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1.
Cell ; 186(13): 2823-2838.e20, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37236193

RESUMO

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-ß2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care.


Assuntos
Sistema Nervoso Entérico , Doenças Inflamatórias Intestinais , Humanos , Glucocorticoides/farmacologia , Inflamação , Sistema Nervoso Entérico/fisiologia , Estresse Psicológico
2.
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 de COVID-19 Pós-Aguda , Serotonina , Humanos , COVID-19/complicações , Progressão da Doença , Inflamação , Síndrome de COVID-19 Pós-Aguda/sangue , Síndrome de COVID-19 Pós-Aguda/patologia , Serotonina/sangue , Viroses
3.
Nature ; 612(7941): 739-747, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36517598

RESUMO

Exercise exerts a wide range of beneficial effects for healthy physiology1. However, the mechanisms regulating an individual's motivation to engage in physical activity remain incompletely understood. An important factor stimulating the engagement in both competitive and recreational exercise is the motivating pleasure derived from prolonged physical activity, which is triggered by exercise-induced neurochemical changes in the brain. Here, we report on the discovery of a gut-brain connection in mice that enhances exercise performance by augmenting dopamine signalling during physical activity. We find that microbiome-dependent production of endocannabinoid metabolites in the gut stimulates the activity of TRPV1-expressing sensory neurons and thereby elevates dopamine levels in the ventral striatum during exercise. Stimulation of this pathway improves running performance, whereas microbiome depletion, peripheral endocannabinoid receptor inhibition, ablation of spinal afferent neurons or dopamine blockade abrogate exercise capacity. These findings indicate that the rewarding properties of exercise are influenced by gut-derived interoceptive circuits and provide a microbiome-dependent explanation for interindividual variability in exercise performance. Our study also suggests that interoceptomimetic molecules that stimulate the transmission of gut-derived signals to the brain may enhance the motivation for exercise.


Assuntos
Eixo Encéfalo-Intestino , Dopamina , Exercício Físico , Microbioma Gastrointestinal , Motivação , Corrida , Animais , Camundongos , Encéfalo/citologia , Encéfalo/metabolismo , Dopamina/metabolismo , Endocanabinoides/antagonistas & inibidores , Endocanabinoides/metabolismo , Células Receptoras Sensoriais/metabolismo , Eixo Encéfalo-Intestino/fisiologia , Microbioma Gastrointestinal/fisiologia , Exercício Físico/fisiologia , Exercício Físico/psicologia , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/psicologia , Modelos Animais , Humanos , Estriado Ventral/citologia , Estriado Ventral/metabolismo , Corrida/fisiologia , Corrida/psicologia , Recompensa , Individualidade
4.
Nature ; 605(7908): 160-165, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35477756

RESUMO

Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently needed1. Here we identify a metabolite signalling pathway that provides actionable insights towards this goal. We perform a dietary screen in autochthonous animal models of CRC and find that ketogenic diets exhibit a strong tumour-inhibitory effect. These properties of ketogenic diets are recapitulated by the ketone body ß-hydroxybutyrate (BHB), which reduces the proliferation of colonic crypt cells and potently suppresses intestinal tumour growth. We find that BHB acts through the surface receptor Hcar2 and induces the transcriptional regulator Hopx, thereby altering gene expression and inhibiting cell proliferation. Cancer organoid assays and single-cell RNA sequencing of biopsies from patients with CRC provide evidence that elevated BHB levels and active HOPX are associated with reduced intestinal epithelial proliferation in humans. This study thus identifies a BHB-triggered pathway regulating intestinal tumorigenesis and indicates that oral or systemic interventions with a single metabolite may complement current prevention and treatment strategies for CRC.


Assuntos
Neoplasias Colorretais , Transdução de Sinais , Ácido 3-Hidroxibutírico/metabolismo , Ácido 3-Hidroxibutírico/farmacologia , Animais , Proliferação de Células , Transformação Celular Neoplásica , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Humanos
5.
Nat Chem Biol ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744986

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 levels. 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 and uncover the unusual molecular basis of their receptor antagonism. We further show that our nanobodies can simultaneously bind to angiotensin II type I receptor 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.

6.
Nano Lett ; 24(36): 11163-11169, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39225119

RESUMO

Prolonging hot carrier cooling, a crucial factor in optoelectronic applications, including hot carrier photovoltaics, presents a significant challenge. High-energy band-nesting excitons within parallel bands offer a promising and underexplored avenue for addressing this issue. Here, we exploit an exceptional D exciton cooling prolongation of 2 to 3 orders of magnitude compared to sub-picosecond in typical transition metal dichalcogenides (TMDs) owing to the complex Coulomb environment and the sequential and mismatch-valley relaxation. Simultaneously, the intervalley scattering upconversion of band-edge excitons with the slow D exciton formation in the metastable Γ valley/hill also reduces the cooling rate. We successfully extract D and C excitons as hot carriers through integrating with various thicknesses of TiOx, achieving the highest efficiency of 98% and 85% at a Ti thickness of 2 nm. Our findings highlight the potential of band-nesting excitons for extending hot carrier cooling time, paving the way for advancements in hot carrier-based optoelectronic devices.

7.
J Am Chem Soc ; 146(21): 14724-14733, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38757532

RESUMO

Despite decades of research, the dominant charge generation mechanism in organic bulk heterojunction (BHJ) devices is not completely understood. While the local dielectric environments of the photoexcited molecules are important for exciton dissociation, conventional characterizations cannot separately measure the polarizability of electron-donor and electron-acceptor, respectively, in their blends, making it difficult to decipher the spectrally different charge generation efficiencies in organic BHJ devices. Here, by spectrally resolved electroabsorption spectroscopy, we report extraction of the excited state polarizability for individual donors and acceptors in a series of organic blend films. Regardless of the donor and acceptor, we discovered that larger exciton polarizability is linked to larger π-π coherence length and faster charge transfer across the heterojunction, which fundamentally explains the origin of the higher charge generation efficiency near 100% in the BHJ photodiodes. We also show that the molecular packing of the donor and acceptor influence each other, resulting in a synergetic enhancement in the exciton polarizability.

8.
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
9.
J Drugs Dermatol ; 23(5): 353-359, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709701

RESUMO

BACKGROUND: Medical aesthetic procedures for facial antiaging with laser and energy-based devices (EBDs) are rapidly increasing, but standards integrating skincare before, during, and after these treatments are lacking. The algorithm for integrated skin care for facial antiaging treatment with EBDs aims to stimulate healing, reduce downtime, and improve comfort and treatment outcomes. METHODS: A panel of 8 global physicians employed a modified Delphi method and reached a consensus on the algorithm integrating skincare based on the best available evidence, the panel's clinical experience, and opinions. RESULTS: The algorithm has a pretreatment (starts 2 - 4 weeks before the procedure) and treatment (day of treatment) section, followed by care after the procedure (0 - 7 days) and follow-up care (1 - 4 weeks after the procedure or ongoing). Applying a broad-spectrum sunscreen with an SPF 50 or higher, combined with protective measures such as wearing a wide-brimmed hat and sunglasses, is recommended to protect the face from sun exposure. Dyschromia is a significant concern for those with skin of color (SOC). Clinicians may recommend skincare using a gentle cleanser and moisturizer containing vitamins C and E, retinoid, or other ingredients such as niacinamide, kojic acid, licorice root extract, azelaic acid, and tranexamic acid, depending on the patient's facial skin condition. CONCLUSION: Medical aesthetic procedures for facial antiaging with EBDs integrating skincare or topical treatments may improve outcomes and patient satisfaction. Topical antioxidants and free radical quenchers can combat photodamage and may offer a safe alternative to topical hydroquinone.  J Drugs Dermatol. 2024;23(5):353-359.     doi:10.36849/JDD.8092.


Assuntos
Algoritmos , Satisfação do Paciente , Envelhecimento da Pele , Higiene da Pele , Humanos , Envelhecimento da Pele/efeitos dos fármacos , Higiene da Pele/métodos , Técnica Delphi , Resultado do Tratamento , Face , Terapia a Laser/métodos , Protetores Solares/administração & dosagem
10.
Ecotoxicol Environ Saf ; 286: 117131, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39405973

RESUMO

Due to their worldwide distribution and persistence, mercury (Hg), and nano- and microplastics (NMPs) pose major threats to global ocean ecosystems. Hg and NMPs co-exist in the ocean and can interact with each other. However, information on the toxicity of this interaction to marine biota remains limited. Thus, we investigated the toxicological interaction between HgCl2 (Hg) and NMPs by studying the influence of different sizes of polystyrene beads (0.05-, 0.5-, and 6-µm) on Hg accumulation in the brackish water flea Diaphanosoma celebensis. The Hg adsorption capacity of NPs (0.05-µm) was higher than that of MPs (0.5- and 6-µm). Only the group co-exposed to both Hg and NPs showed increased Hg content in D. celebensis. Multixenobiotic resistance (MXR) activity and transcriptional modulation of transporter genes (ABCBs and ABCCs) were decreased by NMP exposure, particularly by NPs, suggesting MXR disruption by NPs. However, only the activity of multidrug resistance-associated proteins (MRPs; ABCCs) increased with Hg exposure and decreased upon NP+Hg co-exposure, indicating an important role of ABCC in Hg efflux. Furthermore, in vivo toxicity tests showed a synergistic toxic interaction between Hg and NPs on the reproduction of D. celebensis. Our findings suggest that NPs have the potential to enhance the toxicity of Hg, increasing Hg accumulation not only by serving Hg as a carrier but also by disrupting MXR.

11.
Sensors (Basel) ; 24(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38931635

RESUMO

In this review, recent advances regarding the integration of machine learning into electrochemical analysis are overviewed, focusing on the strategies to increase the analytical context of electrochemical data for enhanced machine learning applications. While information-rich electrochemical data offer great potential for machine learning applications, limitations arise when sensors struggle to identify or quantitatively detect target substances in a complex matrix of non-target substances. Advanced machine learning techniques are crucial, but equally important is the development of methods to ensure that electrochemical systems can generate data with reasonable variations across different targets or the different concentrations of a single target. We discuss five strategies developed for building such electrochemical systems, employed in the steps of preparing sensing electrodes, recording signals, and analyzing data. In addition, we explore approaches for acquiring and augmenting the datasets used to train and validate machine learning models. Through these insights, we aim to inspire researchers to fully leverage the potential of machine learning in electroanalytical science.

12.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38892302

RESUMO

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity.


Assuntos
Apoptose , Mitocôndrias , NADPH Oxidase 4 , Neurônios , Material Particulado , Espécies Reativas de Oxigênio , Material Particulado/toxicidade , NADPH Oxidase 4/metabolismo , NADPH Oxidase 4/genética , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Linhagem Celular Tumoral , Estresse Oxidativo/efeitos dos fármacos , Animais , Camundongos , NADPH Oxidase 2/metabolismo , NADPH Oxidase 2/genética
13.
Korean J Physiol Pharmacol ; : 577, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39482235

RESUMO

Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored. This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki- 1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.

14.
Curr Issues Mol Biol ; 45(3): 2090-2104, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36975504

RESUMO

Crocin is a hydrophilic carotenoid pigment found in the stigma of Crocus sativus or the fruit of Gardenia jasminoides. In this study, we investigated the effects of Crocin on the activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) inflammasome in J774A.1 murine macrophage cells and monosodium urate (MSU)-induced peritonitis. Crocin significantly inhibited Nigericin-, adenosine triphosphate (ATP)-, MSU-induced interleukin (IL)-1ß secretion, and caspase-1 cleavage without affecting pro-IL-1ß and pro-caspase-1. Crocin also suppressed gasdermin-D cleavage and lactate dehydrogenase release and enhanced cell viability, indicating that Crocin reduces pyroptosis. Similar effects were observed in primary mouse macrophages. However, Crocin did not affect poly(dA:dT)-induced absent in melanoma 2 (AIM2) and muramyl dipeptide-induced NLRP1 inflammasomes. Crocin decreased Nigericin-induced oligimerization and the speck formation of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Crocin also dramatically alleviated the ATP-induced production of mitochondrial reactive oxygen species (mtROS). Finally, Crocin ameliorated the MSU-induced production of IL-1ß and IL-18 and the recruitment of neutrophils during peritoneal inflammation. These results suggest that Crocin suppresses NLRP3 inflammasome activation by blocking mtROS production and ameliorates MSU-induced mouse peritonitis. Thus, Crocin may have therapeutic potential in various NLRP3 inflammasome-related inflammatory diseases.

15.
Opt Express ; 31(10): 16205-16212, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37157704

RESUMO

We investigate the dynamics of surface plasmon (SP) lasing in Au gratings fabricated on InGaAs with a period of around 400 nm, which locates the SP resonance near the semiconductor energy gap and facilitates efficient energy transfer. By optically pumping the InGaAs to reach the population inversion required for the amplification and the lasing, we observe SP lasing at specific wavelengths that satisfy the SPR condition depending on the grating period. The carrier dynamics in semiconductor and the photon density in the SP cavity was investigated from the time-resolved pump-probe measurement and the time resolved photoluminescence spectroscopy, respectively. Our results reveal that the photon dynamics is strongly correlated with the carrier dynamics and the lasing build-up is accelerated as the initial gain proportional to the pumping power increases, and this trend is satisfactorily explained using the rate equation model.

16.
Mol Pharm ; 20(1): 267-278, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36542354

RESUMO

Early diagnosis of radiation-induced pulmonary fibrosis (RIPF) in lung cancer patients after radiation therapy is important. A gastrin-releasing peptide receptor (GRPR) mediates the inflammation and fibrosis after irradiation in mice lungs. Previously, our group synthesized a GRPR-targeted positron emission tomography (PET) imaging probe, [64Cu]Cu-NODAGA-galacto-bombesin (BBN), an analogue peptide of GRP. In this study, we evaluated the usefulness of [64Cu]Cu-NODAGA-galacto-BBN for the early prediction of RIPF. We prepared RIPF mice and acquired PET/CT images of [18F]F-FDG and [64Cu]Cu-NODAGA-galacto-BBN at 0, 2, 5, and 11 weeks after irradiation (n = 3-10). We confirmed that [64Cu]Cu-NODAGA-galacto-BBN targets GRPR in irradiated RAW 264.7 cells. In addition, we examined whether [64Cu]Cu-NODAGA-galacto-BBN monitors the therapeutic efficacy in RIPF mice (n = 4). As a result, the lung uptake ratio (irradiated-to-normal) of [64Cu]Cu-NODAGA-galacto-BBN was the highest at 2 weeks, followed by its decrease at 5 and 11 weeks after irradiation, which matched with the expression of GRPR and was more accurately predicted than [18F]F-FDG. These uptake results were also confirmed by the cell uptake assay. Furthermore, [64Cu]Cu-NODAGA-galacto-BBN could monitor the therapeutic efficacy of pirfenidone in RIPF mice. We conclude that [64Cu]Cu-NODAGA-galacto-BBN is a novel PET imaging probe for the early prediction of RIPF-targeting GRPR expressed during the inflammatory response.


Assuntos
Fibrose Pulmonar , Receptores da Bombesina , Animais , Camundongos , Receptores da Bombesina/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/etiologia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Bombesina/metabolismo , Pulmão/diagnóstico por imagem , Pulmão/metabolismo , Linhagem Celular Tumoral
17.
BMC Cardiovasc Disord ; 23(1): 186, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024773

RESUMO

BACKGROUND: Cardiac rehabilitation (CR) is an essential component in secondary prevention of cardiovascular diseases. Current guidelines recommend that the program should be comprehensive including multidisciplinary behavioral intervention, not only exercise training. While the utilization of CR is gradually increasing, the comprehensiveness of the program has not been systemically evaluated in Korea. METHODS: During the year 2020, nation-wide survey was done to evaluate the current status of CR in Korea. Survey was done by web-based structured questionnaire. Survey was requested to 164 hospitals performing percutaneous coronary intervention. RESULTS: Among 164 hospitals, 47 (28.7%) hospitals had CR programs. In hospitals with CR, multidisciplinary intervention other than exercise-based program was provided only partially: nutritional counseling (63%), vocational counseling for return to work (39%), stress management (31%), psychological evaluation (18%). Personnel for CR was commonly not dedicated to the program or even absent: (percentage of dedicated, concurrent with other work, absent) physical therapist (59, 41, 0%), nurse (31, 69, 0%), dietician (6, 65, 29%), clinical psychologist (0, 37, 63%). CONCLUSION: Comprehensiveness of CR in Korea is suboptimal and human resource for it is poorly disposed. More awareness of current status by both clinicians and health policy makers is needed and insurance reimbursement for educational program should be improved.


Assuntos
Reabilitação Cardíaca , Doenças Cardiovasculares , Cardiopatias , Humanos , Cardiopatias/reabilitação , Inquéritos e Questionários , República da Coreia/epidemiologia
18.
Dermatol Surg ; 49(7): 635-640, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37235875

RESUMO

BACKGROUND: Mohs micrographic surgery, involving pathology of the surgical margin, has the lowest recurrence rate for skin cancer. Moreover, because of technological advances, digital pathology systems are gradually being adopted in hospitals. Yongin Severance Hospital was the first hospital to construct a fully digitalized pathology system in Korea. OBJECTIVE: To evaluate the efficiency and characteristics of the digital pathology system for Mohs micrographic surgery. METHODS: The medical records of 80 patients with skin cancer who underwent Mohs micrographic surgery from March 2020 to August 2022 were analyzed for the number of frozen margins, number of stages, operation time, and recurrence rate to compare cases based on the pathology system. RESULTS: Overall, 23 and 57 patients were examined using the conventional and digital pathology systems, respectively. The mean number of final stages was 0.494 lower ( p -value = .008), the time from the previous to the next stage was 0.687-fold shorter ( p = .002), and the rate of switching from positive to negative margins was 1.990 times higher ( p = .044) in the digital than the conventional group. LIMITATIONS: Retrospective single-center experience; short follow-up time. CONCLUSION: Digital pathology reduces operative time and increases accuracy in Mohs micrographic surgery.


Assuntos
Cirurgia de Mohs , Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Margens de Excisão
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.
J Cosmet Laser Ther ; 25(5-8): 86-91, 2023 Nov 17.
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.


Assuntos
Berílio , Lasers de Estado Sólido , Verrugas , Humanos , Lasers de Estado Sólido/uso terapêutico , Verrugas/radioterapia , Satisfação do Paciente , Dor/etiologia , Resultado do Tratamento
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