE expression were lower; ROS and MDA contents and mitochondrial permeability transition pore (mPTP) opening were risedose; ATP production and mitochondrial membrane potential (Δψm) were reduced; Apoptotic rate, the expression of Cleaved caspase-9 and -3, Cyt c, p62 and Drp1 were enhanced and the expression of Bcl-2, Mfn2, Beclin-1, LC3 II/I, PINK1 and parkin were decreased. In addition, phospho-AMPK/AMPK and phospho-ULK1/ULK1 were also decreased significantly. Compared with the D-gal group, the changes of above indexes were reversed in the D-gal + NaHS (Sodium hydrosulfide, an exogenous H2S donor) group. The reverse effects of NaHS were similar to that of AICAR (an AMPK agonist) and kinetin (a PINK1 agonist), respectively. Taken together, these results suggest that exogenous H2S increases mitophagy and inhibits apoptosis as well as oxidative stress through up-regulation of AMPK-ULK1-PINK1-parkin pathway, which delays kidney senescence in mice.
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Células Mesangiais , Mitofagia , Proteínas Quinases Ativadas por AMP , Rim , Estresse OxidativoRESUMO
AIMS: Increasing numbers of reports link vitamin D deficiency to diabetic peripheral neuropathy (DPN), yet evidence regarding neurological deficits and electromyogram is scarce. The present multi-centre study sought to investigate these associations based on objective quantifications. MATERIALS AND METHODS: Information on DPN-related symptoms, signs, all diabetic microvascular complications, and nerve conduction abilities (quantified by nerve conduction amplitude and velocity, F-wave minimum latency (FML) of peripheral nerves) were collected from a derivation cohort of 1192 patients with type 2 diabetes (T2D). Correlation, regression analysis, and restricted cubic splines (RCS) were used to explore linear and non-linear relationships between vitamin D and DPN, which were validated in an external cohort of 223 patients. RESULTS: Patients with DPN showed lower levels of vitamin D than those without DPN; patients with vitamin D deficiency (<30 nmol/L) tended to suffer more DPN-related neurological deficits (paraesthesia, prickling, abnormal temperature, ankle hyporeflexia, and distal pall hypoesthesia correlating with MNSI-exam score (Y = -0.005306X + 2.105, P = 0.048). Worse nerve conduction abilities (decreased motor nerve amplitude, sensory nerve amplitude, motor nerve velocity, and increased FML) were also observed in these patients. Vitamin D had a significant threshold association with DPN (adjusted OR = 4.136, P = 0.003; RCS P for non-linearity = 0.003) and correlates with other microvascular complications (diabetic retinopathy and diabetic nephropathy). CONCLUSIONS: Vitamin D is associated with the conduction ability of peripheral nerves and may have a nerve- and threshold-selective relationship with the prevalence and severity of DPN among patients with T2D.
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Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Deficiência de Vitamina D , Humanos , Diabetes Mellitus Tipo 2/complicações , Vitamina D , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/complicações , População do Leste Asiático , Fluormetolona , Estudos de Condução Nervosa , Condução Nervosa/fisiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologiaRESUMO
Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus with a high incidence. Oxidative stress, which is a crucial pathophysiological pathway of DPN, has attracted much attention. The distortion in the redox balance due to the overproduction of reactive oxygen species (ROS) and the deregulation of antioxidant defense systems promotes oxidative damage in DPN. Therefore, we have focused on the role of oxidative stress in the pathogenesis of DPN and elucidated its interaction with other physiological pathways, such as the glycolytic pathway, polyol pathway, advanced glycosylation end products, protein kinase C pathway, inflammation, and non-coding RNAs. These interactions provide novel therapeutic options targeting oxidative stress for DPN. Furthermore, our review addresses the latest therapeutic strategies targeting oxidative stress for the rehabilitation of DPN. Antioxidant supplements and exercise have been proposed as fundamental therapeutic strategies for diabetic patients through ROS-mediated mechanisms. In addition, several novel drug delivery systems can improve the bioavailability of antioxidants and the efficacy of DPN.
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Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Neuropatias Diabéticas/tratamento farmacológico , Estresse Oxidativo/fisiologia , Produtos Finais de Glicação Avançada/metabolismoRESUMO
The common mycotoxins in polluted grains are aflatoxin B1(AFB1), zearalenone (ZEN) and deoxynivalenol (DON). Because of the potential threat to humans and animals, it is necessary to detect mycotoxin contaminants rapidly. At present, later flow immunoassay (LFIA) is one of the most frequently used methods for rapid analysis. However, multistep sample pretreatment processes and organic solvents are also required to extract mycotoxins from grains. In this study, we developed a one-step and "green" sample pretreatment method without using organic solvents. By combining with LFIA test strips and a handheld detection device, an on-site method for the rapid detection of AFB1, ZEN and DON was developed. The LODs for AFB1, ZEN and DON in corn are 0.90 µg/kg, 7.11 µg/kg and 10.6 µg/kg, respectively, and the working ranges are from 1.25 µg/kg to 40 µg/kg, 20 µg/kg to 2000 µg/kg and 35 µg/kg to 1500 µg/kg, respectively. This method has been successfully applied to the detection of AFB1, ZEN and DON in corn, rice and peanut, with recoveries of 89 ± 3%-106 ± 3%, 86 ± 2%-108 ± 7% and 90 ± 2%-106 ± 10%, respectively. The detection results for the AFB1, ZEN and DON residues in certified reference materials by this method were in good agreement with their certificate values.