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BACKGROUND: Volatile organic compounds (VOC) are major indoor air pollutants. Previous studies reported an association between VOC exposure and allergic diseases. Here, we aimed to explore the relationship between VOC exposure and atopic dermatitis (AD) in adults. METHODS: We prospectively enrolled 31 adult AD patients and 11 healthy subjects as controls. Urine metabolite levels of VOCs, including 1.3-butadiene, acrylamide, benzene, toluene, and xylene, were all determined with liquid chromatography-mass spectrometry. The relationship between AD and log-transformed urine levels of VOC metabolites were examined using a multivariate linear regression model adjusted for age and sex. We also treated mouse bone marrow-derived cells (BMMCs) with 1,3-butadiene and toluene and measured the release of ß-hexosaminidase. RESULTS: Our results demonstrated that creatinine-corrected urine levels of N-Acetyl-S- (3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA), and N-Acetyl-S-(benzyl)-L-cysteine (BMA) were all elevated in AD patients compared with controls. In a multivariate linear regression model, creatinine-corrected urine levels of BMA (a toluene metabolite) and DHBMA (a 1,3-butadiene metabolite) appeared elevated in AD patients, although statistical significance was not reached after correction for multiple comparisons. In addition, 1,3-butadiene and toluene could stimulate BMMCs to degranulate as much as compound 48/80. CONCLUSIONS: Some VOCs, such as 1,3-butadiene and toluene, might be associated with AD pathogenesis in adults.
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OBJECTIVES: The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and dacomitinib in this setting. MATERIALS AND METHODS: Between September 2020 and March 2023, we retrospectively recruited patients diagnosed with advanced-stage EGFR-mutant NSCLC who were treated with first-line irreversible EGFR-TKIs. The enrolled patients were assigned to two groups based on whether they received afatinib or dacomitinib. RESULTS: A total of 101 patients were enrolled in the study (70 to afatinib and 31 to dacomitinib). The partial response rates (PR) for first-line treatment with afatinib and dacomitinib were 85.7 and 80.6% (p = 0.522). The median progression-free survival (PFS) (18.9 vs. 16.3 months, p = 0.975) and time to treatment failure (TTF) (22.7 vs. 15.9 months, p = 0.324) in patients with afatinib and dacomitinib treatment were similar. There was no significant difference observed in the median PFS (16.1 vs. 18.9 months, p = 0.361) and TTF (32.5 vs. 19.6 months, p = 0.182) between patients receiving the standard dose and those receiving the reduced dose. In terms of side effects, the incidence of diarrhea was higher in the afatinib group (75.8% vs. 35.5%, p < 0.001), while the incidence of paronychia was higher in the dacomitinib group (58.1% vs. 31.4%, p = 0.004). The PFS (17.6 vs. 24.9 months, p = 0.663) and TTF (21.3 vs. 25.1 months, p = 0.152) were similar between patients younger than 75 years and those older than 75 years. CONCLUSION: This study showed that afatinib and dacomitinib had similar effectiveness and safety profiles. However, they have slightly different side effects. Afatinib and dacomitinib can be safely administered to patients across different age groups with appropriate dose reductions.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Quinazolinonas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Afatinib/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/efectos adversos , Resultado del Tratamiento , Receptores ErbB , MutaciónRESUMEN
BACKGROUND: Limited information is available for guiding the management of upper urinary tract (UUT) urothelial carcinoma with squamous differentiation (UC-SqD). We did not even know about the difference between pure urothelial carcinoma (UC) and UC-SqD in the UUT regardless of treatment policy and prognosis. Instead of direct comparisons against each other, we included the third UUT malignancy, squamous cell carcinoma (SCC). This three-way-race model allows us to more clearly demonstrate the impact of squamous cell transformation on patient outcomes in UUT malignancy. METHODS: We retrospectively analysed 327 patients with UC, UC-SqD, or SCC who underwent radical nephroureterectomy with bladder cuff excision (RNU) at Taichung Veterans General Hospital, Taichung, Taiwan, between January 2006 and December 2013. A Kaplan-Meier survival analysis was used to evaluate the relationship between patient outcomes and histology. Multivariate Cox proportional hazards modelling was also used to predict patient prognoses. RESULTS: The five-year postoperative cancer-specific survival (CSS) rates were 83.6% (UC), 74.4% (UC-SqD), and 55.6% (SCC), and the 5-year recurrence-free survival (RFS) rates were 87.7% (UC), 61.5% (UC-SqD), and 51.9% (SCC). UC patients had significantly better 5-year RFS than UC-SqD and SCC patients (P = 0.001 and P < 0.0001, respectively). Patients with pure UC had significantly better 5-year CSS than SCC patients (P = 0.0045). SCC or UC-SqD did not independently predict disease-specific mortality (HR 0.999, p = 0.999; HR 0.775, p = 0.632, respectively) or disease recurrence compared to pure UC (HR 2.934, p = 0.239; HR 1.422, p = 0.525, respectively). Age, lymphovascular invasion (LVI), and lymph node (LN) status independently predicted CSS, while pathological tumour stage, LN status, and LVI predicted RFS. CONCLUSIONS: SCC and UC-SqD are not independent predictors of survival outcomes in patients with UUT tumours. However, they are associated with other worse prognostic factors. Hence, different treatments are needed for these two conditions, especially for SCC.
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Carcinoma de Células Escamosas , Carcinoma de Células Transicionales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Humanos , Nefroureterectomía , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/cirugía , Estudios Retrospectivos , Neoplasias Ureterales/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Neoplasias Urológicas/cirugía , Neoplasias Urológicas/patología , Células Epiteliales/patología , Carcinoma de Células Escamosas/cirugíaRESUMEN
BACKGROUND: We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population. METHODS: We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. RESULTS: In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. CONCLUSION: Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.
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Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Trastornos Respiratorios , Humanos , Adulto , Oscilometría , Enfermedades Pulmonares Intersticiales/diagnóstico , Pruebas de Función Respiratoria , Artritis Reumatoide/complicacionesAsunto(s)
Dermatitis Atópica , Trampas Extracelulares , MicroARNs , Humanos , Piel , Inflamación , MicroARNs/genéticaRESUMEN
An investigation of the chemical composition of a Formosan soft coral Cespitularia sp. led to the discovery of one new verticillene-type diterpenoid, cespitulactam M (1); one new eudesmane sesquiterpenoid, cespilamide F (2); and three new hydroperoxysteroids (3-5) along with twelve known analogous metabolites (6-17). In addition, one new derivative, cespitulactam M-6,2'-diacetate (1a), was prepared from compound 1. The structures were determined by detailed spectroscopic analyses, particularly HRESIMS and NMR techniques. Moreover, the in vitro cytotoxicity, anti-inflammatory, and antibacterial activity of 1-17 and 1a were evaluated.
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Antozoos , Diterpenos , Sesquiterpenos de Eudesmano , Sesquiterpenos , Animales , Antozoos/química , Sesquiterpenos de Eudesmano/química , Espectroscopía de Resonancia Magnética , Diterpenos/química , Sesquiterpenos/química , Estructura MolecularRESUMEN
The aim of current single-center study was to compare the short-term outcome of suction and gauze wiping alone versus the irrigation and suction technique for peritoneal decontamination among patients who underwent laparoscopic repair of PPU. Using data from our institution's prospectively maintained database, 105 patients who underwent laparoscopic repair were enrolled in this study. The participants were further divided into the group who received peritoneal irrigation (irrigation group, n = 67) and group who received gauze wiping and suction only (suction only group, n = 38). The irrigation group had a longer operative time (140 vs. 113 min, p = 0.0001), higher number of drainage tubes (38.8% vs. 0%, p < 0.0001) and a higher incidence of intra-abdominal abscess (10.4% vs. 0%, p = 0.0469) than the suction only group. Peritoneal irrigation may be associated with a prolonged operative time and a higher number of abdominal drains. Meanwhile, gauze wiping and suction may be sufficient for peritoneal decontamination during the laparoscopic repair of PPU as further infectious complications are not observed.
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Laparoscopía , Úlcera Péptica Perforada , Humanos , Succión/métodos , Descontaminación , Resultado del Tratamiento , Laparoscopía/métodos , Úlcera Péptica Perforada/complicaciones , Complicaciones Posoperatorias/etiologíaRESUMEN
The present chemical investigation on the organic extract of the soft coral Sarcophyton cinereum has contributed to the isolation of four new cembranoids: 16ß- and 16α-hydroperoxyisosarcophytoxides (1 and 2), 16ß- and 16α-methoxyisosarcophytoxides (3 and 4), and a known cembranoid, lobocrasol (5). The structures of all isolates were elucidated by detailed spectroscopic analysis. Their structures were characterized by a 2,5-dihydrofuran moiety, of which the relative configuration was determined by DU8-based calculation for long-range coupling constants (4JH,H). The cytotoxicity and immunosuppressive activities of all isolates were evaluated in this study.
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Antozoos , Diterpenos , Animales , Antozoos/química , Diterpenos/química , Estructura MolecularRESUMEN
Echinocystic acid (EA), a pentacyclic triterpene, exhibits anti-inflammatory, antioxidant, and analgesic activities to counteract pathological effects in various diseases. Here, we aimed to determine the immunomodulatory effect of EA on zymosan-induced arthritis in SKG mice and how it would influence Th17 differentiation and human rheumatoid arthritis fibroblast-like synoviocytes inflammation. Our results showed that EA (10 and 25 mg/kg) attenuated arthritis symptoms, including high arthritis scores, infiltrating inflammatory cells, synovial hyperplasia, bone erosion, and the high levels of proinflammatory cytokines, such as TNF-α, interleukin (IL)-6, and IL-1ß in paw tissues, and reduced the number of splenic Th17 cells. Mechanistically, we found that in vitro treatment of EA inhibited both IL-6- and transforming growth factor-ß (TGF-ß)-induced Th17 cell differentiation by suppressing the phosphorylation of signal transducers and transcriptional activators, especially STAT3. In line with the in vivo result, EA significantly reduced the protein and mRNA expression of IL-6 and IL-1ß in human RA-FLA cells, MH7A cells. Furthermore, the production of both cytokines was confirmed with the downregulation of mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathways under the stimulation of TNF-α. In conclusion, these findings revealed that EA was capable of amelioration of arthritic disorders in SKG mice through inhibiting Th17 cell differentiation and synovial fibroblast inflammation, supporting that EA is a promising therapeutic candidate for treating RA patients.
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Artritis Experimental , Artritis Reumatoide , Sinoviocitos , Humanos , Animales , Ratones , Sinoviocitos/metabolismo , Sinoviocitos/patología , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Células Th17 , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/genética , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Citocinas/genética , Citocinas/metabolismo , Fibroblastos , Diferenciación CelularRESUMEN
Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, and antitumoral activities. LF has been shown to function in immunoregulatory activities in ovalbumin (OVA)-induced delayed type hypersensitivity (DTH) in mice. Hence, the purpose of this study was to investigate the roles of LF in AHR and the functions of dendritic cells (DCs) and Th2-related responses in asthma. Twenty 8-week-old male BALB/c mice were divided into normal control (NC), ovalbumin (OVA)-sensitized, and OVA-sensitized with low dose of LF (100 mg/kg) or high dose of LF (300 mg/kg) treatment groups. The mice were challenged by intranasal instillation with 5% OVA on the 21st to 27th day after the start of the sensitization period. The AHR, cytokines in bronchoalveolar lavage fluid, and pulmonary histology of each mouse were measured. Serum OVA-specific IgE and IgG1 and OVA-specific splenocyte responses were further detected. The results showed that LF exhibited protective effects in ameliorating AHR, as well as lung inflammation and damage, in reducing the expression of Th2 cytokines and the secretion of allergen-specific antibodies, in influencing the functions of DCs, and in decreasing the level of Th2 immune responses in a BALB/c mouse model of OVA-induced allergic asthma. Importantly, we demonstrated that LF has practical application in reducing DC-induced Th2 cell responses in asthma. In conclusion, LF exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma. These results suggest that LF may act as a supplement to prevent asthma-induced lung injury and provide an additional agent for reducing asthma severity.
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Asma , Lactoferrina , Células Th2 , Animales , Masculino , Ratones , Asma/inducido químicamente , Asma/tratamiento farmacológico , Citocinas/metabolismo , Lactoferrina/farmacología , Lactoferrina/uso terapéutico , Lactoferrina/metabolismo , Ratones Endogámicos BALB C , Ovalbúmina , Células Th2/efectos de los fármacos , Células Th2/metabolismo , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismoRESUMEN
The study aimed to investigate the therapeutic impact of intravesical instillation of dehydrated human amnion-chorion membrane (HACM) extracts based on the primary pathological feature of interstitial cystitis (IC). We divided 15 female Sprague-Dawley rats into three groups: sham control, IC, and treatment group. IC was induced by 400-µL lipopolysaccharide (1 µg/µL), and it was replaced with normal saline in the sham control group. After IC induction, 300 µL dehydrated HACM extracts (3 mg/kg) were instilled into rats' urinary bladder weekly for 3 weeks. General histology, inflammatory cytokines, NF-κB, oxidative markers, and western blots results were examined. The urothelial denudation, mast-cell infiltration, and tissues fibrosis were all ameliorated. The elevated TNF-α, IL-1ß, IL-6, IL-8, and NF-κB were all down-regulated by dehydrated HACM extracts (p < 0.05). For reactive oxygen species, increased malondialdehyde, decreased superoxide dismutase, and decreased glutathione peroxidase were all reversed (p < 0.05). In apoptosis of IC, elevated Bax and suppressed Bcl-2 were improved (p < 0.05) after instillation. In fibrosis, dysregulated TGFß/R-Smads/Snail was corrected by the instillation of dehydrated HACM (p < 0.05). In conclusion, dehydrated HACM extracts could be a powerful remedy in treating IC by reconstructing the damaged urothelium, reducing mast-cell infiltration and inflammatory reactions, and ameliorating fibrotic changes.
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Background and Objectives: This single-center study aimed to assess the role of laparoscopic greater curvature plication (LGCP) in bariatric surgery. Materials and Methods: Using data from our institution's prospectively maintained database, we identified adult patients with obesity who underwent either laparoscopic sleeve gastrectomy (LSG) or LGCP between January 2012 and July 2017. In total, 280 patients were enrolled in this study. Results: The body mass index was higher in the LSG group than in the LGCP group (39.3 vs. 33.3, p < 0.001). Both groups achieved significant weight loss during the 3-year follow-up (p < 0.001). The weight-reduction rate was higher in the LSG group than in the LGCP group 6, 12, and 24 months postoperatively (p = 0.001, 0.001, and 0.012, respectively). The reoperation rate of the LGCP group was higher than that of the LSG group (p = 0.001). No deaths were recorded in either group. Conclusions: Although both the LGCP and LSG groups achieved significant weight loss over three years, the LGCP group demonstrated a lower weight-reduction rate and a higher reoperation rate than the LSG group. Thus, it is necessary to reassess the role of LGCP in bariatric surgery, particularly when LSG is a feasible alternative.
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Cirugía Bariátrica , Gastroplastia , Laparoscopía , Obesidad Mórbida , Adulto , Índice de Masa Corporal , Gastrectomía , Humanos , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Diabetes mellitus (DM) is an important risk factor in patients with end-stage renal disease (ESRD). DM is associated with the development of cardiovascular diseases, such as atrial fibrillation (AF), due to poor glycemic control. However, few studies have focused on the risk of developing ESRD among DM patients with and without AF. This study evaluated ESRD risk among DM patients with and without AF in Taiwan. Data were retrieved from one million patients randomly sampled from Taiwan's National Health Insurance Research Database, including 6,105 DM patients with AF propensity score-matched with 6,105 DM patients without AF. Both groups were followed until death, any dialysis treatment, or December 31, 2013, whichever occurred first. AF was diagnosed by a qualified physician according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), using the diagnostic code 427.31. Patients aged <20 years or diagnosed with ESRD before the index date were excluded. A Cox proportional hazard regression model was used to calculate the relative ESRD risk. Among DM patients, those with AF have more comorbidities than those without AF. We also found a 1.18-fold (95% confidence interval [CI]: 1.01-1.46) increase in ESRD risk among patients with AF compared with those without AF. In addition, DM patients with hypertension, chronic kidney disease (CKD), or higher Charlson Comorbidity Index scores also have significantly increased ESRD risks than those without these complications. A 1.39-fold (95% CI: 1.04-1.86) increase in risk was observed for patients with AF among the non-CKD group. Our findings suggest that patients with DM should be closely monitored for irregular or rapid heart rates.
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Fibrilación Atrial , Diabetes Mellitus , Fallo Renal Crónico , Insuficiencia Renal Crónica , Adulto , Humanos , Incidencia , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , TaiwánRESUMEN
Currently, medication for benign prostate hyperplasia (BPH) and prostate cancer (PCa) are mainly based on modulating the hormone and nervous systems. However, side effects often affect patients, and might decrease their commitment to continuing the medication and lower their quality of life. Some studies have indicated that chronic inflammation might be the cause of BPH and PCa. Based on this hypothesis, the effect of phloretin, a potent anti-inflammatory and anti-oxidative flavonoid, has been researched since 2010. Results from animal and in-vitro studies, obtained from databases, also indicate that the use of phloretin in treating BPH and PCa is promising. Due to its effect on inflammatory cytokines, apoptosis or anti-apoptosis, reactive oxygen species, anti-oxidant enzymes and oxidative stress, phloretin is worthy of further study in human clinical trials regarding safety and effective dosages.
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BACKGROUND/AIM: Prostate cancer (PC) is one of the major diseases that affects male health and ranks as the second most frequent cancer in men worldwide. Although most newly-diagnosed PCs are well-differentiated tumors with a high cure probability, there are some patients with aggressive malignancies that show potential for recurrence and metastasis. Cytotoxic T lymphocytes are a specific immune effector cell population that mediates immune responses against cancer. MATERIALS AND METHODS: In the present study, the cytotoxicity of peripheral blood mononuclear cells (PBMCs)-derived γδ T cells and cytokine-induced killer (CIK) cells in combination with chemoradiotherapy against PC cells was evaluated using Alamar blue cell viability and cell membrane permeability assays. RESULTS: Advanced PC-3 cells, which were more resistant to docetaxel (Doc), also showed higher viability following pretreatment with radiation. The cell proliferation inhibition was significantly increased upon additional γδ T or CIK treatment. Furthermore, the proportion of apoptotic cells was significantly (p<0.05) increased in the Doc-γδ T cell co-treatment group as compared with the Doc or γδ T cell treated alone group. CONCLUSION: γδ T cell therapy may provide additional benefit compared to traditional chemoradiotherapy for PC treatment.
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Células Asesinas Inducidas por Citocinas , Neoplasias Primarias Secundarias , Neoplasias de la Próstata , Quimioradioterapia , Docetaxel/farmacología , Humanos , Recuento de Linfocitos , Masculino , Neoplasias de la Próstata/terapiaRESUMEN
The use of multiple drugs simultaneously targeting DNA is a promising strategy in cancer therapy for potentially overcoming single drug resistance. In support of this concept, we report that a combination of actinomycin D (ActD) and echinomycin (Echi), can interact in novel ways with native and mismatched DNA sequences, distinct from the structural effects produced by either drug alone. Changes in the former with GpC and CpG steps separated by a A:G or G:A mismatch or in a native DNA with canonical G:C and C:G base pairs, result in significant asymmetric backbone twists through staggered intercalation and base pair modulations. A wobble or Watson-Crick base pair at the two drug-binding interfaces can result in a single-stranded 'chair-shaped' DNA duplex with a straight helical axis. However, a novel sugar-edged hydrogen bonding geometry in the G:A mismatch leads to a 'curved-shaped' duplex. Two non-canonical G:C Hoogsteen base pairings produce a sharply kinked duplex in different forms and a four-way junction-like superstructure, respectively. Therefore, single base pair modulations on the two drug-binding interfaces could significantly affect global DNA structure. These structures thus provide a rationale for atypical DNA recognition via multiple DNA intercalators and a structural basis for the drugs' potential synergetic use.
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ADN , Emparejamiento Base , ADN/química , ADN/genética , Enlace de Hidrógeno , Estructura Molecular , Conformación de Ácido NucleicoRESUMEN
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint deformity and disability. Deer velvet antler (DA), a traditional Chinese medicine, has been used to treat various types of arthritis for several thousands of years, but the underlying mechanisms are unknown. Herein, we investigated the anti-arthritic and anti-inflammatory effects of DA in vitro and in vivo. The ethyl acetate layer of DA ethanol extract (DA-EE-EA) was used to treat tumor necrosis factor (TNF)-[Formula: see text]-stimulated fibroblast-like synoviocyte MH7A cells, collagen-induced arthritis DBA/1 mice, and SKG mice with zymosan-induced arthritis. DA-EE-EA reduced nitric oxide production, prostaglandin E2 levels, and levels of pro-inflammatory cytokines including interleukin (IL)-1[Formula: see text], IL-6, and IL-8 in MH7A cells. DA-EE-EA also downregulated the phosphorylation of mitogen-activated protein kinase p38 and c-Jun N-terminal kinase and the translocation of nuclear factor kappa B p65. Intraperitoneal injection of DA-EE-EA for 3 weeks substantially reduced clinical arthritis scores in vivo models. Pathohistological images of the hind paws showed that DA-EE-EA reduced immune cell infiltration, synovial hyperplasia, and cartilage damage. The levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, IL-1[Formula: see text], IL-6, IL-8, IL-17A, and interferon-gamma, decreased in the hind paw homogenates of DA-EE-EA-treated mice. We also identified several potential components, such as hexadecanamide, oleamide, erucamide, and lysophosphatidylcholines, that might contribute to the anti-inflammatory effects of DA-EE-EA. In conclusion, DA-EE-EA has the potential to treat RA by regulating inflammatory responses. However, the individual components of DA-EE-EA and the underlying anti-inflammatory mechanisms need further investigation in future studies.
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Cuernos de Venado , Artritis Experimental , Artritis Reumatoide , Ciervos , Sinoviocitos , Animales , Antiinflamatorios/farmacología , Cuernos de Venado/metabolismo , Cuernos de Venado/patología , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Citocinas/metabolismo , Ciervos/metabolismo , Fibroblastos/metabolismo , Humanos , Interleucina-6 , Interleucina-8 , Ratones , Ratones Endogámicos DBA , Sinoviocitos/metabolismo , Sinoviocitos/patología , Factor de Necrosis Tumoral alfaRESUMEN
Crassolide, a cembranoid diterpene extracted from the soft coral Lobophytum crissum, has been proven to possess antioxidant and immunomodulatory properties. In the present study, we assessed the anticancer effects of crassolide on human H460 non-small-cell lung cancer (NSCLC) cells. We found that crassolide exerted cytotoxic effects on H460 cancer cells in vitro, inducing G2/M phase arrest and apoptosis. In addition, in H460 cells exposed to crassolide, the expression of the autophagy-related proteins LC3-II and beclin was increased, while the expression of p62 was decreased. Moreover, inhibiting autophagy with chloroquine (CQ) suppressed the crassolide-induced G2/M arrest and apoptosis of H460 cells. Moreover, we also found that crassolide induced endoplasmic reticulum (ER) stress in lung cancer cells by increasing the expression of ER stress marker proteins and that the crassolide-induced G2/M arrest, apoptosis, and autophagy were markedly attenuated by the ER stress inhibitor 4-phenylbutyric acid (4-PBA). Furthermore, we found that crassolide promoted reactive oxygen species (ROS) production by H460 cells and that the ROS inhibitor N-acetylcysteine (NAC) decreased the crassolide-induced ER stress, G2/M arrest, apoptosis, and autophagy. In conclusion, our findings show that crassolide inhibits NSCLC cell malignant biological behaviors for the first time, suggesting that this effect may be mechanistically achieved by inducing G2/M arrest, apoptosis, and autophagy through ROS accumulation, which activates the ER stress pathway. As a result of our findings, we now have a better understanding of the molecular mechanism underlying the anticancer effect of crassolide, and we believe crassolide might be a candidate for targeted cancer therapy.
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Carcinoma de Pulmón de Células no Pequeñas , Diterpenos , Neoplasias Pulmonares , Apoptosis , Autofagia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Diterpenos/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Psoriasis is an immune-mediated skin disease with a worldwide prevalence of 2-4% that causes scaling erythematous skin lesions. It is a chronic relapsing and complex multifactorial disease that often necessitates long-term therapy. Despite various novel therapies, psoriasis remains a treatable but non-curable disease. Because the antitussive medication dextromethorphan (DXM) can inhibit murine bone marrow and human monocytes and slow the progression of arthritis in mice with type II collagen-induced arthritis, we explored whether the oral administration of DXM to mice with imiquimod (IMQ)-induced psoriasis can effectively alleviate psoriasis symptoms and improve immune regulation. Herein, we examined the therapeutic effects of DXM on psoriasis and its potential mechanisms of action in an IMQ-induced psoriasis mice model. We found that an oral dose of DXM (10 mg/kg) could more significantly reduce psoriasis symptoms compared with intraperitoneal injection. Seven days after the oral administration of DXM, the Psoriasis Area and Severity Index (PASI) score was significantly decreased compared with that in the vehicle group. Furthermore, DXM treatment also significantly ameliorated the psoriasis symptoms and the histopathological features of psoriasis, including stratum corneum thickening, desquamation, and immune cell infiltration. Additionally, DXM reduced the mRNA levels of the cytokines TNF-α, IL-6, IL-17A, and IL-22 in skin and the percentage of IL-17A and IL-22 producing T cell receptor γδ T cells (TCRγδT). Taken together, our research demonstrated that DXM could inhibit keratinocyte proliferation and alleviate psoriasis symptoms, which suggests the potential application of DXM in the treatment of chronic inflammation and autoimmune diseases.
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PURPOSE: Pendulone, an isoflavone compound, is known to act against human cancer cells. However, its role in human non-small cell lung cancer (NSCLC) and the exact molecular mechanisms of action have never been reported. METHODS: We investigated the effects of pendulone on cell proliferation and apoptosis in human NSCLC H1299 cells. Cell viability was examined using the methyl-thiazol-diphenyl-tetrazolium (MTT) assay. Flow cytometry was employed to evaluate apoptotic indices such as the cell cycle, mitochondrial membrane potential, cytochrome c release, caspase activity, and death receptor expression. The expression of proteins related to the cell cycle and apoptosis were analyzed by Western blot analysis. RESULTS: Pendulone significantly decreased H1299 cell viability by inducing endoplasmic reticulum (ER) stress through the accumulation of reactive oxygen species (ROS). Pendulone induced the expression of ER stress-associated proteins, such as ATF4 and CHOP, which promoted the expression of death receptors. Activation of caspase 8 induced extrinsic pathway apoptosis. Pendulone also caused the loss of mitochondrial membrane potential, inhibited the anti-apoptotic proteins BCL-2 and activated the pro-apoptotic protein BAX, which promoted the release of cytochrome c to activate caspase 9. Antioxidant N-acetylcysteine (NAC), with its ROS-suppressive property, reversed pendulone-induced ER stress and cell apoptosis. CONCLUSION: Our findings provide evidence that pendulone induces apoptosis by inducing ER stress through ROS accumulation and mitochondrial dysfunction in NSCLC cell lines.