RESUMO
Natural diamonds were (and are) formed (thousands of million years ago) in the upper mantle of Earth in metallic melts at temperatures of 900-1,400 °C and at pressures of 5-6 GPa (refs. 1,2). Diamond is thermodynamically stable under high-pressure and high-temperature conditions as per the phase diagram of carbon3. Scientists at General Electric invented and used a high-pressure and high-temperature apparatus in 1955 to synthesize diamonds by using molten iron sulfide at about 7 GPa and 1,600 °C (refs. 4-6). There is an existing model that diamond can be grown using liquid metals only at both high pressure and high temperature7. Here we describe the growth of diamond crystals and polycrystalline diamond films with no seed particles using liquid metal but at 1 atm pressure and at 1,025 °C, breaking this pattern. Diamond grew in the subsurface of liquid metal composed of gallium, iron, nickel and silicon, by catalytic activation of methane and diffusion of carbon atoms into and within the subsurface regions. We found that the supersaturation of carbon in the liquid metal subsurface leads to the nucleation and growth of diamonds, with Si playing an important part in stabilizing tetravalently bonded carbon clusters that play a part in nucleation. Growth of (metastable) diamond in liquid metal at moderate temperature and 1 atm pressure opens many possibilities for further basic science studies and for the scaling of this type of growth.
RESUMO
In this study, it is analyzed how sample geometry (spheres, nanofibers, or films) influences the graphitization behavior of polyacrylonitrile (PAN) molecules. The chemical bonding and changes in the composition of these three geometries are studied at the oxidation, carbonization, and graphitization stages via scanning electron microscopy (SEM), in situ thermogravimetric-infrared (TGA-IR) analysis, elemental analysis, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The influence of molecular alignment on the graphitization of the three sample geometries is investigated using synchrotron wide-angle X-ray diffraction (WAXD) and transmission electron microscopy (TEM). The effects of molecular alignment at different draw rates during spinning are explored in detail.
RESUMO
This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C ). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC.
Assuntos
Adenocarcinoma , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/mortalidade , Estudos Retrospectivos , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Adenocarcinoma/cirurgia , Adenocarcinoma/mortalidade , Fatores de Risco , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Adulto , Idoso , Papillomaviridae/isolamento & purificação , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Estadiamento de Neoplasias , Intervalo Livre de Doença , Papillomavirus HumanoRESUMO
BACKGROUND: Angiosarcoma is an extremely rare malignant tumor. So far, only about 42 cases of angiosarcoma involving the eyelids have been reported. Eyelid angiosarcoma occurs more frequently in elderly Caucasian males and is prone to misdiagnosis. We present a case report in a young Asian male patient with eyelid angiosarcoma that was misdiagnosed as a chalazion. CASE PRESENTATION: A 46-year-old South Korean male with no underlying disease had a right lower lid mass. The lesion was initially misdiagnosed as a chalazion at a local clinic, but a diagnosis of eyelid angiosarcoma was made after the first biopsy trial. PET-CT was performed to ensure that there was no metastasis in the whole body. Surgical excision with enough surgical margin was used alone for treatment and reconstruction was performed with a tarsoconjunctival advancement flap (modified Hughes procedure), which helped ensure good cosmesis. No recurrence was observed 4 years and 5 months after the surgery. CONCLUSIONS: The current study presents the first case of chalazion-mimicked eyelid angiosarcoma in a young Asian male aged under 50 years. This case shows that even if a benign eyelid disease is suspected in a young patient, an incisional biopsy must be performed to confirm whether the lesion is malignant. Since the prognosis is good for the case of eyelid angiosarcoma, if there is no clear evidence of distal metastasis, surgical resection should be performed with an enough safety margin.
Assuntos
Calázio , Neoplasias Palpebrais , Hemangiossarcoma , Idoso , Masculino , Humanos , Pessoa de Meia-Idade , Calázio/diagnóstico , Neoplasias Palpebrais/diagnóstico , Neoplasias Palpebrais/cirurgia , Neoplasias Palpebrais/patologia , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/cirurgia , Hemangiossarcoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Pálpebras/cirurgia , Pálpebras/patologiaRESUMO
Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.
Assuntos
Leonurus , Doenças Respiratórias , Camundongos , Animais , Leonurus/metabolismo , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Emissões de Veículos , Material Particulado , InflamaçãoRESUMO
Trunk compensatory movements frequently manifest during robotic-assisted arm reaching exercises for upper limb rehabilitation following a stroke, potentially impeding functional recovery. These aberrant movements are prevalent among stroke survivors and can hinder their progress in rehabilitation, making it crucial to address this issue. This study evaluated the efficacy of visual feedback, facilitated by an RGB-D camera, in reducing trunk compensation. In total, 17 able-bodied individuals and 18 stroke survivors performed reaching tasks under unrestricted trunk conditions and visual feedback conditions. In the visual feedback modalities, the target position was synchronized with trunk movement at ratios where the target moved at the same speed, double, and triple the trunk's motion speed, providing real-time feedback to the participants. Notably, trunk compensatory movements were significantly diminished when the target moved at the same speed and double the trunk's motion speed. Furthermore, these conditions exhibited an increase in the task completion time and perceived exertion among stroke survivors. This outcome suggests that visual feedback effectively heightened the task difficulty, thereby discouraging unnecessary trunk motion. The findings underscore the pivotal role of customized visual feedback in correcting aberrant upper limb movements among stroke survivors, potentially contributing to the advancement of robotic-assisted rehabilitation strategies. These insights advocate for the integration of visual feedback into rehabilitation exercises, highlighting its potential to foster more effective recovery pathways for post-stroke individuals by minimizing undesired compensatory motions.
Assuntos
Braço , Retroalimentação Sensorial , Movimento , Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Masculino , Retroalimentação Sensorial/fisiologia , Robótica/métodos , Feminino , Pessoa de Meia-Idade , Braço/fisiopatologia , Braço/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Movimento/fisiologia , Adulto , Terapia por Exercício/métodos , Tronco/fisiopatologia , Tronco/fisiologia , Idoso , Sobreviventes , Extremidade Superior/fisiopatologiaRESUMO
OBJECTIVE: Low-density lipoprotein cholesterol (LDL-C) has been commonly calculated by equations, but their performance has not been entirely satisfactory. This study aimed to develop a more accurate LDL-C prediction model using machine learning methods. METHODS: The study involved predicting directly measured LDL-C, using individual characteristics, lipid profiles, and other laboratory results as predictors. The models applied to predict LDL-C values were multiple regression, penalized regression, random forest, and XGBoost. Additionally, a novel 2-step prediction model was developed and introduced. The machine learning methods were evaluated against the Friedewald, Martin, and Sampson equations. RESULTS: The Friedewald, Martin, and Sampson equations had root mean squared error (RMSE) values of 12.112, 8.084, and 8.492, respectively, whereas the 2-step prediction model showed the highest accuracy, with an RMSE of 7.015. The LDL-C levels were also classified as a categorical variable according to the diagnostic criteria of the dyslipidemia treatment guideline, and concordance rates were calculated between the predictive values obtained from each method and the directly measured ones. The 2-step prediction model had the highest concordance rate (85.1%). CONCLUSION: The machine learning method can calculate LDL-C more accurately than existing equations. The proposed 2-step prediction model, in particular, outperformed the other machine learning methods.
Assuntos
LDL-Colesterol , Aprendizado de Máquina , Humanos , LDL-Colesterol/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , IdosoRESUMO
Selaginella tamariscina is a perennial plant that is used for diverse diseases. This study investigated whether Selaginella tamariscina has an antiviral effect against influenza A virus (IAV) infection. We used green fluorescent protein (GFP)-tagged influenza A virus (IAV) to examine the effect of Selaginella tamariscina ethanol extract (STE) on influenza viral infection. Fluorescence microscopy and flow cytometry showed that STE potently represses GFP expression by the virus, dose-dependently. STE significantly inhibited the expression of the IAV M2, NP, HA, NA, NS1, and PB2 proteins. Time-of-addition and hemagglutination inhibition assays showed that STE has an inhibitory effect on hemagglutinin and viral binding on the cells at an early infection time. In addition, STE exerted a suppressive effect on the neuraminidase activity of the H1N1 and H3N2 IAVs. Furthermore, dose-dependently, STE inhibited the cytopathic effect induced by H3N2, as well as by H1N1 IAV. Especially in the presence of 200 µg/mL STE, the cytopathic effect was completely blocked. Our findings suggest that STE has antiviral efficacy against IAV infection; thus, it could be developed as a natural IAV inhibitor.
Assuntos
Antivirais , Etanol , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Neuraminidase , Extratos Vegetais , Selaginellaceae , Neuraminidase/antagonistas & inibidores , Neuraminidase/metabolismo , Extratos Vegetais/farmacologia , Antivirais/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Humanos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Animais , Células Madin Darby de Rim Canino , Selaginellaceae/química , Cães , Vírus da Influenza A/efeitos dos fármacos , Hemaglutininas/metabolismo , Influenza Humana/tratamento farmacológicoRESUMO
BACKGROUND: The modified Nutrition Risk in the Critically Ill (mNUTRIC) score was developed to identify patients most likely to benefit from nutritional therapies and to stratify or select subjects for clinical trials. However, the validity of the score and the association between that score and the prognosis of patients in surgical intensive care units (SICUs) remain unclear. This study explored whether the score was a useful prognostic indicator for SICU patients, and whether survival could be improved via nutritional interventions based on mNUTRIC status. METHODS: This retrospective observational study enrolled 123 patients admitted to our SICU for critical care from January 2018 to December 2019. Among these, mNUTRIC medical data were available for 116. In-hospital mortality rates were compared based on both mNUTRIC status and the adequacy of nutritional supplementation. RESULTS: mNUTRIC-high status (5 points or more) was apparent in 16 â% of all critically ill surgical patients. In-hospital mortality was significantly higher in those with mNUTRIC-high scores (42.1 â% vs. 15.5 â%, P â= â0.023). Both groups exhibited less mortality when nutrition was adequate vs. inadequate (5.0 â% vs. 40.9 â% and 26.7 â% vs. 100 â%, respectively). In multivariate analysis, mNUTRIC-high scores and inadequate nutritional support were significant risk factors for in-hospital mortality (hazard ratios 7.336 and 13.636, P â= â0.027 and 0.002, respectively). CONCLUSION: In critically ill surgical patients, those identified as nutritionally high-risk using the mNUTRIC classification had poor in-hospital survival. Moreover, patients who received adequate nutritional support had a better prognosis than those who did not.
Assuntos
Estado Terminal , Mortalidade Hospitalar , Apoio Nutricional , Humanos , Estado Terminal/mortalidade , Estado Terminal/terapia , Masculino , Feminino , Estudos Retrospectivos , Prognóstico , Apoio Nutricional/métodos , Pessoa de Meia-Idade , Idoso , Avaliação Nutricional , Estado Nutricional , Medição de Risco/métodos , Unidades de Terapia Intensiva/estatística & dados numéricosRESUMO
Lespedeza maximowiczii (LM), a member of the legume family, has tyrosinase inhibitory and estrogenic activities. However, its effects on skin-related biological activities remain unclear. Therefore, the present study aimed to explore the effects of LM flower absolute (LMFAb) on skin-related biological events, especially skin re-epithelization, barrier and moisturizing-related keratinocyte (HaCaT cell) responses. In this study, LMFAb was isolated from LM flowers via solvent extraction and its chemical composition analysis was performed using gas chromatography/mass spectrometry. 5-bromo-2'-deoxyuridine incorporation, Boyden chamber, sprout outgrowth, enzyme-linked immunosorbent, and Western blot assay were used to analyze the biological effects of LMFAb on HaCaT cells (a human epidermal keratinocyte cell line). Twelve components were identified in LMFAb. LMFAb promoted cell proliferation, migration, and sprout outgrowth in HaCaT cells. The absolute enhanced the activations of MAPKs (ERK1/2, JNK, and p38), PI3K and AKT proteins in HaCaT cells and elevated collagen type I and IV levels in HaCaT cell conditioned medium. In addition, LMFAb induced an increase in the expression levels of epidermal barrier proteins (filaggrin and involucrin) in HaCaT cells. Furthermore, LMFAb increased hyaluronan (HA) production and expression of HA synthases (HAS-1, HAS-2, and HAS-3) but decreased HYBID (HA binding protein involved in HA depolymerization) level in HaCaT cells. These findings demonstrate that LMFAb might promote skin re-epithelization, barrier and moisturizing-related beneficial responses in keratinocytes. This study suggests that LMFAb should be considered a potential starting material for the development of cosmetic or pharmaceutical agents that restore the functions of damaged skin.
RESUMO
In situ CO2 mixing technology is a potential technology for permanently sequestering CO2 during concrete manufacturing processes. Although it has been approved as a promising carbon capture and utilisation (CCU) method, its effect on the leachability of heavy metals from cementitious compounds has not yet been studied. This study focuses on the effect of in situ CO2 mixing of cement paste on the leaching of hexavalent chromium (Cr(VI)). The tank leaching test of the CO2 mixing cement specimen resulted in a Cr(VI) cumulative leaching of 0.614 mg/m2 in 28 d, which is ten times lower than that of the control mixing specimens. The results in thermogravimetric analysis indicated that a relatively significant amount of CrO42- is immobilised as CaCrO4 during the CO2-mixing, and a higher Cr-O extension is observed in the Fourier transform infrared spectra. Furthermore, a portion of the monocarboaluminate is inferred from microstructural analyses to incorporate CrO42- ions. These results demonstrate that in situ CO2 mixing is beneficial not only in reducing CO2 emissions, but also in controlling the leaching of toxic substances.
RESUMO
Since the introduction of transcatheter aortic valve (AV) implantation as a viable option, surgical bioprosthetic AVs have recently started incorporating shorter struts considering future valve-in-valve procedures. However, the effect of leaflet coaptation geometry on the longevity of these valves remains unexplored. To address this gap, we performed a finite element analysis on bioprosthetic AVs with varying strut heights using a two-way fluid-structure interaction method. To establish a baseline, we used a standard height based on a rendered platform image of the CE PERIMOUNT Magna Ease valve from Edward Lifesciences in Irvine, CA. Bovine pericardium properties were assigned to the leaflets, while normal saline properties were used as the recirculating fluid in hemodynamic simulations. The physiological pressure profile of the cardiac cycle was applied between the aorta and left ventricle. We calculated blood flow velocity, effective orifice area (EOA), and mechanical stress on the leaflets. The results reveal that as the strut height increases, the stroke volume increases, leakage volume decreases, and EOA improves. Additionally, the maximum mechanical stress experienced by the leaflet decreases by 62% as the strut height increases to 1.2 times the standard height. This research highlights that a low-strut design in bioprosthetic AVs may negatively affect their durability, which can be useful in design of next-generation bioprosthetic AVs.
RESUMO
Importance: Prospective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking. Objective: To evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy. Design, Setting, and Participants: The POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer. Intervention: Postoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy. Main Outcomes and Measures: The primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion. Results: Of 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients' median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%. Conclusions: Findings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03239613.
Assuntos
Quimiorradioterapia , Hipofracionamento da Dose de Radiação , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Pessoa de Meia-Idade , Adulto , Quimiorradioterapia/efeitos adversos , Histerectomia , Estudos Prospectivos , IdosoRESUMO
Chronic sleep disturbance affects daily functioning, leading to decreased concentration, fatigue, and higher healthcare costs. Traditional insomnia medications are often associated with adverse side effects. This study investigated the efficacy of a novel compound derived from Rhodiola rosea and Nelumbo nucifera extracts (named RNE) in improving sleep quality with fewer side effects. The study included individuals between the ages of 20 and 65 with subthreshold insomnia and evaluated the effects of RNE on sleep, fatigue, and quality of life. Participants took 750 mg of RNE daily at bed-time for two weeks. The study used the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), a sleep diary, the Fatigue Severity Scale (FSS), and the Short Form 36 Health Survey (SF-36) for assessments. Of the 20 participants, 13 completed the study and showed significant improvements in sleep quality. The results showed improvements in ISI and PSQI scores, a 57% reduction in wake-time after sleep onset, and improved sleep efficiency. Although FSS scores remained unchanged, significant improvements were seen in SF-36 physical and mental health scores. The results suggest that RNE is an effective, low-risk option for sleep disturbance, significantly improving sleep quality and overall wellbeing without significant side effects.
Assuntos
Nelumbo , Extratos Vegetais , Qualidade de Vida , Rhodiola , Distúrbios do Início e da Manutenção do Sono , Qualidade do Sono , Humanos , Rhodiola/química , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Nelumbo/química , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Adulto Jovem , Fadiga/tratamento farmacológico , Idoso , Transtornos do Sono-Vigília/tratamento farmacológico , Sono/efeitos dos fármacosRESUMO
Panax ginseng Meyer and Inula japonica Thunb. are well established in traditional medicine and are known for their therapeutic properties in managing a range of ailments such as diabetes, asthma, and cancer. Although P. ginseng and I. japonica can alleviate pulmonary fibrosis (PF), the anti-fibrosis effect on PF by the combination of two herbal medicines remains unexplored. Therefore, this study explores this combined effect. In conditions that were not cytotoxic, MRC-5 cells underwent treatment using the formula combining P. ginseng and I. japonica (ISE081), followed by stimulation with transforming growth factor (TGF)-ß1, to explore the fibroblast-to-myofibroblast transition (FMT). After harvesting the cells, mRNA levels and protein expressions associated with inflammation and FMT-related markers were determined to evaluate the antiinflammation activities and antifibrosis effect of ISE081. Additionally, the anti-migratory effects of ISE081 were validated through a wound-healing assay. ISE081 remarkably reduced the mRNA levels of interleukin (IL)-6, IL-8, α-smooth muscle actin (SMA), and TGF-ß1 in MRC-5 cells and suppressed the α-SMA and fibronectin expressions, respectively. Furthermore, ISE081 inhibited Smad2/3 phosphorylation and wound migration of MRC-5 cells. Under the same conditions, comparing those of ISE081, P. ginseng did not affect the expression of α-SMA, fibronectin, and Smad2/3 phosphorylation, whereas I. japonica significantly inhibited them but with cytotoxicity. The results indicate that the synergistic application of P. ginseng and I. japonica enhances the anti-fibrotic properties in pulmonary fibroblasts and concurrently diminishes toxicity. Therefore, ISE081 has the potential as a prevention and treatment herbal medicine for PF.
Assuntos
Inula , Panax , Fibrose Pulmonar , Humanos , Inula/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Panax/metabolismo , Fibrose , Fibrose Pulmonar/metabolismo , Fibroblastos , Fator de Crescimento Transformador beta1/metabolismo , RNA Mensageiro/metabolismoRESUMO
Skeletal muscle aging results in the gradual suppression of myogenesis, leading to muscle mass loss. However, the specific role of cardiolipin in myogenesis has not been determined. This study investigated the crucial role of mitochondrial cardiolipin and cardiolipin synthase 1 (Crls1) in age-related muscle deterioration and myogenesis. Our findings demonstrated that cardiolipin and Crls1 are downregulated in aged skeletal muscle. Moreover, the knockdown of Crls1 in myoblasts reduced mitochondrial mass, activity, and OXPHOS complex IV expression and disrupted the structure of the mitochondrial cristae. AAV9-shCrls1-mediated downregulation of Crls1 impaired muscle regeneration in a mouse model of cardiotoxin (CTX)-induced muscle damage, whereas AAV9-mCrls1-mediated Crls1 overexpression improved regeneration. Overall, our results highlight that the age-dependent decrease in CRLS1 expression contributes to muscle loss by diminishing mitochondrial quality in skeletal muscle myoblasts. Hence, modulating CRLS1 expression is a promising therapeutic strategy for mitigating muscle deterioration associated with aging, suggesting potential avenues for developing interventions to improve overall muscle health and quality of life in elderly individuals.
Assuntos
Músculo Esquelético , Doenças Musculares , Regeneração , Animais , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Camundongos , Doenças Musculares/metabolismo , Doenças Musculares/etiologia , Doenças Musculares/patologia , Doenças Musculares/genética , Envelhecimento/metabolismo , Desenvolvimento Muscular , Mitocôndrias/metabolismo , Modelos Animais de Doenças , Humanos , Cardiolipinas/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Masculino , Mioblastos/metabolismoRESUMO
BACKGROUND: Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. METHODS: We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6-9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0-29.9%, 30-49.9%, 50-69.9%, 70-79.9%, 80-89.9%, and 90-100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. RESULTS: Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. CONCLUSION: For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.
Assuntos
Metástase Neoplásica , Neoplasias da Próstata , Radio-Oncologistas , Masculino , Humanos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , República da Coreia , Inquéritos e Questionários , Pessoa de Meia-IdadeRESUMO
PURPOSE: There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities. MATERIALS AND METHODS: Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and Embase. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed. RESULTS: A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies. CONCLUSION: Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed.
Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Radiocirurgia , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/mortalidade , Radiocirurgia/métodos , Radiocirurgia/efeitos adversos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Resultado do TratamentoRESUMO
Fine dust concentrations come in direct contact with the human respiratory system, thereby reducing lung function and causing respiratory diseases such as asthma and rhinitis. The aim of this study was to evaluate the efficacy of GHX02 (combination of four herbs [Trichosanthes kirilowii, Prunus armeniaca, Coptis japonica, and Scutellaria baicalensis]), a herbal extract with established efficacy against bronchitis and pulmonary disease, in the treatment of asthma accompanied by rhinitis aggravated by fine dust. Therefore, we constructed an asthma-rhinitis mouse model of Balb/c mice challenged with ovalbumin (OVA) and fine diesel particulate matter, which were administered with three concentrations of GHX02. GHX02 significantly inhibited the increase of total cells and immune cells in bronchoalveolar lavage fluid, lung tissue, and nasal ductal lymphoid tissue (NALT). GHX02 also reduced the severity of histological lung injury and the expression of interleukin (IL)-1α and nuclear factor kappa B (NF-κB), which regulate inflammatory responses. The results indicate that GHX02 inhibited the inflammatory immune response in mice. Therefore, this study highlights the potential of GHX02 as a treatment for patients with asthma accompanied by rhinitis. Balb/c mice were challenged with OVA and PM10D, and then treated with three concentration of GHX02. GHX02 significantly inhibited the increase of total cells, immune cells lymphocytes, neutrophils, and macrophages, as well as their expression in lung tissue. GHX02 significantly inhibited the increase of total cells and immune cells in NALT. GHX02 decreased the severity of histological lung injury, expression of IL-1α and NF-κB. This study suggests the probability that GHX02 is effective for asthma patients with rhinitis by inhibiting inflammatory immune response.
Assuntos
Asma , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Ovalbumina , Material Particulado , Extratos Vegetais , Animais , Asma/tratamento farmacológico , Asma/imunologia , Asma/induzido quimicamente , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Rinite/tratamento farmacológico , Rinite/imunologia , NF-kappa B/metabolismoRESUMO
Focal cortical dysplasia type I (FCD I) is the most common cause of pharmaco-resistant epilepsy with the poorest prognosis. To understand the epileptogenic mechanisms of FCD I, we obtained tissue resected from patients with FCD I epilepsy, and from tumor patients as control. Using whole-cell patch clamp in acute human brain slices, we investigated the cellular properties of fast-spiking interneurons (FSINs) and pyramidal neurons (PNs) within the ictal onset zone. In FCD I epilepsy, FSINs exhibited lower firing rates from slower repolarization and action potential broadening, while PNs had increased firing. Importantly, excitatory synaptic drive of FSINs increased progressively with the scale of cortical activation as a general property across species, but this relationship was inverted towards net inhibition in FCD I epilepsy. Further comparison with intracranial electroencephalography (iEEG) from the same patients revealed that the spatial extent of pathological high-frequency oscillations (pHFO) was associated with synaptic events at FSINs.