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1.
Nat Commun ; 15(1): 1024, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310093

RESUMO

Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8-11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.


Assuntos
Cartilagem Articular , Osteoartrite , Humanos , Masculino , Animais , Camundongos , Mesalamina/farmacologia , Mesalamina/uso terapêutico , PPAR gama/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Modelos Animais de Doenças
2.
Environ Pollut ; 343: 123270, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38163627

RESUMO

The cross-shelf distributions of total mercury (THg), methylmercury (MeHg) and organic and inorganic matter, as well as the presence of the hgcA gene were investigated on the East Siberian Shelf (ESS) to understand the processes underlying the speciation of sedimentary Hg. Samples were collected from 12 stations grouped into four zones based on water depth: inner shelf (5 stations), mid-shelf (3 stations), outer shelf (2 stations), and slope (2 stations). The THg concentration in the surface sediment increased from the inner shelf (0.25 ± 0.023 nmol g-1) toward the slope (0.52 nmol g-1), and, when normalized to total organic carbon content, the THg showed a positive correlation with the clay-to-sand ratio (r2 = 0.48, p = 0.012) and degree of chemical weathering (r2 = 0.79, p = 0.0001). The highest MeHg concentrations (3.0 ± 1.8 pmol g-1), as well as peaks in the S/C ratio (0.012 ± 0.002) of sediment-leached organic matter, were found on the mid-shelf, suggesting that the activities of sulfate reducers control the net Hg(II) methylation rates in the sediment. This was supported by results from a principal component analysis (PCA) performed with Hg species concentrations and sediment-leached organic matter compositions. The site-specific variation in MeHg showed the highest similarity with that of CHONS compounds in the PCA, where Deltaproteobacteria were projected to be putative Hg(II) methylators in the gene analysis. In summary, the hydrodynamic sorting of lithogenic particles appears to govern the cross-shelf distribution of THg, and in situ methylation is considered a major source of MeHg in the ESS sediment.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Mercúrio/análise , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Compostos de Metilmercúrio/análise , Oceanos e Mares
3.
Mar Pollut Bull ; 200: 116035, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38271917

RESUMO

The supply and sources of N and Hg in the Geum estuary of the western coast of Korea were evaluated. Triple isotope proxies (δ15NNO3, Δ17ONO3 and δ18ONO3) of NO3- combined with conservative mixing between river and ocean waters were used to improve isotope finger-printing methods. The N pool in the Geum estuary was primarily influenced by the Yellow Sea water, followed by riverine discharge (821 × 106 mol yr-1) and atmospheric deposition (51 × 106 mol yr-1). The influence of the river was found to be greater for Hg than that of the atmosphere. The triple isotope proxies revealed that the riverine and atmospheric inputs of N have been affected by septic wastes and fossil fuel burning, respectively. From the inner estuary towards offshore region, the influence of the river diminishes, thus increasing the relative impact of the atmosphere. Moreover, the isotope proxies showed a significant influence of N assimilation in February and nitrification in May.


Assuntos
Mercúrio , Poluentes Químicos da Água , Isótopos de Nitrogênio/análise , Estuários , Ecossistema , Monitoramento Ambiental/métodos , Rios , Poluentes Químicos da Água/análise , Nitratos/análise
4.
Artigo em Inglês | MEDLINE | ID: mdl-37890996

RESUMO

BACKGROUND: Rosacea is a chronic skin disorder characterised by abnormal neurovasculature and inflammation in the central region of the face. The efficacy of pulsed-dye laser and intense pulsed light treatments for rosacea have been demonstrated in several clinical trials. However, there is currently no research on the efficacy of long-pulsed alexandrite laser (LPAL) therapy alone for rosacea-related facial redness and its effect on skin microbiota. AIM: To evaluate the efficacy of LPAL therapy on facial redness in rosacea and assess changes in skin microbiota composition. METHODS: Subjects with rosacea (n = 21, mean age: 39.2 ± 11.3 years) were recruited from two medical institutions and received monthly LPAL treatments (Clarity II™, Lutronic Corp.) for 3 months. At each visit, clinical photographs were taken, and erythema was measured using a spectrometer. At the initial and final visits, the Dermatology Life Quality Index (DLQI) and Skin Sensitivity Questionnaire (SSQ) were evaluated. Skin swabs were obtained at the initial and final visit, and facial microbiome composition was analysed using 16S rRNA amplicon sequencing. RESULTS: After three LPAL treatment sessions, the average facial erythema index, measured using Mexameter® decreased significantly from 360.0 ± 96.7 at baseline to 312.0 ± 94.5 at the final visit (p < .05). The DLQI and SSQ showed significant improvement of symptoms. Skin microbiome diversity and relative abundance were altered significantly, particularly in the genera Clostridium, Lawsonella, Bacteroides, and Lactobacillus. CONCLUSIONS: LPAL therapy alone showed favourable efficacy for the treatment of facial redness in rosacea, with some impacts on the skin microbiota composition.


Assuntos
Lasers de Estado Sólido , Rosácea , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Lasers de Estado Sólido/uso terapêutico , RNA Ribossômico 16S , Rosácea/radioterapia , Eritema , Resultado do Tratamento
5.
Adv Mater ; 36(8): e2309041, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38041566

RESUMO

Metal-organic frameworks (MOFs), which are highly ordered structures exhibiting sub-nanometer porosity, possess significant potential for diverse gas applications. However, their inherent insulative properties limit their utility in electrochemical gas sensing. This investigation successfully modifies the electrical conductivity of zeolitic imidazolte framework-8 (ZIF-8) employing a straightforward surface oxidation methodology. A ZIF-8 polycrystalline layer is applied on a wafer-scale oxide substrate and subjects to thermal annealing at 300 °C under ambient air conditions, resulting in nanoscale oxide layers while preserving the fundamental properties of the ZIF-8. Subsequent exposure to NO2 instigates the evolution of an electrically interconnected structure with the formation of electron-rich dopants derived from the decomposition of nitrogen-rich organic linkers. The N-carbon-hybridized ZnO/ZIF-8 device demonstrates remarkable sensitivity (≈130 ppm-1 ) and extreme selectivity in NO2 gas detection with a lower detection limit of 0.63 ppb under 150 °C operating temperature, surpassing the performance of existing sensing materials. The exceptional performances result from the Debye length scale dimensionality of ZnO and the high affinity of ZIF-8 to NO2 . The methodology for manipulating MOF conductivity through surface oxidation holds the potential to accelerate the development of MOF-hybridized conductive channels for a variety of electrical applications.

6.
Int J Dermatol ; 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38130023

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with various systemic and ocular complications. This study aimed to investigate the prevalence, risk factors, and clinical characteristics of ocular complications in a cohort of Korean AD patients. METHODS: A retrospective review of medical records was conducted for AD patients who visited the dermatology and ophthalmology clinics at the same institution. Demographic data, clinical characteristics, and types of ocular complications were recorded. Logistic regression analysis was performed to identify factors associated with ocular complications. RESULTS: A total of 212 AD patients were included in the study. The intraocular complications had a prevalence of 1.9%, whereas ocular surface diseases were observed more frequently, with prevalence of 13.2%. Among the ocular complications, blepharitis was the most prevalent, followed by atopic keratoconjunctivitis. Subcapsular cataract, atrophic hole, and retinal detachment were also observed. The head and neck score in the Eczema Area and Severity Index (EASI) emerged as a significant predictor for intraocular complications, independent of age, gender, total EASI score, and family history. No significant association was found between total EASI score and ocular surface disease. CONCLUSION: This study provides insights into the prevalence and risk factors of ocular complications in Korean AD patients. The head and neck score in EASI was identified as a significant predictor for intraocular complications. These findings emphasize the importance of comprehensive evaluation and interdisciplinary care for AD patients, particularly in identifying and managing potential vision-threatening complications.

7.
Light Sci Appl ; 12(1): 280, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37996413

RESUMO

Transition metal dichalcogenide (TMD) layered semiconductors possess immense potential in the design of photonic, electronic, optoelectronic, and sensor devices. However, the sub-bandgap light absorption of TMD in the range from near-infrared (NIR) to short-wavelength infrared (SWIR) is insufficient for applications beyond the bandgap limit. Herein, we report that the sub-bandgap photoresponse of MoS2/Au heterostructures can be robustly modulated by the electrode fabrication method employed. We observed up to 60% sub-bandgap absorption in the MoS2/Au heterostructure, which includes the hybridized interface, where the Au layer was applied via sputter deposition. The greatly enhanced absorption of sub-bandgap light is due to the planar cavity formed by MoS2 and Au; as such, the absorption spectrum can be tuned by altering the thickness of the MoS2 layer. Photocurrent in the SWIR wavelength range increases due to increased absorption, which means that broad wavelength detection from visible toward SWIR is possible. We also achieved rapid photoresponse (~150 µs) and high responsivity (17 mA W-1) at an excitation wavelength of 1550 nm. Our findings demonstrate a facile method for optical property modulation using metal electrode engineering and for realizing SWIR photodetection in wide-bandgap 2D materials.

8.
Exp Mol Med ; 55(12): 2576-2585, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38036734

RESUMO

Osteoarthritis (OA) is a degenerative joint disease. While it is classically characterized by articular cartilage destruction, OA affects all tissues in the joints and is thus also accompanied by local inflammation, subchondral bone changes, and persistent pain. However, our understanding of the underlying subchondral bone dynamics during OA progression is poor. Here, we demonstrate the contribution of immunoglobulin superfamily 11 (IgSF11) to OA subchondral bone remodeling by using a murine model. In particular, IgSF11 was quickly expressed by differentiating osteoclasts and upregulated in subchondral bone soon after destabilization-of-the-medial-meniscus (DMM)-induced OA. In mice, IgSF11 deficiency not only suppressed subchondral bone changes in OA but also blocked cartilage destruction. The IgSF11-expressing cells in OA subchondral bone were found to be involved in osteoclast maturation and bone resorption and colocalized with receptor-activator of nuclear-factor κ-B (RANK), the key osteoclast differentiation factor. Thus, our study shows that blocking early subchondral bone changes in OA can ameliorate articular cartilage destruction in OA.


Assuntos
Reabsorção Óssea , Cartilagem Articular , Osteoartrite , Animais , Camundongos , Osso e Ossos , Reabsorção Óssea/genética , Modelos Animais de Doenças , Osteoartrite/genética , Osteoartrite/complicações , Osteoclastos
9.
Yonsei Med J ; 64(12): 721-729, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37992744

RESUMO

PURPOSE: Fractional microneedle radiofrequency (FMR) systems are used to treat inflammatory acne and scarring. Nonetheless, few controlled studies have combined this treatment with the traditional ablative fractional laser (AFL). We aimed to assess the safety and efficacy of the combination of FMR and AFL versus AFL alone in treating acne and acne scars. MATERIALS AND METHODS: In this 20-week, randomized, split-face study, 23 Korean patients with facial acne and acne scars underwent FMR and AFL treatments. One half of each patient's face was randomly assigned to receive FMR+AFL, whereas the other half received AFL alone. Treatments were administered in three consecutive sessions at 4-week intervals. This study investigated the severity of inflammatory acne, acne scars, individual lesion counts, depressed scar volumes, as well as patient and physician satisfaction. In addition, five patients underwent skin biopsy, and sebum output was measured. RESULTS: The FMR+AFL treatment demonstrated superior efficacy compared to AFL alone in terms of inflammatory acne and acne scar grading, lesion counts, and subjective satisfaction. The side effects were minimal and well-tolerated in both groups. Immunohistochemical findings from skin biopsy samples revealed that the application of FMR+AFL could induce an inhibitory effect on sebum secretion at the molecular level. CONCLUSION: FMR combined with AFL is a well-tolerated and effective treatment modality for inflammatory acne and acne scarring.


Assuntos
Acne Vulgar , Cicatriz , Humanos , Acne Vulgar/terapia , Acne Vulgar/patologia , Cicatriz/terapia , Cicatriz/patologia , Lasers , Pele/patologia , Resultado do Tratamento
10.
Nat Commun ; 14(1): 6811, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884499

RESUMO

Machine learning approaches using satellite imagery are providing accessible ways to infer socioeconomic measures without visiting a region. However, many algorithms require integration of ground-truth data, while regional data are scarce or even absent in many countries. Here we present our human-machine collaborative model which predicts grid-level economic development using publicly available satellite imagery and lightweight subjective ranking annotation without any ground data. We applied the model to North Korea and produced fine-grained predictions of economic development for the nation where data is not readily available. Our model suggests substantial development in the country's capital and areas with state-led development projects in recent years. We showed the broad applicability of our model by examining five of the least developed countries in Asia, covering 400,000 grids. Our method can both yield highly granular economic information on hard-to-visit and low-resource regions and can potentially guide sustainable development programs.

11.
Biomedicines ; 11(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37893216

RESUMO

Osteoarthritis (OA) is the most common joint disease that causes local inflammation and pain, significantly reducing the quality of life and normal social activities of patients. Currently, there are no disease-modifying OA drugs (DMOADs) available, and treatment relies on pain relief agents or arthroplasty. To address this significant unmet medical need, we aimed to develop monoclonal antibodies that can block the osteoclast-associated receptor (OSCAR). Our recent study has revealed the importance of OSCAR in OA pathogenesis as a novel catabolic regulator that induces chondrocyte apoptosis and accelerates articular cartilage destruction. It was also shown that blocking OSCAR with a soluble OSCAR decoy receptor ameliorated OA in animal models. In this study, OSCAR-neutralizing monoclonal antibodies were isolated and optimized by phage display. These antibodies bind to and directly neutralize OSCAR, unlike the decoy receptor, which binds to the ubiquitously expressed collagen and may result in reduced efficacy or deleterious off-target effects. The DMOAD potential of the anti-OSCAR antibodies was assessed with in vitro cell-based assays and an in vivo OA model. The results demonstrated that the anti-OSCAR antibodies significantly reduced cartilage destruction and other OA signs, such as subchondral bone plate sclerosis and loss of hyaline cartilage. Hence, blocking OSCAR with a monoclonal antibody could be a promising treatment strategy for OA.

12.
Cell ; 186(22): 4851-4867.e20, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37848036

RESUMO

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.


Assuntos
Síndrome Pós-COVID-19 Aguda , Serotonina , Humanos , COVID-19/complicações , Progressão da Doença , Inflamação , Síndrome Pós-COVID-19 Aguda/sangue , Síndrome Pós-COVID-19 Aguda/patologia , Serotonina/sangue , Viroses
13.
Nanoscale Adv ; 5(20): 5613-5626, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37822896

RESUMO

Nitrogen-doped carbon dots (CDs) have attracted considerable attention across various research areas and applications due to their enhanced optical properties and photostability. However, the mechanism of nitrogen incorporation in CDs remains elusive, hampering the precise control over nitrogen-incorporated structures and the investigation of the effects of nitrogen on the electronic structure and optical properties of CDs. In this study, we employed a rational design approach, utilizing glucosamine and ethylene glycol as the carbon source and co-reagent, respectively, to synthesize N-doped CDs. Our synthesis strategy involved pinacol rearrangement and iminium ion cyclization reactions, enabling the reliable formation of N-doped CDs. Notably, the resulting CDs exhibited distinctive emissive states attributed to heteroatomic defect structures, including oxygenic and nitrogenic polycyclic aromatic hydrocarbons. To gain further insights into their energy levels and electronic transitions, we conducted comprehensive investigations, employing extended Hückel calculations and pump-probe spectroscopy. The synthesized CDs displayed great promise as bioimaging and photodynamic therapy agents, highlighting their potential for biomedical applications. Moreover, our study significantly contributes valuable insights into the rational design of N-doped CDs with controllable chemical and electronic structures, thereby paving the way for advancements in their diverse range of applications.

14.
J Cosmet Laser Ther ; : 1-6, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37839083

RESUMO

We compared the effectiveness and safety of the long-pulsed neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser alone and combined with a 755-nm alexandrite laser for treating palmoplantar warts. We divided patients into two groups to receive up to four monthly treatments with Nd:YAG alone (single-wavelength) or combined with the alexandrite laser (dual-wavelength). We assessed treatment responses (according to clearance rate), vascular/hyperkeratosis grades, and patient satisfaction and pain ratings. The differences in treatment response (p = .348), patient satisfaction (p = .560), and pain ratings (p = .728) between the groups were not significant. The single- and dual-wavelength treatment options were equally effective in treating recalcitrant palmoplantar warts.

15.
bioRxiv ; 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37662341

RESUMO

G protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often limited at the receptor, tissue, and cellular level. Antibodies have the potential to address these limitations but their properties as GPCR ligands remain poorly characterized. Here, using protein engineering, pharmacological assays, and structural studies, we develop maternally selective heavy chain-only antibody ("nanobody") antagonists against the angiotensin II type I receptor (AT1R) and uncover the unusual molecular basis of their receptor antagonism. We further show that our nanobodies can simultaneously bind to AT1R with specific small-molecule antagonists and demonstrate that ligand selectivity can be readily tuned. Our work illustrates that antibody fragments can exhibit rich and evolvable pharmacology, attesting to their potential as next-generation GPCR modulators.

16.
Int J Mol Sci ; 24(18)2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37762688

RESUMO

Keloid scars are fibro-proliferative conditions characterized by abnormal fibroblast proliferation and excessive extracellular matrix deposition. The mammalian target of the rapamycin (mTOR) pathway has emerged as a potential therapeutic target in keloid disease. Silibinin, a natural flavonoid isolated from the seeds and fruits of the milk thistle, is known to inhibit the mTOR signaling pathway in human cervical and hepatoma cancer cells. However, the mechanisms underlying this inhibitory effect are not fully understood. This in vitro study investigated the effects of silibinin on collagen expression in normal human dermal and keloid-derived fibroblasts. We evaluated the effects of silibinin on the expressions of collagen types I and III and assessed its effects on the suppression of the mTOR signaling pathway. Our findings confirmed elevated mTOR phosphorylation levels in keloid scars compared to normal tissue specimens. Silibinin treatment significantly reduced collagen I and III expressions in normal human dermal and keloid-derived fibroblasts. These effects were accompanied by the suppression of the mTOR signaling pathway. Our findings suggest the potential of silibinin as a promising therapeutic agent for preventing and treating keloid scars. Further studies are warranted to explore the clinical application of silibinin in scar management.


Assuntos
Queloide , Humanos , Animais , Silibina/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR , Colágeno , Colágeno Tipo I/genética , Mamíferos
17.
Int J Mol Sci ; 24(16)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37629159

RESUMO

Long-term treatments for inflammatory skin diseases like atopic dermatitis or eczema can cause adverse effects. Super Protein Multifunction (SPM) was investigated as a potential treatment for managing skin inflammation by monitoring the expression of pro-inflammatory cytokines induced using LPS and poly(I:C)/TNFα in HaCaT keratinocytes and Hs27 fibroblasts as measured via RT-PCR. SPM solution was also assessed for its effect on cytokine release, measured using ELISA, in a UVB-irradiated 3D human skin model. To evaluate the efficiency of SPM, 20 patients with mild eczematous skin were randomized to receive SPM or vehicle twice a day for three weeks in a double-blind controlled trial. In vitro studies showed SPM inhibited inflammation-induced IL-1ß, IL-6, IL-33, IL-1α, TSLP, and TNFα expression or release. In the clinical study, the SPM group showed significant improvements in the IGA, PA, and DLQI scores compared to the vehicle group. Neither group showed significant differences in VAS (pruritus). Histological analysis showed reduced stratum corneum thickness and inflammatory cell infiltration. The results suggest that SPM may reduce inflammation in individuals with chronic eczematous skin.


Assuntos
Eczema , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/genética , Pele , Inflamação , Prurido , Citocinas , Excipientes
18.
Diabetes Metab J ; 47(6): 826-836, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37614025

RESUMO

BACKGRUOUND: There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM). METHODS: This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics. RESULTS: Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without. CONCLUSION: We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hiperglicemia , Feminino , Humanos , Glicemia/metabolismo , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hemoglobinas Glicadas , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Estilo de Vida
19.
J Eur Acad Dermatol Venereol ; 37(12): 2589-2600, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37606610

RESUMO

BACKGROUND: Rosacea is a common chronic inflammatory skin condition that is often refractory to treatment, with frequent relapses. Alterations in the skin immunological response and Demodex mite infestation are the primary aetiologic factors targeted for treatment. Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a nociceptive cation channel that plays a role in cutaneous neurogenic pain and can be activated by various rosacea triggers. OBJECTIVES: We investigated the effects of TRPV1 modulation in rosacea, focussing on Demodex mite colonization and cutaneous neurogenic inflammation. METHODS: We examined mRNA expression levels according to Demodex population counts. An in vitro study using capsazepine as a TRPV1 antagonist was performed to assess the influence of TRPV1 in keratinocytes. A rosacea-like mouse model was generated by the injection of the 37-amino acid C-terminal cathelicidin peptide (LL37), and changes in the skin, dorsal root ganglion (DRG) and ears were examined. RESULTS: Increased Demodex mite population counts were associated with increased expression levels of TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), and these levels could be reduced by capsazepine treatment in keratinocytes. In an in vivo study, the downstream effects of TRPV1 activation were investigated in the skin, DRG and ears of the rosacea-like mouse model. CONCLUSIONS: The findings of this study are instrumental for understanding the underlying causes of rosacea and could potentially lead to the development of new treatments targeting the NGF-TrkA-TRPV1 pathway. The identification of this pathway as a therapeutic target could represent a major breakthrough for rosacea research, potentially resulting in more effective and targeted rosacea treatments. This study contributes to an improved understanding of rosacea pathophysiology, which may lead to the development of more effective treatments in the future.


Assuntos
Infestações por Ácaros , Ácaros , Rosácea , Animais , Camundongos , Inflamação Neurogênica/complicações , Fator de Crescimento Neural/metabolismo , Rosácea/tratamento farmacológico , Infestações por Ácaros/complicações , Canais de Cátion TRPV/genética
20.
Sci Rep ; 13(1): 13448, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596459

RESUMO

Evaluation of scar severity is crucial for determining proper treatment modalities; however, there is no gold standard for assessing scars. This study aimed to develop and evaluate an artificial intelligence model using images and clinical data to predict the severity of postoperative scars. Deep neural network models were trained and validated using images and clinical data from 1283 patients (main dataset: 1043; external dataset: 240) with post-thyroidectomy scars. Additionally, the performance of the model was tested against 16 dermatologists. In the internal test set, the area under the receiver operating characteristic curve (ROC-AUC) of the image-based model was 0.931 (95% confidence interval 0.910‒0.949), which increased to 0.938 (0.916‒0.955) when combined with clinical data. In the external test set, the ROC-AUC of the image-based and combined prediction models were 0.896 (0.874‒0.916) and 0.912 (0.892‒0.932), respectively. In addition, the performance of the tested algorithm with images from the internal test set was comparable with that of 16 dermatologists. This study revealed that a deep neural network model derived from image and clinical data could predict the severity of postoperative scars. The proposed model may be utilized in clinical practice for scar management, especially for determining severity and treatment initiation.


Assuntos
Inteligência Artificial , Cicatriz , Humanos , Cicatriz/diagnóstico por imagem , Redes Neurais de Computação , Algoritmos , Cognição
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