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Pancreatic ductal adenocarcinoma (PDAC) suffers from a lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for the discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating the analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, the throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from the early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In the discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including a short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.
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Many animals rely on an internal heading representation when navigating in varied environments1-10. How this representation is linked to the sensory cues that define different surroundings is unclear. In the fly brain, heading is represented by 'compass' neurons that innervate a ring-shaped structure known as the ellipsoid body3,11,12. Each compass neuron receives inputs from 'ring' neurons that are selective for particular visual features13-16; this combination provides an ideal substrate for the extraction of directional information from a visual scene. Here we combine two-photon calcium imaging and optogenetics in tethered flying flies with circuit modelling, and show how the correlated activity of compass and visual neurons drives plasticity17-22, which flexibly transforms two-dimensional visual cues into a stable heading representation. We also describe how this plasticity enables the fly to convert a partial heading representation, established from orienting within part of a novel setting, into a complete heading representation. Our results provide mechanistic insight into the memory-related computations that are essential for flexible navigation in varied surroundings.
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Percepção Visual , Animais , Cálcio/fisiologia , Drosophila melanogaster , Cabeça , Plasticidade Neuronal , Neurônios/fisiologia , Optogenética , Orientação EspacialRESUMO
Although several methods are being applied to treat peripheral nerve injury, a perfect treatment that leads to full functional recovery has not yet been developed. SMAD (Suppressor of Mothers Against Decapentaplegic Homolog) plays a crucial role in nerve regeneration by facilitating the survival and growth of nerve cells following peripheral nerve injury. We conducted a systematic literature review on the role of SMAD in this context. Following peripheral nerve injury, there was an increase in the expression of SMAD1, -2, -4, -5, and -8, while SMAD5, -6, and -7 showed no significant changes; SMAD8 expression was decreased. Specifically, SMAD1 and SMAD4 were found to promote nerve regeneration, whereas SMAD2 and SMAD6 inhibited it. SMAD exerts its effects by promoting neuronal survival and growth through BMP/SMAD1, BMP/SMAD4, and BMP/SMAD7 signaling pathways. Furthermore, it activates nerve regeneration programs via the PI3K/GSK3/SMAD1 pathway, facilitating active regeneration of nerve cells and subsequent functional recovery after peripheral nerve damage. By leveraging these mechanisms of SMAD, novel strategies for treating peripheral nerve damage could potentially be developed. We aim to further elucidate the precise mechanisms of nerve regeneration mediated by SMAD and explore the potential for developing targeted nerve treatments based on these findings.
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Praziquantel (PZQ) is currently the only approved drug for treating clonorchiasis, but its poor efficacy against Clonorchis sinensis larvae has highlighted the need to develop newer drugs. In this study, to address this challenge, we investigated the anti-parasitic efficacy of miltefosine (MLT), curcumin (CUR), and PZQ against C. sinensis metacercariae (CsMC), newly excysted juvenile worms (CsNEJs), and adults. Larvicidal effects of MLT and CUR surpassed those elicited by PZQ in vitro. These two drugs exerted their effect against both CsMC and CsNEJs in a dose- and time-dependent manner. To confirm the effect of these drugs in vivo, Syrian golden hamsters were orally infected with 100 CsMC and subsequently treated with MLT, CUR, or PZQ at 1 and 4 weeks post-infection (wpi). MLT and CUR reduced the worm recoveries at 1 and 4 wpi, indicating that these drugs were efficacious against both larvae and adult C. sinensis. PZQ was only efficacious against adult worms. Interestingly, both MLT and CUR showed lower levels of C. sinensis-specific IgG responses than the infection control group, implying that worm burden and bile IgG responses could be correlated. These results indicate that MLT and CUR are efficacious against both larval and adult stages of C. sinensis, thereby highlighting their potential for further development as alternative therapeutic options for clonorchiasis.
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Anti-Helmínticos , Clonorquíase , Clonorchis sinensis , Curcumina , Fosforilcolina , Praziquantel , Animais , Clonorchis sinensis/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/uso terapêutico , Clonorquíase/tratamento farmacológico , Clonorquíase/parasitologia , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Fosforilcolina/farmacologia , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/farmacologia , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Mesocricetus , Larva/efeitos dos fármacos , Cricetinae , Masculino , Metacercárias/efeitos dos fármacosRESUMO
Height is known to be a classically heritable trait controlled by complex polygenic factors. Numerous height-associated genetic variants across the genome have been identified so far. It is also a representative of externally visible characteristics (EVC) for predicting appearance in forensic science. When biological evidence at a crime scene is deficient in identifying an individual, the examination of forensic DNA phenotyping using some genetic variants could be considered. In this study, we aimed to predict 'height', a representative forensic phenotype, by using a small number of genetic variants when short tandem repeat (STR) analysis is hard with insufficient biological samples. Our results not only replicated previous genetic signals but also indicated an upward trend in polygenic score (PGS) with increasing height in the validation and replication stages for both genders. These results demonstrate that the established SNP sets in this study could be used for height estimation in the Korean population. Specifically, since the PGS model constructed in this study targets only a small number of SNPs, it contributes to enabling forensic DNA phenotyping even at crime scenes with a minimal amount of biological evidence. To the best of our knowledge, this was the first study to evaluate a PGS model for height estimation in the Korean population using GWAS signals. Our study offers insight into the polygenic effect of height in East Asians, incorporating genetic variants from non-Asian populations.
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Povo Asiático , Estatura , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Herança Multifatorial/genética , Feminino , Estatura/genética , República da Coreia , Povo Asiático/genética , Genética Forense/métodos , Adulto , Estudo de Associação Genômica Ampla/métodos , Fenótipo , Repetições de Microssatélites/genética , Pessoa de Meia-IdadeRESUMO
PURPOSE: To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. DESIGN: Nationwide population-based cohort study. PARTICIPANTS: From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. METHODS: The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. MAIN OUTCOME MEASURES: Cumulative incidence and risks of incidence of RAO and RVO from the index date to day 60. RESULTS: In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P = 0.021). CONCLUSIONS: Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Vacinas contra COVID-19 , COVID-19 , Oclusão da Artéria Retiniana , Oclusão da Veia Retiniana , Feminino , Humanos , Masculino , Vacina de mRNA-1273 contra 2019-nCoV , Estudos de Coortes , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , Teste para COVID-19 , Vacinas contra COVID-19/efeitos adversos , Artéria Retiniana , Oclusão da Artéria Retiniana/etiologia , Oclusão da Artéria Retiniana/complicações , Oclusão da Veia Retiniana/epidemiologia , Oclusão da Veia Retiniana/etiologia , Oclusão da Veia Retiniana/diagnóstico , Vacinação/efeitos adversosRESUMO
Pacing induced cardiomyopathy (PICM) can occur as a complication due to pacing the right ventricle. Its precise definition varies across different studies, leading to uncertainty as to the best approach for managing this entity. More than 10% of patients who undergo chronic right ventricular pacing develop PICM. Risk factors associated with PICM include reduced left ventricular ejection fraction (LVEF), the proportion of right ventricular pacing, and paced QRS duration. The main approach to treating PICM has been upgrading to biventricular pacing cardiac resynchronization therapy when the LVEF decreases. However, emerging evidence suggest that conduction system pacing might provide an opportunity to manage PICM.
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PURPOSE: This retrospective case series aimed to assess the concordance between clinical diagnoses of punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP) using the 2021 Standardization of Uveitis Nomenclature (SUN) Working Group criteria. METHODS: Using the medical records of the patients, we reevaluated 100 eyes of 75 patients with idiopathic multifocal chorioretinal inflammatory lesions based on SUN criteria and compared the result to the clinical diagnosis. RESULTS: Of 100 eyes, 29 eyes (29%) were diagnosed as PIC and 15 eyes (15%) were diagnosed as MCP using SUN criteria, and 56 (56%) eyes could not be diagnosed as either. Clinically diagnosed PIC eyes were significantly more myopic than the clinically diagnosed MCP eyes (mean spherical equivalent -6.65 ± 4.63 vs. -3.85 ± 2.31, P = 0.01). Sixteen eyes with vitreous inflammation were all clinically diagnosed as MCP, but four (25%) could not be diagnosed as MCP using SUN criteria. CONCLUSIONS: The existing diagnostic criteria showed limitations in capturing all clinical cases of PIC or MCP, and adding or revising criteria on features such as vitreous inflammation or myopia, could be considered to enhance diagnostic accuracy.
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Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and affects millions of individuals globally. AD is associated with cognitive decline and memory loss that worsens with aging. A statistical report using U.S. data on AD estimates that approximately 6.9 million individuals suffer from AD, a number projected to surge to 13.8 million by 2060. Thus, there is a critical imperative to pinpoint and address AD and its hallmark tau protein aggregation early to prevent and manage its debilitating effects. Amyloid-ß and tau proteins are primarily associated with the formation of plaques and neurofibril tangles in the brain. Current research efforts focus on degrading amyloid-ß and tau or inhibiting their synthesis, particularly targeting APP processing and tau hyperphosphorylation, aiming to develop effective clinical interventions. However, navigating this intricate landscape requires ongoing studies and clinical trials to develop treatments that truly make a difference. Genome-wide association studies (GWASs) across various cohorts identified 40 loci and over 300 genes associated with AD. Despite this wealth of genetic data, much remains to be understood about the functions of these genes and their role in the disease process, prompting continued investigation. By delving deeper into these genetic associations, novel targets such as kinases, proteases, cytokines, and degradation pathways, offer new directions for drug discovery and therapeutic intervention in AD. This review delves into the intricate biological pathways disrupted in AD and identifies how genetic variations within these pathways could serve as potential targets for drug discovery and treatment strategies. Through a comprehensive understanding of the molecular underpinnings of AD, researchers aim to pave the way for more effective therapies that can alleviate the burden of this devastating disease.
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Doença de Alzheimer , Proteínas tau , Doença de Alzheimer/metabolismo , Doença de Alzheimer/etiologia , Humanos , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Estudo de Associação Genômica Ampla , ProteóliseRESUMO
Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration.
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Chaperonina 60 , Mitocôndrias , Estresse Oxidativo , Chaperonina 60/metabolismo , Chaperonina 60/genética , Humanos , Animais , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Apoptose , Doenças Neurodegenerativas/metabolismo , Dobramento de Proteína , Espécies Reativas de Oxigênio/metabolismoRESUMO
The heat shock response is an evolutionarily conserved mechanism that protects cells or organisms from the harmful effects of various stressors such as heat, chemicals toxins, UV radiation, and oxidizing agents. The heat shock response triggers the expression of a specific set of genes and proteins known as heat shock genes/proteins or molecular chaperones, including HSP100, HSP90, HSP70, HSP60, and small HSPs. Heat shock proteins (HSPs) play a crucial role in thermotolerance and aiding in protecting cells from harmful insults of stressors. HSPs are involved in essential cellular functions such as protein folding, eliminating misfolded proteins, apoptosis, and modulating cell signaling. The stress response to various environmental insults has been extensively studied in organisms from prokaryotes to higher organisms. The responses of organisms to various environmental stressors rely on the intensity and threshold of the stress stimuli, which vary among organisms and cellular contexts. Studies on heat shock proteins have primarily focused on HSP70, HSP90, HSP60, small HSPs, and ubiquitin, along with their applications in human biology. The current review highlighted a comprehensive mechanism of heat shock response and explores the function of heat shock proteins in stress management, as well as their potential as therapeutic agents and diagnostic markers for various diseases.
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Proteínas de Choque Térmico , Resposta ao Choque Térmico , Humanos , Proteínas de Choque Térmico/metabolismo , AnimaisRESUMO
BACKGROUND: Currently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, in which 10% 10-year CVD risk indicates clinical intervention. However, this benchmark has limited efficacy in clinical practice and the need for a more simple, non-invasive risk stratification tool is necessary. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aims to further validate our biomarker, Reti-CVD, (1) to detect risk group of ≥ 10% in 10-year CVD risk and (2) enhance risk assessment in individuals with QRISK3 of 7.5-10% (termed as borderline-QRISK3 group) using the UK Biobank. METHODS: Reti-CVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of Reti-CVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding Reti-CVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups. RESULTS: Among 48,260 participants with no history of CVD, 6.3% had CVD events during the 11-year follow-up. Reti-CVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.41; 95% confidence interval [CI], 1.30-1.52) with a 13.1% (95% CI, 11.7-14.6%) 10-year CVD risk in Reti-CVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in Reti-CVD-high-risk group (11.5% in non-statin cohort [n = 45,473], 11.5% in stage 1 hypertension cohort [n = 11,966], and 14.2% in middle-aged cohort [n = 38,941]). C statistics increased by 0.014 (0.010-0.017) in non-statin cohort, 0.013 (0.007-0.019) in stage 1 hypertension cohort, and 0.023 (0.018-0.029) in middle-aged cohort for CVD event prediction after adding Reti-CVD to QRISK3. CONCLUSIONS: Reti-CVD has the potential to identify individuals with ≥ 10% 10-year CVD risk who are likely to benefit from earlier preventative CVD interventions. For borderline-QRISK3 individuals with 10-year CVD risk between 7.5 and 10%, Reti-CVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in adult groups that may be pre-disposed to CVD.
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Doenças Cardiovasculares , Aprendizado Profundo , Hipertensão , Adulto , Pessoa de Meia-Idade , Humanos , Doenças Cardiovasculares/epidemiologia , Bancos de Espécimes Biológicos , Fatores de Risco , Reino Unido/epidemiologia , Hipertensão/complicações , BiomarcadoresRESUMO
BACKGROUND: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. RESULTS: The overall survival time was 769 days (range 14-2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126-2163 days), mycophenolate mofetil 865 days (range 39-2191 days), cyclosporin 441 days (range 11-2176 days), cytosine arabinoside 754 days (range 6-1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23-1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. CONCLUSIONS: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.
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Doenças do Cão , Encefalomielite , Meningoencefalite , Humanos , Cães , Animais , Imunossupressores/efeitos adversos , Estudos Retrospectivos , Ácido Micofenólico/efeitos adversos , Leflunomida/uso terapêutico , Prognóstico , Meningoencefalite/tratamento farmacológico , Meningoencefalite/veterinária , Citarabina/efeitos adversos , Encefalomielite/veterinária , Doenças do Cão/diagnósticoRESUMO
PURPOSE: Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare degenerative disease that affects the peripheral retina. Reports of PEHCR in Asian patients are rare. Thus, the aim of this study was to investigate the clinical characteristics and outcomes of PEHCR in Asian patients. METHODS: A retrospective chart review of 33 eyes of 29 Asian patients with PEHCR. RESULTS: The mean age of the patients was 70 years, and 75.9% of them were women. Vitreous hemorrhage occurred in 51.5% of eyes during a mean follow-up of 43.1 months. The occurrence of vitreous hemorrhage was associated with a thicker baseline subfoveal choroid ( P = 0.001) and the male sex ( P = 0.005). Final visual acuity was less than 20/200 in 29.2% of eyes. The predictive factors for a final visual acuity worse than 20/200 included poor initial visual acuity ( P = 0.002), initial lesion involvement of more than 180° of the peripheral retina ( P = 0.03), an extension of subretinal hemorrhage to the macula ( P = 0.040), and absence of complete tumor regression ( P = 0.02). CONCLUSION: Asian PEHCR patients seem to be more frequently associated with vitreous hemorrhages, especially in male patients with thicker choroids. Although PEHCR was largely self-limiting, approximately one-third of the eyes ended up with a visual acuity of less than 20/200 with extensive lesion involvement.
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Doenças da Coroide , Doenças Retinianas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Asiático , Coriorretinite , Doenças da Coroide/epidemiologia , Retina , Doenças Retinianas/epidemiologia , Hemorragia Retiniana , Estudos Retrospectivos , Hemorragia Vítrea/complicações , Resultado do TratamentoRESUMO
PURPOSE: To investigate bilateral macular features on optical coherence tomography in patients with unilateral peripheral exudative hemorrhagic chorioretinopathy (PEHCR). METHODS: In this cross-sectional study, optical coherence tomography features of affected eyes (PEHCR group, n = 30) and unaffected contralateral eyes (contralateral group, n = 30) were investigated. Age-matched and sex-matched patients with polypoidal choroidal vasculopathy (PCV group, n = 51) and healthy controls (normal group, n = 50) were included to compare choroidal thickness, measured at six points apart from the fovea, with the PEHCR group. RESULTS: Subretinal drusenoid deposits were the most common feature in the PEHCR (20%) and contralateral (23%) groups, followed by soft drusen. Although the macular choroid was comparably thin in both the PEHCR and contralateral groups, pachyvessels were also observed. The choroids of the PEHCR group were significantly thinner than those of the normal group at the subfovea and 1-mm temporal to the fovea and considerably thinner than those of the polypoidal choroidal vasculopathy group from 3-mm nasal to 3-mm temporal to the fovea. CONCLUSION: In patients with unilateral PEHCR, bilateral choroidal thinning and drusenoid deposit accumulation were noted in the macula. The pathophysiology of PEHCR may be a rare peripheral complication of age-related macular degeneration with pathologic choroid.
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Doenças da Coroide , Drusas Retinianas , Humanos , Estudos Transversais , Angiofluoresceinografia , Doenças da Coroide/diagnóstico , Doenças da Coroide/patologia , Corioide/patologia , Drusas Retinianas/diagnóstico , Drusas Retinianas/etiologia , Drusas Retinianas/patologia , Tomografia de Coerência Óptica , Estudos RetrospectivosRESUMO
Facial nerve palsy directly impacts the quality of life, with patients with facial nerve palsy showing increased rates of depression and limitations in social activities. Although facial nerve palsy is not life-threatening, it can devastate the emotional and social lives of affected individuals. Hence, improving the prognosis of patients with this condition is of vital importance. The prognosis of patients with facial nerve palsy is determined by the cause of the disease, the degree of damage, and the treatment provided. The facial nerve can be easily damaged by middle ear and temporal bone surgery, trauma or infection, and tumors of the peripheral facial nerve or tumors surrounding the nerve secondary to systemic disease. In addition, idiopathic, acquired immunodeficiency syndrome and autoimmune diseases may damage the facial nerve. The treatment used for facial paralysis depends on the cause. Treatment of facial nerve amputation injury varies depending on the degree of facial nerve damage, comorbidities, and duration of injury. Recently, interest has increased in Toll-like receptors (TLRs) related to innate immune responses, as these receptors are known to be related to nerve regeneration. In addition to innate immune cells, both neurons and glia of the central nervous system (CNS) and peripheral nervous system (PNS) express TLRs. A comprehensive literature review was conducted to assess the expression and role of TLRs in peripheral nerve injury and subsequent regeneration. Studies conducted on rats and mice have demonstrated the expression of TLR1-13. Among these, TLR2-5 and TLR7 have received the most research attention in relation to facial nerve degeneration and regeneration. TLR10, TLR11, and TLR13 increase during compression injury of the facial nerve, whereas during cutting injury, TLR1-5, TLR8, and TLR10-13 increase, indicating that these TLRs are involved in the degeneration and regeneration of the facial nerve following each type of injury. Inadequate TLR expression or absence of TLR responses can hinder regeneration after facial nerve damage. Animal studies suggest that TLRs play an important role in facial nerve degeneration and regeneration.
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Traumatismos do Nervo Facial , Camundongos , Ratos , Animais , Receptor 1 Toll-Like , Nervo Facial , Qualidade de Vida , Receptores Toll-Like , Degeneração Neural , Regeneração Nervosa , ParalisiaRESUMO
No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration.
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Melatonina , Traumatismos dos Nervos Periféricos , Ratos , Camundongos , Animais , Traumatismos dos Nervos Periféricos/metabolismo , Melatonina/metabolismo , Estudos Prospectivos , Estudos Retrospectivos , Nervos Periféricos , Nervo Isquiático/metabolismo , Regeneração Nervosa , AutofagiaRESUMO
Ketone bodies (KBs), such as acetoacetate and ß-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.
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Lesões Encefálicas , Dieta Cetogênica , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Humanos , Corpos Cetônicos , Neuroproteção , Fármacos Neuroprotetores/uso terapêutico , Infarto CerebralRESUMO
Due to the limitations of organic liquid electrolytes, current development is towards high performance all-solid-state lithium batteries (ASSLBs). For high performance ASSLBs, the most crucial is the high ion-conducting solid electrolyte (SE), with a focus on interface analysis between SE and active materials. In the current study, we successfully synthesized the high ion-conductive argyrodite-type (Li6PS5Cl) solid electrolyte, which has 4.8 mS cm-1 conductivity at room temperature. Additionally, the present study suggests the quantitative analysis of interfaces in ASSLBs. The measured initial discharge capacity of a single particle confined in a microcavity electrode was 1.05 nAh for LiNi0.6Co0.2Mn0.2O2 (NCM622)-Li6PS5Cl solid electrolyte materials. The initial cycle result shows the irreversible nature of active material due to the formation of the solid electrolyte interphase (SEI) layer on the surface of the active particle; further second and third cycles demonstrate high reversibility and good stability. Furthermore, the electrochemical kinetic parameters were calculated through the Tafel plot analysis. From the Tafel plot, it is seen that asymmetry increases gradually at high discharge currents and depths, which rise asymmetricity due to the increasing of the conduction barrier. However, the electrochemical parameters confirm the increasing conduction barrier with increased charge transfer resistance.
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The renal cortical thickness (RCT) has been correlated with renal function. Previous studies have also reported that the RCT:Abdominal aorta(Ao) ratio is constant in normal dogs with various physical factors. This multi-center, retrospective, analytical study aimed to determine if there are differences between actual RCT and predicted value of RCT considering physical factors in dogs with acute or chronic renal disease. We also aimed to demonstrate whether the RCT and Ao ratio index would be useful for evaluating renal pathology. A total of 54 dogs with acute or chronic renal disease and 30 normal healthy dogs were included in this study. The RCT was measured at the center of the renal pyramid as the shortest distance perpendicular to the renal capsule from the base of the renal medullary pyramid at three points. The diameter of the Ao was measured just caudal to the branch of the left renal artery in the sagittal plane in systole. The RCT:Ao ratio of chronic kidney disease (CKD) patients was 0.50 ± 0.11 (mean ± standard deviation). The RCT:Ao ratio in normal dogs was 0.67 ± 0.07. The RCT:Ao ratio in patients with acute kidney injury (AKI) was 0.83 ± 0.05. There was a statistically significant difference between normal dogs and dogs with CKD (P < 0.001) and between normal dogs and dogs with AKI (P < 0.001). In conclusion, findings from the current study supported using the RCT:Ao ratio as a non-invasive quantitative method for characterizing kidney pathology in dogs with acute or chronic renal disease.