RESUMO
Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis. E2F1 targets included glycolysis and metabolic genes including CKB that enabled cells to meet metabolic demands in challenging environments, as well as inflammatory cytokine-driven target genes. Expression quantitative trait locus analysis linked increased COMMD1 expression with decreased bone erosion in rheumatoid arthritis. Myeloid deletion of Commd1 resulted in increased osteoclastogenesis in arthritis and inflammatory osteolysis models. These results identify COMMD1 and an E2F-metabolic pathway as key regulators of osteoclastogenic responses under pathological inflammatory conditions and provide a mechanism by which hypoxia augments inflammation and bone destruction.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Artrite Reumatoide/imunologia , Macrófagos/imunologia , Osteogênese/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Células Cultivadas , Modelos Animais de Doenças , Fator de Transcrição E2F1/metabolismo , Feminino , Humanos , Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Transdução de SinaisRESUMO
In temperate mixed forests, dominant ectomycorrhizal (EM) tree species usually coexist with diverse arbuscular mycorrhizal (AM) understorey tree species. Here, we investigated the spatial associations between AM and EM trees in two > 20 ha temperate forest mega-plots to better understand the observed 'EM-dominant versus AM-diverse' coexistence. Overall, we found that positive spatial associations (e.g., facilitation) were mostly related to EM trees, while negative spatial associations (e.g., inhibition) were mainly related to AM trees. Because adult EM trees tended to facilitate surrounding AM and EM saplings and other EM adults in these two forests, facilitation hotspots that stabilize AM-EM tree coexistence should be centred around EM tree species rather than around AM tree species. Together, we propose a novel EM-stabilization mechanism, which emphasises how, despite some species-specific variation, EM tree species foster 'EM-dominant versus AM-diverse' coexistence in temperate mixed forests by facilitating other trees.
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Florestas , Micorrizas , Árvores , Micorrizas/fisiologia , Árvores/microbiologiaRESUMO
RATIONALE & OBJECTIVE: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Twenty adults with ADPKD (age, 31±6 years; 65% women; body mass index [BMI], 26.8 [22.7-30.4] kg/m2; estimated glomerular filtration rate [eGFR, 2021 CKD-EPI creatinine], 103±18mL/min/1.73m2; height-adjusted total kidney volume [HTKV], 731±370mL/m; Mayo classifications 1B [5%], 1C [42%], 1D [21%], and 1E [32%]) and 11 controls in normal weight category (NWC) (age, 25±3 years; 45% women; BMI, 22.5 [21.7-24.2] kg/m2; eGFR, 113±15mL/min/1.73m2; HTKV, 159±31mL/m) at the University of Colorado Anschutz Medical Campus. PREDICTORS: ADPKD status (yes/no) and severity (Mayo classifications). OUTCOME: HTKV and cyst burden by magnetic resonance imaging, kidney oxidative metabolism, and perfusion by 11C-acetate positron emission tomography/computed tomography, insulin sensitivity by hyperinsulinemic-euglycemic clamps (presented as ratio of M-value of steady state insulin concentration [M/I]). ANALYTICAL APPROACH: For categorical variables, χ2/Fisher's exact tests, and for continuous variables t tests/Mann-Whitney U tests. Pearson correlation was used to estimate the relationships between variables. RESULTS: Compared with NWC individuals, the participants with ADPKD exhibited lower mean±SD M/I ratio (0.586±0.205 vs 0.424±0.171 [mg/kg lean/min]/(µIU/mL), P=0.04), lower median cortical perfusion (1.93 [IQR, 1.80-2.09] vs 0.68 [IQR, 0.47-1.04] mL/min/g, P<0.001) and lower median total kidney oxidative metabolism (0.17 [IQR, 0.16-0.19] vs. 0.14 [IQR, 0.12-0.15] min-1, P=0.001) in voxel-wise models excluding cysts. HTKV correlated inversely with cortical perfusion (r: -0.83, P < 0.001), total kidney oxidative metabolism (r: -0.61, P<0.001) and M/I (r: -0.41, P = 0.03). LIMITATIONS: Small sample size and cross-sectional design. CONCLUSIONS: Adults with ADPKD and preserved kidney function exhibited impaired renal perfusion and kidney oxidative metabolism across a wide range of cysts and kidney enlargements. FUNDING: Grants from government (National Institutes of Health, Centers for Disease Control and Prevention) and not-for-profit (JDRF) entities. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study numbers NCT04407481 and NCT04074668. PLAIN-LANGUAGE SUMMARY: In our study, we explored how a common genetic kidney condition, autosomal dominant polycystic kidney disease (ADPKD), relates to kidney metabolism. ADPKD leads to the growth of numerous cysts in the kidneys, which can impact their ability to work properly. We wanted to understand the kidneys' ability to process oxygen and blood flow in ADPKD. Our approach involved using advanced imaging techniques to observe kidney metabolism and blood flow in people with ADPKD compared with healthy individuals. We discovered that those with ADPKD had significant changes in kidney oxygen metabolism even when their kidney function was still normal. These findings are crucial as they provide deeper insights into ADPKD, potentially guiding future treatments to target these changes.
Assuntos
Taxa de Filtração Glomerular , Rim , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/metabolismo , Rim Policístico Autossômico Dominante/patologia , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Feminino , Projetos Piloto , Masculino , Adulto , Estudos Transversais , Rim/patologia , Rim/diagnóstico por imagem , Rim/metabolismo , Adulto Jovem , Metabolismo Energético/fisiologia , Cistos/metabolismo , Cistos/patologia , Cistos/diagnóstico por imagemRESUMO
Lung-resident neutrophils need to be tightly regulated to avoid degranulation- and cytokine-associated damage to fragile alveolar structures that can lead to fatal outcomes. Here we show that lung neutrophils (LNs) express distinct surface proteins and genes that distinguish LNs from bone marrow and blood neutrophils. Functionally, LNs show impaired migratory activity toward chemoattractants and produce high levels of interleukin-6 (IL-6) at steady state and low levels of tumor necrosis factor-α in response to lipopolysaccharide (LPS) challenge. Treating bone marrow neutrophils with bronchoalveolar lavage fluid or prostaglandin E2 induces LN-associated characteristics, including the expression of transglutaminase 2 (Tgm2) and reduced production of inflammatory cytokines upon LPS challenge. Neutrophils from Tgm2-/- mice release high levels of inflammatory cytokines in response to LPS. Lung damage is significantly exacerbated in Tgm2-/- mice in an LPS-induced acute respiratory distress syndrome model. Collectively, we demonstrate that prostaglandin E2 is a key factor for the generation of LNs with unique immune suppressive characteristics, acting through protein kinase A and Tgm2, and LNs play essential roles in protection of the lungs against pathogenic inflammation.
Assuntos
Dinoprostona , Neutrófilos , Animais , Líquido da Lavagem Broncoalveolar/química , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Lipopolissacarídeos , Pulmão/patologia , Camundongos , Neutrófilos/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Live commensal Bacillus siamensis LF4 showed reparative potentials against high SM-induced negative effects, but whether its paraprobiotic (heat-killed B. siamensis, HKBS) and postbiotic (cell-free supernatant, CFS) forms had reparative functions and potential mechanisms are not yet known. In this study, the reparative functions of HKBS and CFS were investigated by establishing an injured model of spotted seabass (Lateolabrax maculatus) treated with dietary high soybean meal (SM). The results showed that HKBS and CFS effectively mitigated growth suppression, immune deficiency, and liver injury induced by dietary high SM. Simultaneously, HKBS and CFS application positively shaped intestinal microbiota by increased the abundance of beneficial bacteria (Fusobacteria, Firmicutes, Bacteroidota, and Cetobacterium) and decreased harmful bacteria (Proteobacteria and Plesiomonasare). Additionally, HKBS and CFS improved SM-induced intestinal injury by restoring intestinal morphology, upregulating the expression of tight junction proteins, anti-inflammatory cytokines, antimicrobial peptides, downregulating the expression of pro-inflammatory cytokines and apoptotic proteins. Furthermore, HKBS and CFS intervention significantly activated TLR2, TLR5 and MyD88 signaling, and eventually inhibited p38 and NF-κB pathways. In conclusion, paraprobiotic (HKBS) and postbiotic (CFS) from B. siamensis LF4 can improve growth, immunity, repair liver and intestinal injury, and shape intestinal microbiota in L. maculatus fed high soybean meal diet, and TLRs/p38 MAPK/NF-κB signal pathways might be involved in those processes. These results will serve as a base for future application of paraprobiotics and postbiotics to prevent and repair SM-induced adverse effects in fish aquaculture.
Assuntos
Bacillus , Bass , NF-kappa B , Animais , Farinha , Dieta , Fígado/metabolismo , Citocinas/metabolismo , Ração Animal/análiseRESUMO
An eight-week feeding trial was designed to assess which component of commensal Bacillus siamensis LF4 can mitigate SBM-induced enteritis and microbiota dysbiosis in spotted seabass (Lateolabrax maculatus) based on TLRs-MAPKs/NF-кB signaling pathways. Fish continuously fed low SBM (containing 16 % SBM) and high SBM (containing 40 % SBM) diets were used as positive (FM group) and negative (SBM group) control, respectively. After feeding high SBM diet for 28 days, fish were supplemented with B. siamensis LF4-derived whole cell wall (CW), cell wall protein (CWP), lipoteichoic acid (LTA) or peptidoglycan (PGN) until 56 days. The results showed that a high inclusion of SBM in the diet caused enteritis, characterized with significantly (P < 0.05) decreased muscular thickness, villus height, villus width, atrophied and loosely arranged microvillus. Moreover, high SBM inclusion induced an up-regulation of pro-inflammatory cytokines and a down-regulation of occludin, E-cadherin, anti-inflammatory cytokines, apoptosis related genes and antimicrobial peptides. However, dietary supplementation with CW, LTA, and PGN of B. siamensis LF4 could effectively alleviate enteritis caused by a high level of dietary SBM. Additionally, CWP and PGN administration increased beneficial Cetobacterium and decreased pathogenic Plesiomonas and Brevinema, while dietary LTA decreased Plesiomonas and Brevinema, suggesting that CWP, LTA and PGN positively modulated intestinal microbiota in spotted seabass. Furthermore, CW, LTA, and PGN application significantly stimulated TLR2, TLR5 and MyD88 expressions, and inhibited the downstream p38 and NF-κB signaling. Taken together, these results suggest that LTA and PGN from B. siamensis LF4 could alleviate soybean meal-induced enteritis and microbiota dysbiosis in L. maculatus, and p38 MAPK/NF-κB pathways might be involved in those processes.
Assuntos
Ração Animal , Bacillus , Dieta , Disbiose , Enterite , Doenças dos Peixes , Microbioma Gastrointestinal , Glycine max , Lipopolissacarídeos , Peptidoglicano , Ácidos Teicoicos , Animais , Doenças dos Peixes/imunologia , Ração Animal/análise , Enterite/veterinária , Enterite/imunologia , Enterite/microbiologia , Disbiose/veterinária , Disbiose/imunologia , Bacillus/fisiologia , Bacillus/química , Microbioma Gastrointestinal/efeitos dos fármacos , Dieta/veterinária , Glycine max/química , Lipopolissacarídeos/farmacologia , Ácidos Teicoicos/farmacologia , Peptidoglicano/farmacologia , Peptidoglicano/administração & dosagem , Bass/imunologia , Probióticos/farmacologia , Probióticos/administração & dosagem , Suplementos Nutricionais/análise , Distribuição AleatóriaRESUMO
Probiotic Bacillus pumilus SE5, heat-inactivated (HSE5) or active (ASE5), were supplemented to high soybean meal (HSM) (36 %) diet at whole term (0-56 days) and middle term (29-56 days) to investigate the preventing and repairing effects of B. pumilus SE5 in ameliorating the adverse effects of HSM in Epinephelus coioides. The results suggested that the HSM significantly decreased the weight gain rate (WGR), specific growth rate (SGR), and increased the feed conversion rate (FCR) at day 56 (P < 0.05), while HSE5 and ASE5 promoted the growth performance. The HSE5 and ASE5 showed preventive and reparative functions on the antioxidant capacity and serum immunity, with significantly increased the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) activities, and reduced malondialdehyde (MDA) level, and increased acid phosphatase (ACP), alkaline phosphatase (AKP), immunoglobulin M (IgM) and complement 3 (C3). The HSM impaired the intestinal health (destroyed the intestinal structure, significantly increased the contents of serum D-lactic acid and diamine oxidase, and reduced the expressions of claudin-3 and occludin), while HSE5 and ASE5 improved them at whole term and middle term. The HSM impaired the intestinal microbiota and reduced its diversity, and the HSE5 or ASE5 improved the intestinal microbiota (especially at whole term). HSE5 and ASE5 improved the intestinal mRNA expressions of anti-inflammatory genes (il-10 and tgf-ß1) and reduced the expressions of pro-inflammatory genes (il-1ß, il-8, il-12), and promoted the expressions of humoral immune factor-related genes (cd4, igm, mhcII-α) and antimicrobial peptide genes (ß-defensin, epinecidin-1 and hepcidin-1), and decreased the expressions of NF-κB/MAPK signaling pathway-related genes (ikk-α, nf-κb, erk-1), and improved the expressions of MAPK signaling pathway-related gene p38-α (P < 0.05). In conclusion, the heat-inactivated and active B. pumilus SE5 effectively prevented and repaired the suppressive effects of soybean meal in E. coioides, which underscored the potential of B. pumilus SE5 as a nutritional intervention agent in HSM diet in aquaculture.
Assuntos
Ração Animal , Bacillus pumilus , Bass , Dieta , Glycine max , Probióticos , Animais , Bass/imunologia , Ração Animal/análise , Dieta/veterinária , Probióticos/administração & dosagem , Probióticos/farmacologia , Bacillus pumilus/imunologia , Bacillus pumilus/química , Glycine max/química , Temperatura Alta/efeitos adversos , Imunidade Inata , Distribuição Aleatória , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
The epithelial-mesenchymal transition (EMT) and fibroblast activation are major events in idiopathic pulmonary fibrosis pathogenesis. Here, we investigated whether growth arrest-specific protein 6 (Gas6) plays a protective role in lung fibrosis via suppression of the EMT and fibroblast activation. rGas6 administration inhibited the EMT in isolated mouse ATII cells 14 days post-BLM treatment based on morphologic cellular alterations, changes in mRNA and protein expression profiles of EMT markers, and induction of EMT-activating transcription factors. BLM-induced increases in gene expression of fibroblast activation-related markers and the invasive capacity of primary lung fibroblasts in primary lung fibroblasts were reversed by rGas6 administration. Furthermore, the hydroxyproline content and collagen accumulation in interstitial areas with damaged alveolar structures in lung tissue were reduced by rGas6 administration. Targeting Gas6/Axl signaling events with specific inhibitors of Axl (BGB324), COX-2 (NS-398), EP1/EP2 receptor (AH-6809), or PGD2 DP2 receptor (BAY-u3405) reversed the inhibitory effects of rGas6 on EMT and fibroblast activation. Finally, we confirmed the antifibrotic effects of Gas6 using Gas6-/- mice. Therefore, Gas6/Axl signaling events play a potential role in inhibition of EMT process and fibroblast activation via COX-2-derived PGE2 and PGD2 production, ultimately preventing the development of pulmonary fibrosis.
Assuntos
Transição Epitelial-Mesenquimal , Fibroblastos , Peptídeos e Proteínas de Sinalização Intercelular , Animais , Camundongos , Ciclo-Oxigenase 2/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Pulmão/metabolismoRESUMO
Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), a conductive polymer, has gained popularity as the channel layer in organic electrochemical transistors (OECTs) due to its high conductivity and straightforward processing. However, difficulties arise in controlling its conductivity through gate voltage, presenting a challenge. To address this issue, aromatic amidine base, diazabicyclo[4.3.0]non-5-ene (DBN), is used to stabilize the doping state of the PEDOT chain through a reliable chemical de-doping process. Furthermore, the addition of the proton-penetrable material Nafion to the PEDOT:PSS channel layer induces phase separation between the substances. By utilizing a solution containing both PEDOT:PSS and Nafion as the channel layer of OECTs, the efficiency of ion movement into the channel from the electrolyte is enhanced, resulting in improved OECT performance. The inclusion of Nafion in the OECTs' channel layer modifies ion movement dynamics, allowing for the adjustment of synaptic properties such as pulse-paired facilitation, memory level, short-term plasticity, and long-term plasticity. This research aims to introduce new possibilities in the field of neuromorphic computing and contribute to biomimetic technology through the enhancement of electronic component performance.
Assuntos
Polímeros de Fluorcarboneto , Poliestirenos , Prótons , Poliestirenos/química , Polímeros de Fluorcarboneto/química , Polímeros/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Técnicas EletroquímicasRESUMO
S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.
Assuntos
Adipócitos/enzimologia , Adipogenia , Tecido Adiposo/enzimologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histonas/metabolismo , Obesidade/enzimologia , Processamento de Proteína Pós-Traducional , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Tecido Adiposo/patologia , Adiposidade , Animais , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Modelos Animais de Doenças , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Epigênese Genética , Células HeLa , Histonas/genética , Humanos , Masculino , Metilação , Camundongos , Obesidade/genética , Obesidade/patologia , PPAR gama/genética , PPAR gama/metabolismo , Fosforilação , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Transcrição Gênica , Transfecção , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Via de Sinalização WntRESUMO
Lingbao Huxin Dan (LBHX) is an effective prescription for treating various cardiovascular diseases. However, its systematic chemical composition analysis and important marker components remain unclear, which hinders the development of standards or guidelines for quality evaluation. Herein, a high-resolution and efficient method was established to comprehensively investigate the chemical ingredients and metabolites of LBHX by using gas chromatography-tandem mass spectrometry and ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. AutoDock Vina was applied to conduct visual screening for identifying potential active compounds targeting two important sick sinus syndrome-associated proteins. As a result, 53 volatile compounds, as well as 191 non-volatile chemical components, including bufadienolides, diterpenoids, bile acids, phenolic acids, and triterpenoid saponins, were unambiguously characterized or tentatively identified. Fifty prototypes and 62 metabolites were identified in the plasma of rats, whilst metabolism reactions included phase I reactions (hydrolysis, oxidation, and hydroxylation) and phase II reactions (glucuronidation and methylation). Eleven compounds with good binding affinity have been observed by docking with key proteins. It is the first systematic study on the pharmacodynamic material basis of LBHX and the result consolidates the foundation for further study regarding the mechanism in treating cardiovascular diseases.
Assuntos
Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Ratos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Ratos Sprague-Dawley , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas em Tandem/métodos , Medicamentos de Ervas Chinesas/análiseRESUMO
Similar to adults with posttraumatic stress disorder, children with early life adversity show bias in memory for negative emotional stimuli. However, it is not well understood how childhood adversity impacts mechanisms underlying emotional memory. N = 56 children (8-14 years, 48% female) reported on adverse experiences including potentially traumatic events and underwent fMRI while attending to emotionally pleasant, neutral, or negative images. Post-scan, participants completed a cued recall test to assess memory for these images. Emotional difference-in-memory (DM) scores were computed by subtracting negative or positive from neutral recall performance. All children showed enhancing effects of emotion on recall, with no effect of trauma load. However, children with less trauma showed a larger emotional DM for both positive and negative stimuli when amygdala or anterior hippocampal activity was higher. In contrast, highly trauma-exposed children demonstrated a lower emotional DM with greater amygdala or hippocampal activity. This suggested that alternative neural mechanisms might support emotional enhancement of encoding in children with greater trauma load. Whole-brain analyses revealed that right fusiform activity during encoding positively correlated with both trauma load and successful later recall of positive images. Therefore, highly trauma-exposed children may use alternative, potentially adaptive neural pathways via the ventral visual stream to encode positive emotional events.
RESUMO
BACKGROUND: A laser-induced needle-free microjet injector was developed for rapid, high-speed drug delivery of microliters into the skin. OBJECTIVE: This study evaluated the clinical rejuvenation effect of repeated dermal injections of the collagen simulator poly- dl -lactic acid (PDLA) using a laser-induced needle-free microjet injector. METHODS: Five PDLA injection sessions using a laser-induced needle-free microjet injector were conducted in patients concerned about aging skin. Facial uplifting, darkness, redness, roughness, pore size, subjective satisfaction, and side effects were evaluated before each session and 4 weeks after treatment completion. Histological evaluation was also performed with immunohistochemical staining of collagen and elastic fibers. RESULTS: The clinical results of 27 female patients were evaluated. The treatment resulted in a noticeable skin surface uplifting (0.711 ± 0.42 mm) and significant improvements in darkness ( p = .013), redness ( p = .009), and roughness ( p = .036), with no significant difference in the pore size ( p = .770). Patients were reported being satisfied with the overall therapeutic effects, despite mild and tolerable adverse effects. Histological findings revealed growth and thickening of collagen and elastic fibers, with marked increase in collagen I and III levels. CONCLUSION: Repeated dermal injections of PDLA using a laser-induced microjet injector offer excellent drug delivery, achieving high efficacy in skin rejuvenation, patient satisfaction, and safety.
Assuntos
Técnicas Cosméticas , Satisfação do Paciente , Poliésteres , Rejuvenescimento , Envelhecimento da Pele , Humanos , Feminino , Envelhecimento da Pele/efeitos dos fármacos , Poliésteres/administração & dosagem , Pessoa de Meia-Idade , Técnicas Cosméticas/instrumentação , Adulto , Face , Idoso , Polímeros/administração & dosagem , Injeções Intradérmicas/instrumentação , Ácido Láctico/administração & dosagem , Lasers , Preenchedores Dérmicos/administração & dosagemRESUMO
BACKGROUND: Common hyperkeratotic palmar skin lesions include chronic hand eczema (CHE), hyperkeratotic hand eczema (HHE), palmar psoriasis (PP). However, clinically differentiating these disorders is often challenging. OBJECTIVES: To compare the expressions of keratin (K) 5, K9, K14 and involucrin in palmar hyperkeratotic lesions (HHE, CHE and PP). MATERIALS AND METHODS: Immunohistochemical staining was performed on skin biopsy specimens obtained from the palms of patients clinically diagnosed with CHE, HHE and PP (n = 21, 24 and 18, respectively). RESULTS: K5 and K14 expression levels were higher in the spinous and granular layers of PP and HHE compared to CHE. Involucrin was expressed in the basal layer of PP and HHE but not in CHE. K9 expression was decreased in PP and HHE compared to CHE. CONCLUSION: Keratin and involucrin expression in the epidermis are markers of keratinocyte differentiation. Expression levels of keratin and involucrin were similar between the HHE and PP groups, suggesting that HHE shares pathogenesis with PP rather than CHE.
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Dermatite Alérgica de Contato , Eczema , Precursores de Proteínas , Psoríase , Dermatopatias , Humanos , Queratinas/metabolismoRESUMO
We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues (3Asp, 25Lys, and 34Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3Glu, 25Arg, and 34Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts.
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Peptídeos , Bloqueadores dos Canais de Potássio , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Cifozoários , Animais , Humanos , Bloqueadores dos Canais de Potássio/farmacologia , Bloqueadores dos Canais de Potássio/química , Canais de Potássio de Abertura Dependente da Tensão da Membrana/antagonistas & inibidores , Peptídeos/farmacologia , Peptídeos/química , Sequência de Aminoácidos , Venenos de Cnidários/farmacologia , Venenos de Cnidários/química , Alinhamento de SequênciaRESUMO
Enteromyxum leei and Enteromyxum fugu, which are myxosporean parasites, were first found in cultured tiger puffer Takifugu rubripes in Korea. We collected four tiger puffers that showed severe emaciation signs for our experiments. DNA sequencing was confirmed that the tiger puffers were coinfected with E. leei and E. fugu. Furthermore, similar amounts of E. leei and E. fugu were confirmed using real-time PCR in the intestine. To the best of our knowledge, there have been no reports of E. fugu infection in the olive flounder Paralichthys olivaceus. However, the diagnosis of inflowing water, discharged water and olive flounder samples using highly sensitive diagnostic methods confirmed the presence of E. fugu in water and fish samples from olive flounder farms near the tiger puffer farm. Therefore, the present study aimed to develop highly sensitive diagnostic methods such as real-time and two-step PCR for early diagnosis and follow-up of the emaciation disease and multiplex PCR for rapid diagnosis. The multiplex PCR method exhibited the same sensitivity as the one-step PCR method developed in this study, demonstrating its efficacy for rapid diagnosis. Therefore, the suggested methods can be utilized for the early diagnosis and rapid diagnosis of emaciation diseases and reduction of economic losses through rapid disease control.
Assuntos
Doenças dos Peixes , Linguado , Myxozoa , Animais , Takifugu , Emaciação , Doenças dos Peixes/diagnóstico , Doenças dos Peixes/parasitologia , Linguado/parasitologia , Myxozoa/genética , República da Coreia , ÁguaRESUMO
BACKGROUND: Medical students perceive the transition to clerkship education as stressful and challenging and view themselves as novices during their rotation in clerkship education. The developmental perspective is thus important because the transition to clerkship supports rather than hinders growth. Accordingly, this study examines medical students' transition to clerkship and their developmental features. METHODS: In-depth interviews were conducted with 18 medical students or graduates who had completed clerkships as medical students. Based on Straussian grounded theory, the collected data were analyzed in terms of the differences between pre- and post-clerkship education. RESULTS: Our data analysis revealed five stages of the transition process: "anticipation and anxiety," "reality check," "seeking solutions," "practical application," and "transition and stability." The core category, that is, "growing up from being students to being student doctors," was driven by patients who perceived the participants as student doctors. Meanwhile, the participants recognized that having a solution that is agreed upon by colleagues was more important than knowing the correct answer. The participants undergoing the transition to clerkship showed developmental features divided into three categories: personal, social, and professional. Specifically, they attempted to balance clerkship and life through personal development, learned to navigate around the hospital and reduced tension through social development, and developed clinical competencies focused on efficiency through professional development. CONCLUSIONS: This study explores the process of students' transition to clerkship education and the developmental features that emerge during this period. The students were motivated by patients who perceived them as student doctors. Through the transition, they maintained a work-life balance and adapted to hospitals but developed an overly doctor-centered attitude by cultivating clinical competencies with a focus on efficiency. To develop them into medical professionals, it is essential to assist their transition and cultivate a patient-centered attitude.
Assuntos
Estágio Clínico , Teoria Fundamentada , Pesquisa Qualitativa , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Feminino , Masculino , Adulto , Entrevistas como Assunto , Adulto Jovem , Competência ClínicaRESUMO
BACKGROUND: To improve the medical professionalism of medical students, it is essential to understand the dilemmas they face in various situations. This study explored the types and distribution of dilemmas Korean medical students encounter during their clinical clerkships. It then compared these with previous dilemma frameworks and identified the types and distribution of "complexity dilemmas," wherein two dilemma themes emerge in a single clinical situation. METHODS: The researchers organized and recorded a group discussion with 106 third-year medical students who had completed their clinical clerkships. These students participated in the discussion as part of an assignment, focusing on the dilemmas they encountered during their clerkships. For data analysis and visualization, the researchers employed the MAXQDA software program and utilized the template analysis method, a qualitative research methodology. RESULTS: A total of seven dilemma themes and sixteen sub-themes were identified. The identity-related dilemma concerning student-doctors had the highest frequency. The themes "mismatch" and "Nun-chi" emerged as new additions not found in previous dilemma frameworks. The complexity dilemmas appeared in the sequence of "identity-dignity," "identity-abuse," and "identity-consent". CONCLUSIONS: To navigate the unique dilemmas present within South Korea's clinical culture, several key issues need consideration: elevating the role of student-doctors, balancing the primary emphasis of educational hospitals on delivering medical services, and understanding interpersonal strategies, such as "Nun-chi".
Assuntos
Estágio Clínico , Estudantes de Medicina , Humanos , Profissionalismo , República da CoreiaRESUMO
BACKGROUND: Knowledge regarding differences in the order of frequency of complications after reverse total shoulder arthroplasty (RTSA) between Asian and Western populations is limited. We therefore asked for (1) What is the order of frequency of complications after primary RTSA in the Korean population? (2) What are the rates of complication, reoperation, and revision, and clinical outcomes after index surgery? METHODS: We retrospectively reviewed the 299 consecutive cases who underwent primary RTSA with more than 1 year of follow-up over a period of 12 years. The mean age of the patients was 73.4 years (range, 58-88 years) and the mean follow-up period was 3.8 years (range, 1-11.5 years). Evaluation of the clinical outcomes, complications, and reinterventions was performed at the final follow-up. RESULTS: The mean VAS pain score, UCLA score, ASES score, and SSV improved from 6.7, 10.2, 30.7, and 27.7% before RTSA to 1.4, 26.4, 80.5, 77.2% after RTSA, respectively (P < .001). Overall, 45 complications (15.1%) were observed in 44 patients. The order of frequency of complications was as follows: 16 cases of scapular stress fracture (5.4%), 9 intraoperative or postoperative periprosthetic fracture (3.0%), 6 brachial plexus injury (2.0%), 4 instability (1.3%), 2 glenoid loosening (0.7%), 2 glenoid disassembly (0.7%), 2 periprosthetic joint infection (0.7%), 1 glenoid fixation failure (0.3%), 1 humeral stem fixation failure (0.3%), 1 hematoma (0.3%), and 1 complex regional pain syndrome (0.3%). Reintervention was performed in 15 cases (5.0%) including reoperation (8 cases; 2.7%) and revision surgery (7 cases; 2.3%). CONCLUSION: At a mean follow-up period of 3.8 years, primary RTSA showed satisfactory clinical outcomes with a complication rate of 15.1%, a reoperation rate of 2.7%, and a revision rate of 2.3%. Scapular stress fracture appears to be the most common complication after RTSA in the Korean population.