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Underground small indoor gymnasiums (USIG) are important public places, it is vital to design and build a very economical and efficient ventilation system for effective closed-loop regulation of temperature and gases concentration at prescribed levels. In the article, the model-based prototype design, establishment and operation were proposed and applied to closed-loop control system of the underground small indoor gymnasiums' ventilation system (USIGVS). First of all, the extended Multiphysics model was developed through feedback connecting the 3D Multiphysics model of air flow rate, temperature, O2 and CO2 concentration with a 0D proportional-integral-derivative (PID) controller via Neumann boundary condition, hence a close-loop USIGVS was constructed for feedback control of temperature and gases concentration in ping-pong USIG. Simultaneously, a cost function sufficiently representing the design requirement was formulated. Then global parameter sensitivity analysis (GPSA) was applied for sensitivity ranking of parameters including geometric parameters of USIGVS and tunable parameters of PID controller. The GPSA proved that sensitivity ordering of the cost function to each parameter was proportional gain (k p ) > derivative gain (k d ) > distance from left inlet to bottom (r) > distance from outlet pipe to bottom (d) > integrative gain (k i ) > distance from upper inlet pipe to left (h), respectively, and the k p , k d and r was the parameter influencing the cost function the most. The optimal parameters determined by both GPSA and response optimization were k p = 3.17 m4 mol-1 s-1, k d = 1.49 m4 mol-1, r = 2.04 m, d = 3.12 m, k i = 0.37 m4 mol-1 s-2 and h = 3.85 m. Finally, the closed-loop USIGVS prototype with optimal parameters was designed and established through real-time simulation. The real-time operation confirmed that the temperature and gases concentrations were robust maintained at prescribed levels with desired dynamic response characteristics and lower power consumption, and the expected requirements were achieved for the design, establishment and operation of closed-loop USIGVS control system prototype.
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This paper presents the findings of an observational study involving 38 patients to evaluate the application of a surgical technique utilizing an autologous costal cartilage scaffold for correcting nasal tip and alar asymmetry in unilateral cleft lip-nasal deformity. Nasal septum extension spreader grafts (SEG) and warped alar batten grafts, both made from autologous costal cartilage, were utilized in open rhinoplasty procedures. The warped alar batten graft was fixed to the caudal end of the SEG, with the lower lateral cartilage on the cleft side suspended to the free part of the newly created warped alar batten graft to lift the collapsed nasal alar further. Measurements of nasal tip height, nostril height, and the intersection angle of the nasal sill and alar (α) were taken before and after surgery, comparing the ratios between the normal and cleft sides. Patients were followed up for 2.5 to 5.5 years, with all cases showing successful healing and no complications. Postoperative improvements in nasal tip and nostril asymmetries were significant, with statistically significant changes observed in nasal tip height, nostril height, and the intersection angle of nasal sill and alar (α) (P<0.05). The combined use of SEG and warped alar batten graft, both crafted from autologous costal cartilage, effectively corrected nasal tip and alar asymmetry in adult cleft lip nasal deformity cases.
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This study aimed to explore the relationship between female age and pregnancy outcomes in patients undergoing their first elective single embryo transfer (eSET) of in vitro fertilization (IVF) cycles. The retrospective cohort study encompassed 7089 IVF/intracytoplasmic sperm injection (ICSI) patients of the Reproductive Medicine Center, Henan Provincial Peoples' Hospital of China, from September 1, 2016, to May 31, 2022. Patients all received the first eSET in their IVF/ICSI cycles. A generalized additive model (GAM) was employed to examine the the dose-response correlation between age and pregnancy outcomes, namely the clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR). Logistic regression model was employed to ascertain the correlation between the CPR/OPR and age. The study cohort has an average age of 30.74; 3843 patients got clinical pregnancy rate of 61.40% and ongoing pregnancy rate of 54.21%. The multiple pregnancy rate of is 1.24%. For patients aged 34 and above, the CPR decreased by 10% for every 1-year increase in age (adjusted OR 0.90, 95% CI 0.84-0.96, p < 0.0001). Similarly, the OPR decreased by 16% for every 1-year increase in age (adjusted OR 0.84, 95% CI 0.81-0.88, p < 0.0001). Patients aged 35-37 years had an acceptable OPR of 52.4% after eSET, with a low multiple pregnancy rate (1.1%). Pregnancy outcomes were significantly better in blastocyst cycles compared to cleavage embryo cycles, and this trend was more pronounced in older patients. There was a non-linear relationship between female age and pregnancy outcomes in patients undergoing their first eSET cycles. The clinical pregnancy rate and ongoing pregnancy rate decreased significantly with age, especially in women older than 34 years. For patients under 37 years old, single embryo transfer should be prioritized. For patients over 38 years old with available blastocysts, eSET is also recommended.
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Resultado del Embarazo , Índice de Embarazo , Transferencia de un Solo Embrión , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Fertilización In Vitro/métodos , Factores de Edad , China , Inyecciones de Esperma Intracitoplasmáticas/métodos , Edad MaternaRESUMEN
Osteoarthritis (OA) is a degenerative disease commonly seen in middle-aged and elderly people. Multiple cytokines are involved in the local tissue damage in OA. Currently, non-pharmacologic and surgical interventions are the main conventional approaches for the treatment of OA. In terms of pharmaceutical drug therapy, NSAIDs and acetaminophen are mainly used to treat OA. However, it is prone to various adverse reactions such as digestive tract ulcer, thromboembolism, prosthesis loosening, nerve injury and so on. With the in-depth study of OA, more and more novel topical drug delivery strategies and vehicles have been developed, which can make up for the shortcomings of traditional dosage forms, improve the bioavailability of drugs, and significantly reduce drug side effects. This review summarizes the immunopathogenesis, treatment guidelines, and progress and challenges of topical delivery technologies of OA, with some perspectives on the future pharmacological treatment of OA proposed.
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Antiinflamatorios no Esteroideos , Sistemas de Liberación de Medicamentos , Osteoartritis , Humanos , Osteoartritis/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Antiinflamatorios no Esteroideos/administración & dosificación , Administración Tópica , Acetaminofén/administración & dosificación , Animales , Disponibilidad BiológicaRESUMEN
AIM: Patients with rheumatoid arthritis (RA) are at a higher risk of osteoporotic fractures. Studies have shown that patients with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE) experienced an increase in bone mineral density (BMD) after receiving hydroxychloroquine (HCQ) treatment, indicating a potential protective effect against osteoporosis. Therefore, this study is to examine the relationship between HCQ usage and the risk of osteoporosis in patients diagnosed with RA. METHODS: The retrospective cohort study used data from Taiwan's National Health Insurance Research Database (NHIRD) covering the period from January 2010 to December 2018, which included 14 050 newly diagnosed RA patients, subsequently divided into two groups: HCQ users and non-users. Propensity score matching (PSM) based on sex, age, urbanization, insured unit type, insured area, and comorbidities was conducted to match the groups. The primary outcome assessed was the evaluation of the risk of osteoporosis by employing a multivariable Cox proportional hazard regression model to calculate the adjusted hazard ratio (aHR). RESULTS: After PSM, a total of 6408 RA patients were included in the analysis (3204 HCQ users and 3204 non-users). There was no significantly higher risk of osteoporosis in HCQ users compared with non-users, aHR = 0.99 (95% CI: 0.82-1.196). Additionally, different durations of HCQ usage demonstrated a neutral effect on the risk of osteoporosis [HCQ <90 days, aHR = 0.88 (95% CI: 0.585-1.324); HCQ 90-180 days, aHR = 0.941 (95% CI: 0.625-1.418); HCQ >180 days, aHR = 1.019 (95% CI: 0.832-1.249)]. CONCLUSIONS: The study indicates that there is no significant association between the use of HCQ and the risk of osteoporosis in patients with RA.
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Antirreumáticos , Artritis Reumatoide , Bases de Datos Factuales , Hidroxicloroquina , Osteoporosis , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/diagnóstico , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Estudios Retrospectivos , Osteoporosis/epidemiología , Osteoporosis/inducido químicamente , Osteoporosis/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Antirreumáticos/efectos adversos , Taiwán/epidemiología , Factores de Riesgo , Adulto , Anciano , Medición de Riesgo , Densidad Ósea/efectos de los fármacos , Resultado del Tratamiento , Factores de Tiempo , Factores ProtectoresRESUMEN
Oligodendrocyte myelination and remyelination after injury are intricately regulated by various intrinsic and extrinsic factors, including transcriptional regulators. Among these, the zinc-finger protein ZFP488 is an oligodendrocyte-enriched transcriptional regulator that promotes oligodendrocyte differentiation in the developing neural tube and in oligodendroglial cell lines. However, the specific in vivo genetic requirements for ZFP488 during oligodendrocyte development and remyelination have not been defined. To address this gap, we generated a lineage-traceable ZFP488 knock-out mouse line, wherein a H2b-GFP reporter replaces the ZFP488-coding region. Using these mice of either sex, we examined the dynamics of ZFP488 expression from the endogenous promoter in the developing central nervous system (CNS). We observed a unique expression pattern in the oligodendrocyte lineage, with ZFP488 expression particularly enriched in differentiated oligodendrocytes. ZFP488 loss resulted in delayed myelination in the developing CNS and impaired remyelination after demyelinating injury in the brain. Integrated transcriptomic and genomic profiling further revealed that ZFP488 loss decreased expression of myelination-associated genes but not oligodendrocyte progenitor-associated genes, suggesting that ZFP488 serves as a positive regulator of myelination by regulating maturation programs. Thus, our genetic loss-of-function study revealed that ZFP488 regulates a stage-dependent differentiation program that controls the timing of CNS myelination and remyelination.Significance statement Precise timing of myelination is essential for efficient neural communication and is linked to the development of cognitive and motor skills as well as myelin repair after injury. ZFP488 is a transcriptional regulator enriched in oligodendrocytes, however its in vivo functions remain unclear. By generating ZFP488 loss-of-function mice, we demonstrated that ZFP488 is critical for the timing of myelination and remyelination and that its loss impaired the initial differentiation of oligodendrocytes but not their precursor formation and proliferation. Transcriptomic profiling showed that ZFP488 functions as a positive regulator of myelination by modulating oligodendrocyte maturation programs. Thus, our findings underscore the important role of ZFP488 in myelination and the potential of ZFP488 augmentation as an avenue to enhance oligodendrocyte regeneration.
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Aging is an inevitable and complex biological process involving multi-factorial mechanisms. Mitochondrial dysfunction is a critical factor in the aging process, characterized by a decline in mitochondrial quality and activity, leading to aging and aging-related diseases. Therefore, mitochondria have become an attractive target in anti-aging therapies. Several senolytic drugs targeting mitochondria and antioxidant agents have been used in anti-aging research in the past few years. However, these strategies may cause adverse effects with long-term medication. In this extensive review, we propose "mitochondrial transplantation," which transfers healthy mitochondria from donor cells to recipient cells to replace damaged or dysfunctional mitochondria, as a new alternative strategy for treating mitochondrial dysfunction and aging-associated diseases. In this review, we introduce the contemporary landscape of mitochondrial transplantation, then discuss intensely the successful applications of mitochondrial transplantation therapy in aging diseases such as neurodegenerative diseases, cardiovascular aging, and reproductive aging, highlighting its translational potential. Finally, we summarize and prospect the challenges and opportunities mitochondrial transplantation faces in anti-aging therapy.
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Geranylgeranyl diphosphate synthase (GGPPS) is the crucial bottleneck in carotenoid biosynthesis. However, low activity limits the broad application of GGPPS. In this study, OsGGPPS1 in rice was engineered based on ancestral sequence reconstruction (ASR) and semirational design to improve the catalytic performances of existing GGPPS. The better mutant of A22R/A26P with improved enzyme activity was generated based on ASR. Additionally, the improved enzyme activity of mutants as V162A/M218S/F227Y was designed using a semirational design. The combinatorial assembly of the d-OsGGPPS1 mutant (A22R/A26P/V162A/M218S/F227Y) exhibited higher conversion of IPP and each cosubstrate of DMAPP for 9.8-fold in GPP production, GPP for 6.4-fold in FPP production, and FPP for 1.4-fold in GGPP production relative to wild-type OsGGPPS1 at 25 °C, which showed higher conversion than wild-type OsGGPPS1 at temperatures as high as 50 °C. The successful design of OsGGPPS1 was representative of protein engineering, which will shed new light on GGPPS engineering and active plant pigment resource utilization.
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Farnesiltransferasa , Oryza , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Farnesiltransferasa/genética , Farnesiltransferasa/metabolismo , Farnesiltransferasa/química , Oryza/genética , Oryza/enzimología , Cinética , Ingeniería de Proteínas , BiocatálisisRESUMEN
OBJECTIVE: To analyze the clinical characteristics of patients with Epstein-Barr virus(EBV)-associated hemophagocytic lymphohistiocytosis(HLH) with acute kidney injury(AKI). METHODS: EBV-HLH patients who were hospitalized in our hospital from January 2014 to December 2020 were collected, and their clinical characteristics, treatment, concurrent acute kidney injury and prognosis were retrospectively analyzed. RESULTS: In this study, the incidence of AKI complicated by EBV-HLH was 65.5%, and the 28-day mortality rate was 15.3%. Compared with non-AKI group, patients in the AKI group had higher levels of bilirubin, lactate dehydrogenase, creatinine, urea nitrogen, and ß2-microglobulinï¼ß2-MGï¼, poorer coagulation, and lower soluble IL-2 receptor ï¼sCD25ï¼. Patients in the AKI group had a higher proportion of chemotherapy, transplantation, mechanical ventilation, and the application of vasoactive medications, and were hospitalized for longer periods of time, with higher in-hospital mortality rates and 28-day mortality rates. Patients in the AKI group were analyzed in subgroups according to the Kidney Disease Improving Global Outcomes ï¼KDIGOï¼classification, and the levels of leukocytes, bilirubin, albumin, creatinine, urea nitrogen, ß2-MG, activated partial thromboplastin time ï¼APTTï¼, and prothrombin time activity ï¼PTAï¼were more responsive to the severity of the patient's condition. KDIGO grade 2 and 3 had higher proportions of receiving transplants, diuretics, organ support (mechanical ventilation, application of vasoactive medications, and renal replacement therapy), and admissions to the intensive care unit ï¼ICUï¼, and with higher in-hospital mortality rates and 28-day mortality rates. Regression analysis found that creatinine, ß2-MG, APTT, transplantation, and chemotherapy were independent risk factors for the development of AKI; the application of vasoactive drugs was both an independent risk factor for the development of AKI and for death at 28 days; and chemotherapy, length of hospitalization, and HGB and fibrinogen levels were protective factors for death at 28 days. CONCLUSION: AKI in EBV-HLH has high incidence and high rate of progression to severe disease and death, early attention should be given and strengthened in order to carry out early treatment and improve the prognosis of patients.
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Lesión Renal Aguda , Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Humanos , Lesión Renal Aguda/etiología , Estudios Retrospectivos , Pronóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Mortalidad Hospitalaria , Femenino , MasculinoRESUMEN
The digestion of starch-based foods in the intestinal tract is important for human health. Modeling the details enhances fundamental understanding and glycemic prediction accuracy. It is, however, a challenge to take granular properties into account. A multiscale digestion model has been proposed to characterize mass transfer and hydrolysis reaction at both the intestine and particle scales, seamlessly integrating inter-scale mass exchange. A specific grid scheme was formulated for the shrinkage and transport of the particle computational domain. By incorporating additional glycemic-related processes, e.g., intestinal absorption, a dietary property-based glycemic prediction system has been developed. Its effectiveness was validated based on a human tolerance experiment of cooked rice particles. The model-based investigation comprehensively reveals the impact of initial size on digestion behavior, specifically in terms of enzyme distribution and particle evolution. This work also demonstrates the significance of modeling both particle-scale diffusion and intestine-scale transport, a combination not previously explored. The results indicate that ignoring the former mechanism leads to an overestimation of the glycemic peak by at least 50.8%, while ignoring the latter results in an underestimation of 16.3%.
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Digestión , Modelos Biológicos , Almidón , Almidón/química , Almidón/metabolismo , Humanos , Oryza/química , Índice Glucémico , Tamaño de la Partícula , Hidrólisis , Absorción IntestinalRESUMEN
Positron emission tomography (PET) targeting translocator protein 18 kDa (TSPO) can be used for the noninvasive detection of neuroinflammation. Improved in vivo stability of a TSPO tracer is beneficial for minimizing the potential confounding effects of radiometabolites. Deuteration represents an important strategy for improving the pharmacokinetics and stability of existing drug molecules in the plasma. This study developed a novel tracer via the deuteration of [18F]LW223 and evaluated its in vivo stability and specific binding in neuroinflammatory rodent models and nonhuman primate (NHP) brains. Compared with LW223, D2-LW223 exhibited improved binding affinity to TSPO. Compared with [18F]LW223, [18F]D2-LW223 has superior physicochemical properties and favorable brain kinetics, with enhanced metabolic stability and reduced defluorination. Preclinical investigations in rodent models of LPS-induced neuroinflammation and cerebral ischemia revealed specific [18F]D2-LW223 binding to TSPO in regions affected by neuroinflammation. Two-tissue compartment model analyses provided excellent model fits and allowed the quantitative mapping of TSPO across the NHP brain. These results indicate that [18F]D2-LW223 holds significant promise for the precise quantification of TSPO expression in neuroinflammatory pathologies of the brain.
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[This corrects the article DOI: 10.3389/fimmu.2022.967040.].
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Rechargeable aqueous Zn-ion batteries have been deemed a promising energy storage device. However, the dendrite growth and side reactions have hindered their practical application. Herein, inspired by the ultrafluidic and K+ ion-sieving flux through enzyme-gated potassium channels (KcsA) in biological plasma membranes, a metal-organic-framework (MOF-5) grafted with -ClO4 groups (MOF-ClO4) as functional enzymes is fabricated to mimic the ultrafluidic lipid-bilayer structure for gating Zn2+ 'on' and anions 'off' states. The MOF-ClO4 achieved perfect Zn2+/SO4 2- selectivity (â¼10), enhanced Zn2+ transfer number ([Formula: see text]) and the ultrafluidic Zn2+ flux (1.9 × 10-3 vs. 1.67 mmol m-2 s-1 for KcsA). The symmetric cells based on MOF-ClO4 achieve a lifespan of over 5400 h at 10 mA cm-2/20 mAh cm-2. Specifically, the performance of the PMCl-Zn//V2O5 pouch cell keeps 81% capacity after 2000 cycles at 1 A g-1. The regulated ion transport, by learning from a biological plasma membrane, opens a new avenue towards ultralong lifespan aqueous batteries.
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Natural disasters bring indelible negative impacts to human beings, and people usually adopt some post hoc strategies to alleviate such impacts. However, the same strategies may have different effects in different countries (or regions), which is rarely paid attention by the academic community. In the context of COVID-19, we examine the effect of distance restriction policies (DRP) on reducing human mobility and thus inhibiting the spread of the virus. By establishing a multi-period difference-in-differences model to analyse the unique panel dataset constructed by 44 countries, we show that DRP does significantly reduce mobility, but the effectiveness varies from country to country. We built a moderating effect model to explain the differences from the cultural perspective and found that DRP can be more effective in reducing human mobility in countries with a lower indulgence index. The results remain robust when different sensitivity analyses are performed. Our conclusions call for governments to adapt their policies to the impact of disasters rather than copy each other.
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COVID-19 , Pandemias , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & controlRESUMEN
Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results. Our results showed that genetically predicted T2D was associated with increased CAVS risk (OR 1.153, 95% CI 1.096-1.214, p < 0.001), and this association persisted even after adjusting for adiposity traits in multivariable MR analysis. Furthermore, the two-step MR analysis identified 69 of 251 candidate mediators that partially mediated the effect of T2D on CAVS, including total branched-chain amino acids (proportion mediated: 23.29%), valine (17.78%), tyrosine (9.68%), systolic blood pressure (8.72%), the triglyceride group (6.07-11.99%), the fatty acid group (4.78-12.82%), and the cholesterol group (3.64-11.56%). This MR study elucidated the causal impact of T2D on CAVS risk independently of adiposity and identified potential mediators in this association pathways. Our findings shed light on the pathogenesis of CAVS and suggest additional targets for the prevention and intervention of CAVS attributed to T2D.
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We and other groups have documented that bone marrow-mesenchymal stem cells (BM-MSCs) from Systemic lupus erythematosus (SLE) patients demonstrated signs of senescence, including reduced ability of regulating Treg. Treg cell defects or Treg cell deficiency are regarded as significant factors in the progression of SLE. Exosomes, nanoscale vesicles, abound in molecular and genetic contents, play a critical role in intercellular communications. The purpose of this research is to investigate the mechanism of MSCs-exosomes regulating Tregs cells in SLE, further elucidate the mechanism of immune dysregulation of aging BM-MSCs, and provide theoretical basis and data support for new targets of SLE treatment. In the study, BM-MSCs and exosomes were isolated successfully. Exosomes could be up-taken by naïve CD4+T cells. MSCs-exosomes attenuated SLE clinical manifestation in vivo, but MSCs-exosomes from SLE patients were ineffective. MSCs-exosomes from SLE patients dysregulated Treg cells differentiation in vivo and in vitro. Exosomal miR-20a-5p contributed to the effect of MSCs-exosomes regulating Treg cells. Up-regulating the expression of miR-20a-5p in SLE MSCs-exosomes can restore their ability to promote Treg differentiation and treatment effect. This study further elucidated the role of in the immunomodulatory mechanism of BM-MSCs-exosomes and provided new ideas for the non-cellular autologous transplantation therapy of SLE.
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Exosomas , Lupus Eritematoso Sistémico , Células Madre Mesenquimatosas , MicroARNs , Linfocitos T Reguladores , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , MicroARNs/genética , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/inmunología , Exosomas/metabolismo , Exosomas/genética , Exosomas/inmunología , Exosomas/trasplante , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Humanos , Animales , Femenino , Diferenciación Celular , Ratones , Trasplante de Células Madre Mesenquimatosas , Adulto , Regulación hacia Arriba , MasculinoRESUMEN
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex chronic pain disorder with an elusive etiology and nonspecific symptoms. Although numerous animal models with phenotypes similar to human disease have been established, no available regimen can consistently alleviate clinical symptoms. This dilemma led us to question whether current animal models adequately represent IC/BPS. We compared four commonly used IC/BPS rat models to determine their diverse histopathological and molecular patterns. Female rats were given single treatments with hydrochloric acid (HCL), acetic acid (AA), protamine sulfate plus lipopolysaccharide (PS + LPS), or cyclophosphamide (CYP) to induce IC/BPS. Bladder sections were stained for histopathologic evaluation, and mRNA expression profiles were examined using next-generation sequencing and gene set analyses. Mast cell counts were significantly higher in the HCL and AA groups than in the PS + LPS, CYP, and control groups, but only the AA group showed significant collagen accumulation. The models differed substantially in terms of their gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our observations suggest that none of these rat models fully reflects the complexity of IC/BPS. We recommend that future studies apply and compare multiple models simultaneously to fully replicate the complicated features of IC/BPS.
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Cistitis Intersticial , Modelos Animales de Enfermedad , Animales , Cistitis Intersticial/patología , Cistitis Intersticial/inducido químicamente , Cistitis Intersticial/metabolismo , Femenino , Ratas , Vejiga Urinaria/patología , Vejiga Urinaria/metabolismo , Vejiga Urinaria/efectos de los fármacos , Ratas Sprague-Dawley , Mastocitos/metabolismo , Ciclofosfamida/efectos adversos , Ácido Clorhídrico/efectos adversos , Ácido Clorhídrico/toxicidad , LipopolisacáridosRESUMEN
Purpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC. Materials and Methods: High-throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated. Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors. Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.
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Reactive oxygen species (ROS), as metabolic byproducts, play pivotal role in physiological and pathological processes. Recently, studies on the regulation of ROS levels for disease treatments have attracted extensive attention, mainly involving the ROS-induced toxicity therapy mediated by ROS producers and antioxidant therapy by ROS scavengers. Nanotechnology advancements have led to the development of numerous nanomaterials with ROS-modulating capabilities, among which carbon dots (CDs) standing out as noteworthy ROS-modulating nanomedicines own their distinctive physicochemical properties, high stability, and excellent biocompatibility. Despite progress in treating ROS-related diseases based on CDs, critical issues such as rational design principles for their regulation remain underexplored. The primary cause of these issues may stem from the intricate amalgamation of core structure, defects, and surface states, inherent to CDs, which poses challenges in establishing a consistent generalization. This review succinctly summarizes the recently progress of ROS-modulated approaches using CDs in disease treatment. Specifically, it investigates established therapeutic strategies based on CDs-regulated ROS, emphasizing the interplay between intrinsic structure and ROS generation or scavenging ability. The conclusion raises several unresolved key scientific issues and prominent technological bottlenecks, and explores future perspectives for the comprehensive development of CDs-based ROS-modulating therapy.