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OBJECTIVE: To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED). MATERIALS AND METHODS: This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences. RESULTS: In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p < .05). The high-potency steroid group had more favourable symptom (p = .035) and sign (p < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom (p = .025) and sign (p = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p > .05). CONCLUSIONS: Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.
High-potency steroid plus CsA is more effective than CsA monotherapy in alleviating the signs and symptoms of DED.Dual therapy has acceptable safety particularly in terms of IOP and cataract risk.Dual therapy is a viable option for patients with severe DED without contraindications.
Subject(s)
Cyclosporine , Drug Therapy, Combination , Dry Eye Syndromes , Humans , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/diagnosis , Male , Female , Retrospective Studies , Middle Aged , Aged , Treatment Outcome , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Adult , Severity of Illness Index , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effectsABSTRACT
Dragon's blood () is a traditional Chinese medicine known for its wound hemostasis, blood circulation, and stasis properties. Recently, it has also been utilized in cosmetics, though its antioxidant capacity remains unclear. This study aims to stabilize the bioactivity of dragon's blood using various plant extracts. We evaluated single plant extracts and their combinations to identify the conditions that maintained the antioxidant capacity of dragon's blood the longest. Selected plants included Hibiscus sabdariffa, Clitoria ternatea, Hylocereus sp., Pandanus amaryllifolius, and Camellia sinensis. We used two sources of dragon's blood: Daemonorops draco and Dracaena cochinchinensis. Extraction conditions were optimized and antioxidant activity was assessed using the free radical scavenging ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH), total anthocyanin concentration (TAC), total polyphenol content (TPC), the free radical scavenging activity of ABTS, and a ferric reducing antioxidant power (FRAP) assay. The results showed that all plant extracts exhibited high antioxidant capacity. Clitoria ternatea had the highest DPPH scavenging ability at 93.81%, with the best combination being green tea and Daemonorops draco at 92.57%. Clitoria ternatea had the highest TPC at 9921 mg GAE/100 g, with the best combination (green tea and Dracaena cochinchinensis) at 10500 mg GAE/100 g. ABTS activity was highest for green tea at 98.3%, with the best combination (Clitoria ternatea and Daemonorops draco) at 93.29%. The FRAP assay showed that green tea had the highest electron-donating potential at 3.85 mg/mL, with the best combination (Daemonorops draco and Dracaena cochinchinensis) at 3.71 mg/mL. This study advances our understanding of the antioxidant properties of these plants and the traditional Chinese medicine dragon's blood, enhancing the efficacy of dragon's blood in skincare and cosmetics. Moreover, the application of these extracts could rejuvenate local agriculture, impacting the skincare, cosmetics, and sustainable agriculture sectors.
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OBJECTIVES: This study was designed to determine the incidence, contributing factors, and prognostic implications of acute kidney injury (AKI) recovery patterns in patients who experienced AKI after valve replacement surgery (VRS). DESIGN: A retrospective cohort study was conducted. SETTING: The work took place in a postoperative care center in a single large-volume cardiovascular center. PARTICIPANTS: Patients undergoing VRS between January 2010 and December 2019 were enrolled. INTERVENTION: Patients were categorized into three groups based on their postoperative AKI status: non-AKI, AKI with early recovery (less than 48 hours), and persistent AKI. MEASUREMENT AND MAIN RESULTS: The primary outcome was in-hospital major adverse clinical events. The secondary outcomes included in-hospital and 1-year mortality. A total of 4,161 patients who developed AKI following VRS were included. Of these, 1,513 (36.4%) did not develop postoperative AKI, 1,875 (45.1%) experienced AKI with early recovery, and 773 (18.6%) had persistent AKI. Advanced age, diabetes, New York Heart Association III-IV heart failure, moderate-to-severe renal dysfunction, anemia, and AKI stages 2 and 3 were identified as independent risk factors for persistent AKI. In-hospital major adverse clinical events occurred in 59 (3.9%) patients without AKI, 88 (4.7%) with early AKI recovery, and 159 (20.6%) with persistent AKI (p < 0.001). Persistent AKI was independently associated with an increased risk of in-hospital adverse events and 1-year mortality. In contrast, AKI with early recovery did not pose additional risk compared with non-AKI patients. CONCLUSIONS: In patients who develop AKI following VRS, early AKI recovery does not pose additional risk compared with non-AKI. However, AKI lasting more than 48 hours is associated with an increased risk of in-hospital and long-term adverse outcomes.
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Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC. Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: ⢠CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. ⢠NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: ⢠CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. ⢠Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.
Subject(s)
Enterocolitis, Necrotizing , Heart Defects, Congenital , Humans , Enterocolitis, Necrotizing/epidemiology , Enterocolitis, Necrotizing/mortality , Enterocolitis, Necrotizing/complications , Infant, Newborn , Male , Female , Heart Defects, Congenital/complications , Heart Defects, Congenital/mortality , Infant, Premature, Diseases/mortality , Infant, Premature, Diseases/epidemiology , Ductus Arteriosus, Patent/complications , Ductus Arteriosus, Patent/epidemiology , Cohort Studies , Risk Factors , Intensive Care Units, Neonatal/statistics & numerical data , China/epidemiology , Infant, Premature , Retrospective StudiesABSTRACT
Tuberculosis (TB) is the number one infectious disease cause of death worldwide due to an incomplete understanding of immunity. Emerging data highlight antibody functions mediated by the Fc domain as immune correlates. However, the mechanisms by which antibody functions impact the causative agent Mycobacterium tuberculosis (Mtb) are unclear. Here, we examine how antigen specificity determined by the Fab domain shapes Fc effector functions against Mtb. Using the critical structural and secreted virulence proteins Mtb cell wall and ESAT-6 & CFP-10, we observe that antigen specificity alters subclass, antibody post-translational glycosylation, and Fc effector functions in TB patients. Moreover, Mtb cell wall IgG3 enhances disease through opsonophagocytosis of extracellular Mtb . In contrast, polyclonal and a human monoclonal IgG1 we generated targeting ESAT-6 & CFP-10 inhibit intracellular Mtb . These data show that antibodies have multiple roles in TB and antigen specificity is a critical determinant of the protective and pathogenic capacity.
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Catalytic therapy based on nanozymes is promising for the treatment of bacterial infections. However, its therapeutic efficacy is usually restricted by the limited amount of hydrogen peroxide and the weak acidic environment in infected tissues. To solve these issues, we prepared polyvinyl alcohol (PVA)-polyacrylic acid (PAA)-iron oxide (Fe3O4)/polyvinyl alcohol (PVA)-zinc peroxide (ZnO2) double-layer electrospun nanofibers (PPF/PZ NFs). In this design, PVA serves as the carrier for ZnO2 nanoparticles (NPs), Fe3O4 NPs, and PAA. The double-layer structure of nanofibers can spatially separate the PAA and ZnO2 to avoid their reaction with each other during preparation and storage, while in the wet wound bed, PVA can dissolve and PAA can provide H+ ions to promote the generation of hydrogen peroxide and subsequent conversion to hydroxyl radicals for bacteria killing. In vitro experimental results demonstrated that PPF/PZ NFs can reduce the methicillin-resistant Staphylococcus aureus by 3.1 log (99.92%). Moreover, PPF/PZ NFs can efficiently treat the bacterial infection in a mouse wound model and promote wound healing with negligible toxicity to animals, indicating their potential use as "plug-and-play" antibacterial wound dressings. This work provides a novel strategy for the construction of double-layer electrospun nanofibers as catalytic wound dressings with hydrogen peroxide/acid self-supplying properties for the efficient treatment of bacterial infections.
Subject(s)
Anti-Bacterial Agents , Hydrogen Peroxide , Methicillin-Resistant Staphylococcus aureus , Nanofibers , Wound Infection , Zinc Oxide , Nanofibers/chemistry , Animals , Mice , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/pharmacology , Catalysis , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Wound Infection/drug therapy , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Polyvinyl Alcohol/chemistry , Acrylic Resins/chemistry , Acrylic Resins/pharmacology , Wound Healing/drug effects , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapy , Particle SizeABSTRACT
BACKGROUND: Tuberculosis (TB) poses a major public health challenge, particularly in children. A substantial proportion of children with TB disease remain undetected and unconfirmed. Therefore, there is an urgent need for a highly sensitive point-of-care test. This study aims to assess the performance of serological assays based on various antigen targets and antibody properties in distinguishing children (0-18 years) with TB disease (1) from healthy TB-exposed children, (2) children with non-TB lower respiratory tract infections, and (3) from children with TB infection. METHODS: The study will use biobanked plasma samples collected from three prospective multicentric diagnostic observational studies: the Childhood TB in Switzerland (CITRUS) study, the Pediatric TB Research Network in Spain (pTBred), and the Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infections in children and adolescents (ProPAED) study. Included are children diagnosed with TB disease or infection, healthy TB-exposed children, and sick children with non-TB lower respiratory tract infection. Serological multiplex assays will be performed to identify M. tuberculosis antigen-specific antibody features, including isotypes, subclasses, Fc receptor (FcR) binding, and IgG glycosylation. DISCUSSION: The findings from this study will help to design serological assays for diagnosing TB disease in children. Importantly, those assays could easily be developed as low-cost point-of-care tests, thereby offering a potential solution for resource-constrained settings. GOV IDENTIFIER: NCT03044509.
Subject(s)
Serologic Tests , Tuberculosis , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Mycobacterium tuberculosis/immunology , Point-of-Care Testing , Prospective Studies , Serologic Tests/methods , Spain , Switzerland , Tuberculosis/diagnosis , Tuberculosis/bloodABSTRACT
Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is over 90% in BC patients, but once BC cells metastasis into distal organs, it is dramatically decreasing to less than 30%. Especially, triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. Understanding the underline mechanisms of TNBC metastasis is a critical issue. Non-coding RNAs, including of lncRNAs and microRNAs, are non-protein-coding transcripts and have been reported as important regulators in TNBC metastasis. However, the underline mechanisms for non-coding RNAs regulating TNBC metastasis remain largely unclear. Here, we found that lncRNA MIR4500HG003 was highly expressed in highly metastatic MDA-MB-231 TNBC cells and overexpression of MIR4500HG003 enhanced metastasis ability in vitro and in vivo and promoted MMP9 expression. Furthermore, we found MIR4500HG003 physically interacted with miR-483-3p and reporter assay showed miR-483-3p attenuated MMP9 expression. Importantly, endogenous high expressions of MIR4500HG003 were correlated with tumor recurrence in TNBC patients with tumor metastasis. Taken together, our findings suggested that MIR4500HG003 promotes metastasis of TNBC through miR-483-3p-MMP9 signaling axis and may be used as potential prognostic marker for TNBC patients.
Subject(s)
Gene Expression Regulation, Neoplastic , Matrix Metalloproteinase 9 , MicroRNAs , Neoplasm Metastasis , RNA, Long Noncoding , Triple Negative Breast Neoplasms , Humans , MicroRNAs/metabolism , MicroRNAs/genetics , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Female , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Cell Line, Tumor , Animals , Mice , Mice, Nude , Cell Movement/genetics , Mice, Inbred BALB CABSTRACT
Background: Healthcare databases play a crucial role in improving our understanding of glaucoma epidemiology, which is the leading cause of irreversible blindness globally. However, the accuracy of diagnostic codes used in these databases to detect glaucoma is still uncertain. Aim: To assess the accuracy of ICD-9-CM and ICD-10-CM codes in identifying patients with glaucoma, including two distinct subtypes, primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Methods: We analyzed electronic medical records data from a 2% random sample of patients who newly underwent visual field examination in Taiwan's largest multi-institutional healthcare system from 2011 to 2020. The diagnosis of glaucoma was confirmed by two ophthalmologists, based on the glaucoma diagnostic criteria. The positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for ICD-9-CM codes 365.1X and 365.2X, and ICD-10-CM codes H4010X, H4011X, H4012X, H4020X, H4021X, H4022X, H4023X and H4024X for glaucoma were calculated. Results: We randomly selected 821 patients (mean age: 56.9 years old; female: 50.5%) from the original cohort of 41,050 newly receiving visual field examination in the study. Among 464 cases with an ICD-9-CM glaucoma code, the sensitivity, specificity, PPV and NPV for glaucoma were 86.5, 96.5, 91.9, and 90.9%, respectively. Among 357 cases with an ICD-10-CM glaucoma code, the sensitivity, specificity, PPV and NPV for glaucoma were 87.0, 92.8, 92.2 and 87.9%, respectively. The accuracy of diagnostic codes to identify POAG and PACG remained consistent. Conclusion: The diagnostic codes were highly reliable for identifying cases of glaucoma in Taiwan's routine healthcare practice. These results provide confidence when using ICD-9-CM and ICD-10-CM codes to define glaucoma cases in healthcare database research in Taiwan.
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Postoperative cognitive dysfunction (POCD) is a common complication following surgery, adversely impacting patients' recovery, increasing the risk of negative outcomes, prolonged hospitalization, and higher mortality rates. The N-methyl-D-aspartate (NMDA) receptor, crucial for learning, memory, and synaptic plasticity, plays a significant role in the development of POCD. Various perioperative factors, including age and anesthetic use, can reduce NMDA receptor function, while surgical stress, inflammation, and pain may lead to its excessive activation. This review consolidates preclinical and clinical research to explore the intricate relationship between perioperative factors affecting NMDA receptor functionality and the onset of POCD. It discusses the influence of aging, anesthetic administration, perioperative injury, pain, and inflammation on the NMDA receptor-related pathophysiology of POCD. The comprehensive analysis presented aims to identify effective treatment targets for POCD, contributing to the improvement of patient outcomes post-surgery.
Subject(s)
Anesthetics , Cognitive Dysfunction , Postoperative Cognitive Complications , Humans , Postoperative Cognitive Complications/etiology , Receptors, N-Methyl-D-Aspartate , Pain/complications , Inflammation/complications , Postoperative Complications/etiology , Cognitive Dysfunction/complicationsABSTRACT
Near-infrared (NIR) chromophores with analyte tunable emission and absorption properties are highly desirable for developing activatable fluorescence and photoacoustic (PA) probes for bioimaging and disease diagnosis. Here we engineer a class of new chromophores by extending the π-conjugation system of a xanthene scaffold at position 7 with different electron withdrawing groups. It is demonstrated that these chromophores exhibit pH-dependent transition from a spirocyclic "closed" form to a xanthene "open" form with remarkable changes in spectral properties. We further develop fluorescence and PA probes by caging the NIR xanthene chromophores with a dipeptidyl peptidase 4 (DPPIV) substrate. In vitro and live cell studies show that these probes allow activatable fluorescence and PA detection and imaging of DPPIV activity with high sensitivity, high specificity and fast response. Moreover, these two probes allow high-contrast and highly specific imaging of DPPIV activity in a tumour-bearing mouse model in vivo via systemic administration. This study highlights the potential of a xanthene scaffold as a versatile platform for developing high-contrast fluorescence and PA molecular probes.
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Cystatins comprise a vast superfamily of evolutionary conserved proteins, predominantly recognized for their roles as endogenous inhibitors by regulating the activity of cysteine proteases. Emerging lines of research evidence also provides insight into their alternative roles in a spectrum of biological and pathological processes, including neurodegenerative disorders, tumor progression, inflammatory diseases, and immune response. Nowadays, various type-1 cystatins (stefins) have been demonstrated among a variety of discovered vertebrate groups, while little is known about the related homologue in cephalochordate amphioxus, which are repositioned at the base of the chordate phylum. In the present study, a single type-1 cystatin homologue in Branchiostoma japonicum was first successfully cloned and designated as Bjcystatin-1. The deduced Bjcystatin-1 protein is structurally characterized by the presence of typical wedge-shaped cystatin features, including the 'QxVxG' and 'Px' motif, as well as the conserved N-terminal glycine residue. Phylogenomic analyses utilizing different cystatin counterparts affirmed the close evolutionary relationship of Bjcystatin-1 and type-1 cystatin homologue. Bjcystatin-1 was predominantly expressed in the gills and hind-gut in a tissue-specific pattern, and its expression was remarkably up-regulated in response to challenge with bacteria or their signature molecules LPS and LTA, suggesting the involvement in immune response. Additionally, the recombinant Bjcystatin-1 (rBjcystatin-1) protein showed significant inhibitory activity towards papain and binding ability to LPS and LTA, indicating its hypothesized role as a pattern recognition receptor in immune response. Subcellular localization results also showed that Bjcystatin-1 was located in the cytoplasm and nucleus, and its overexpression could attenuate the activation of LPS-induced nuclear transcription factors NF-κB. Taken together, our study suggests that amphioxus Bjcystatin-1 acts as a dual role in protease inhibitor and an immunocompetent factor, providing new insights into the immune defense effect of type-1 cystatin in amphioxus.
Subject(s)
Cystatins , Lancelets , Animals , Lipopolysaccharides , Cystatins/genetics , Biological Evolution , Transcription FactorsABSTRACT
AIM: To provide the direct evidence for the crucial role of trimethylamine N-oxide (TMAO) in vascular permeability and endothelial cell dysfunction under diabetic condition. METHODS: The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells (HRMEC) under high glucose conditions was tested by a cell counting kit, wound healing, a transwell and a tube formation assay. The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction (RT-PCR). The expression of the cell junction was measured by Western blotting (WB) and immunofluorescence staining. In addition, two groups of rat models, diabetic and non-diabetic, were fed with normal or 0.1% TMAO for 16wk, and their plasma levels of TMAO, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were tested. The vascular permeability of rat retinas was measured using FITC-Dextran, and the expression of zonula occludens (ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining. RESULTS: TMAO administration significantly increased the cell proliferation, migration, and tube formation of primary HRMEC either in normal or high-glucose conditions. RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation, while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment. Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage, which were even higher in TMAO-feeding diabetic rats. Furthermore, TMAO administration increased the rat plasma levels of VEGF, IL-6 and TNF-α while decreasing the retinal expression levels of ZO-1 and claudin-5. CONCLUSION: TMAO enhances the proliferation, migration, and tube formation of HRMEC, as well as destroys their vascular integrity and tight connection. It also regulates the expression of VEGF, IL-6, and TNF-α.
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Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).
Subject(s)
Deferoxamine , Ototoxicity , Humans , tert-Butylhydroperoxide/toxicity , tert-Butylhydroperoxide/metabolism , Deferoxamine/pharmacology , Ototoxicity/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Hair Cells, Auditory/metabolism , Iron/metabolismABSTRACT
BACKGROUND: Acne scars present a complex challenge in dermatology and cosmetics, despite advancements in technological interventions such as fractional lasers, microneedling, and surgical procedures. Effective treatment remains elusive for many individuals. OBJECTIVE: This study aims to evaluate the efficacy of rotational fractional resection using 1 mm diameter rotating scalpels as a primary treatment for icepick and boxcar scars on the cheeks and glabella region. METHODS: Three patients with acne scars underwent a single treatment session of rotational fractional resection. Evaluation occurred at the 2-month post-treatment mark to assess improvements in scar appearance and potential skin-related side effects. RESULTS: Following the treatment, significant improvements were observed in the targeted acne scars. Notable enhancements were noted without major skin-related adverse effects, except for minor suture marks. CONCLUSION: The outcomes of this study underscore the potential of rotational fractional resection as an innovative and effective approach in treating acne scars. This single-session cosmetic procedure shows promise in yielding lasting and quantifiable results, offering a hopeful solution for individuals seeking comprehensive acne scar treatment.
Subject(s)
Acne Vulgaris , Cicatrix , Humans , Cicatrix/etiology , Cicatrix/surgery , Acne Vulgaris/complications , Acne Vulgaris/therapy , Skin/pathology , Treatment OutcomeABSTRACT
PURPOSE: To assess the effects of ceramic thickness, ceramic translucency, and light transmission on restorative composites used as luting cement for lithium disilicate-based ceramics. METHODS: Four luting types of cement were tested (n=8); a dual-cured resin cement (Multilink N), a light-cured conventional flowable composite (Tetric N-Flow), and two light-cured bulk-fill flowable composites (Tetric N-Flow Bulk Fill and X-tra base). The 20 s- or 40 s-light (1000 mW/cm2) was transmitted through 1- or 2-mm-thick high- or low-translucency (HT- or LT-) ceramic discs (IPS e.Max press) to reach the 1-mm-thick luting cement. Light transmitted to cement without ceramic served as a control. Vickers hardness number (VHN), flexural strength (FS), fractography, and degree of conversion (DC) were evaluated. One-way and multi-way analysis of variance was conducted to determine the effects of factors on VHN and FS. RESULTS: Ceramic thickness, light transmission time, and cement type significantly affected the VHN of the luting cement (P < .000). Only Multilink N (LT- and HT-1mm) and Tetric N-Flow (HT-1mm) reached 90% VHN of corresponding control by 20 s-light transmissions, but Tetric N-Flow exhibited lowest VHN and approximately 1/3-1/2 VHN of Multilink N (P < 0.05). X-tra base expressed superior physicochemical properties to Tetric N-Flow Bulk Fill (P < 0.05) and reached >90% VHN of control in all conditions with 40 s-light transmissions except for LT-2 mm. DC, FS, and fractography supported these findings. CONCLUSIONS: The light-cured bulk-fill composite served as a luting cement for lithium-disilicate-based ceramics in a product-dependent manner. Light transmission time is crucial to ensure sufficient luting cement polymerization.
Subject(s)
Ceramics , Dental Porcelain , Dental Porcelain/chemistry , Ceramics/chemistry , Dental Cements , Resin Cements/chemistry , Hardness , Materials Testing , Surface PropertiesABSTRACT
Maternal immunity impacts the infant, but how is unclear. To understand the implications of the immune exposures of vaccination and infection in pregnancy for neonatal immunity, we evaluated antibody functions in paired peripheral maternal and cord blood. We compared those who in pregnancy received mRNA coronavirus disease 2019 (COVID-19) vaccine, were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the combination. We found that vaccination enriched a subset of neutralizing activities and Fc effector functions that was driven by IgG1 and was minimally impacted by antibody glycosylation in maternal blood. In paired cord blood, maternal vaccination also enhanced IgG1. However, Fc effector functions compared to neutralizing activities were preferentially transferred. Moreover, changes in IgG posttranslational glycosylation contributed more to cord than peripheral maternal blood antibody functional potency. These differences were enhanced with the combination of vaccination and infection as compared to either alone. Thus, Fc effector functions and antibody glycosylation highlight underexplored maternal opportunities to safeguard newborns.
Subject(s)
COVID-19 , Infant, Newborn , Infant , Female , Pregnancy , Humans , COVID-19/prevention & control , SARS-CoV-2 , Immunoglobulin G , COVID-19 Vaccines , Vaccination , Antibodies, ViralABSTRACT
PURPOSE: To examine the initial presenting symptoms in relation to sex and identify predictors of discordance between symptoms and signs of dry eye disease (DED) in Taiwan. DESIGN: Retrospective cross-sectional study. METHODS: This clinic-based cohort from a tertiary referral center in Taiwan included 1229 patients diagnosed with DED at Keelung Chang Gung Memorial Hospital in Taiwan between August 1, 2011, and July 31, 2018. Initial presenting symptoms were cross-sectionally and retrospectively collected. The composite score, indicating the discordance between symptoms and signs, was derived from the difference between the DED symptom severity score and the DED sign severity score. RESULTS: Of 1229 patients, 975 (79.3%) were female, with a mean age of 56.7 ± 14.9 years. Initial presenting symptoms didn't show significant sex differences (all P > .05). In multivariate analysis, predictors of higher symptom severity score than sign severity score included being female (P = .011) and having a surgical history of cataract (P = .037), pterygium, or conjunctivochalasis (P = .014). Conversely, older age (P < .001) and artificial tear use (P < .001) were significant predictors of a lower symptom severity score than sign severity score. CONCLUSIONS: Strong predictors of incongruity between DED symptoms and signs include age, gender, surgical history for cataract, pterygium or conjunctivochalasis, and artificial tear use. Ophthalmologists should prioritize symptoms for female patients and postsurgery cases. In addition, the absence of symptoms should not dismiss DED possibility in older adult patients and those using artificial tears. Notably, early recognition and enhancement of postoperative care can improve patient satisfaction and quality of life.