RESUMEN
Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis-related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti-endoplasmic reticulum (ER) stress, antioxidant and anti-inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium-potassium-chloride co-transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with-no-lysine kinase-4 (WNK4) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)-induced ALI model in A549 cells, considering the regulation of ER stress, WNK4-SPAK-NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK-8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro-inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca2+ in A549 cells was determined using Fluo-4 AM. AEDS attenuates LPS-induced inflammation, which is associated with increased pro-inflammatory cytokine expression and activation of the WNK4-SPAK-NKCC1 pathway. AEDS inhibits the WNK4-SPAK-NKCC1 pathway by regulating of Bcl-2, IP3R and intracellular Ca2+. WNK4 expression levels are significantly higher in the WNK4-overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS-induced inflammation by inhibiting the WNK4-SPAK-NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI.
Asunto(s)
Estrés del Retículo Endoplásmico , Inflamación , Lipopolisacáridos , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Miembro 2 de la Familia de Transportadores de Soluto 12 , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Células A549 , Inflamación/tratamiento farmacológico , Inflamación/patología , Inflamación/metabolismo , Miembro 2 de la Familia de Transportadores de Soluto 12/metabolismo , Miembro 2 de la Familia de Transportadores de Soluto 12/genética , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Extractos Vegetales/farmacología , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Antiinflamatorios/farmacologíaRESUMEN
In recent years, the search for natural compounds with therapeutic properties has gained momentum, with marine organisms emerging as rich sources of bioactive substances [...].
RESUMEN
As a physiological defense mechanism, inflammation is a complex response to harmful stimuli [...].
RESUMEN
BACKGROUND: COVID-19 vaccines have reduced the risk of disease progression to respiratory failure or death. However, in patients with breakthrough infections requiring invasive mechanical ventilation, the effect of prior COVID-19 vaccination on mortality remains inconclusive. METHOD: We retrospectively analyzed data on patients intubated due to COVID-19 pneumonia between May 1, 2022 and October 31, 2022. Receipt of two or more doses of vaccine were considered as fully vaccinated. The primary outcome was the time from intubation to all-cause intensive care unit (ICU) mortality. RESULT: A total of 84 patients were included (40 fully vaccinated versus 44 controls). The baseline characteristics, including age, comorbidities, and Sequential Organ Failure Assessment (SOFA) score on the day of intubation were similar between the two groups. The difference in ICU mortality rate between the fully vaccinated and control groups was not significant (35 % vs. 25 %, P = 0.317; hazard ratio with 95 % confidence interval = 1.246 (0.575-2.666), P = 0.571). The SOFA score (hazard ratio: 1.319, P = 0.001) and body mass index (BMI) (hazard ratio: 0.883, P = 0.022) were significantly associated with ICU mortality. CONCLUSION: Being fully vaccinated was not associated with a mortality benefit in intubated patients with COVID-19. A higher SOFA score on the day of intubation and lower BMI were poor prognostic factors.
Asunto(s)
COVID-19 , Síndrome de Dificultad Respiratoria , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Taiwán/epidemiología , Estudios Retrospectivos , Unidades de Cuidados Intensivos , VacunaciónRESUMEN
Inflammation is one of the body's most complex physiological defense mechanisms against harmful substances [...].
RESUMEN
OBJECTIVE: This study aimed to investigate (1) the temporal pattern of ferroptosis, an iron-dependent cell death, in ligation-induced rat periodontitis and (2) the effect of ferrostatin-1, a ferroptosis inhibitor, on the model. BACKGROUND: Ferroptosis may contribute to various diseases. However, the role of ferroptosis in periodontitis is still fully understood. METHODS: In the first experiment, 25 rats with ligation-induced periodontitis were sacrificed on days 0, 1, 2, 7, and 10. Gingivae were obtained to determine tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and ferroptotic biomarkers, including solute carrier family 3 member 2 (SLC3A2) and solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (Gpx4), via immunoblotting. Using microcomputed tomography (µCT) and histology, the periodontal soft and hard tissue lesions, including dental alveolar bone crest level, bony characteristics of the surrounding alveolus, periodontal tissue inflammation, and periodontal tissue losses, were evaluated. In study two, 16 rats with induced periodontitis were grouped according to ferrostatin-1 treatment. The rats were intraperitoneally injected with solvent or ferrostatin-1 (1.5 mg/kg/day) 1 day before ligation and sacrificed on days 7 and 10. Gingival protein changes and periodontal tissue damage were also examined. RESULTS: In study one, SLC3A2/SLC7A11 and Gpx4 decreased since day 1; however, TNF-α/IL-1ß increased on days 7 and 10. Moreover, the µCT/histology revealed resorptive bony characteristics, inflamed gingival tissue, and periodontal attachment loss. In study two, ferrostatin-1-injected rats exhibited significantly increased SLC3A2/SLC7A11 and Gpx4 but decreased TNF-α/IL-1ß than vehicle rats. They also revealed lessened bone resorption, tissue inflammation, and attachment loss. CONCLUSION: This study highlights the role of ferroptosis, via the system Xc/Gpx4 pathway, in experimental periodontitis and may serve as a regulatory strategy.
Asunto(s)
Ferroptosis , Periodontitis , Ratas , Animales , Factor de Necrosis Tumoral alfa/metabolismo , Microtomografía por Rayos X , Periodontitis/metabolismo , InflamaciónRESUMEN
Oral cancer is a prevalent global issue, with oral squamous cell carcinoma constituting the majority of cases. Standard treatments like surgery, radiotherapy, and chemotherapy are available but may have adverse effects. Molecular gene therapy, focusing on genetic mutations linked to oral cancer, presents a promising alternative.In this study, we evaluated 27 chemotherapeutic drugs and 63 Chinese herbal medicines for their effectiveness, categorized them by their cellular mechanisms, and identified potential adjuvant therapy candidates for oral cancer. Our findings highlight the impact of natural flavonoids on oral cancer cells, inducing apoptosis, and confirming their potential in molecular genetic analysis. In conclusion, the natural compounds present in Chinese herbal medicine, particularly flavonoids, offer a promising avenue to target specific genetic mutations in oral cancer cells. This approach may reduce the risks associated with oral cancer treatment and pave the way for innovative adjuvant therapies.
RESUMEN
BACKGROUND: There is a lack of published research on the impact of the first wave of the COVID-19 pandemic in Taiwan. We investigated the mortality risk factors among critically ill patients with COVID-19 in Taiwan during the initial wave. Furthermore, we aim to develop a novel AI mortality prediction model using chest X-ray (CXR) alone. METHOD: We retrospectively reviewed the medical records of patients with COVID-19 at Taipei Tzu Chi Hospital from May 15 to July 15 2021. We enrolled adult patients who received invasive mechanical ventilation. The CXR images of each enrolled patient were divided into 4 categories (1st, pre-ETT, ETT, and WORST). To establish a prediction model, we used the MobilenetV3-Small model with "Imagenet" pretrained weights, followed by high Dropout regularization layers. We trained the model with these data with Five-Fold Cross-Validation to evaluate model performance. RESULT: A total of 64 patients were enrolled. The overall mortality rate was 45%. The median time from symptom onset to intubation was 8 days. Vasopressor use and a higher BRIXIA score on the WORST CXR were associated with an increased risk of mortality. The areas under the curve of the 1st, pre-ETT, ETT, and WORST CXRs by the AI model were 0.87, 0.92, 0.96, and 0.93 respectively. CONCLUSION: The mortality rate of COVID-19 patients who receive invasive mechanical ventilation was high. Septic shock and high BRIXIA score were clinical predictors of mortality. The novel AI mortality prediction model using CXR alone exhibited a high performance.
Asunto(s)
COVID-19 , Adulto , Humanos , Pandemias , Pronóstico , Estudios Retrospectivos , Rayos X , Inteligencia ArtificialRESUMEN
Oral cancer, a type of head and neck cancer, can pose a significant risk of death unless diagnosed and treated early. Alternative treatments are urgently needed owing to the high mortality rate, limitations of conventional treatments, and many complications. The anthraquinone compound chrysophanol acts as a tumor suppressor on some types of cancer cells. To date, it has not been clarified how chrysophanol affects human tongue squamous carcinoma. This study was aimed to examine the effects of chrysophanol on oral cancer treatment. The results show that chrysophanol caused cell death, reduced the expression of the mammalian target of rapamycin (mTOR)/peroxisome proliferator-activated receptor-alpha (PPAR-α), and increased reactive oxygen species (ROS) production. We also used two ion chelators, deferoxamine (DFO) and liproxstatin-1 (Lipro), to further determine whether chrysophanol inhibits cell growth and regulates mTOR/PPAR-α expression and ROS production, both of which are involved in iron homeostasis. The results show that DFO and Lipro reversed the increase in cell death, downregulation of mTOR/PPAR-α, and decrease in ROS accumulation. In conclusion, chrysophanol inhibits the growth of oral squamous cell carcinoma cells by modulating mTOR/PPAR-α and by causing ROS accumulation.
RESUMEN
Introduction: Asthma is one of the major public health problems that imposes a great burden on societal, financial, and healthcare around the world. Asthma poorly affects the health-related quality of life and daily activities of patients. Treatment of asthma, including inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), mainly aims to improve the lung function and reduce symptoms and exacerbations. Current treatment regimens are symptom-based strategies, and the status of airway inflammation after treatment is yet unknown. We conducted this study to understand the comprehensive inflammation or airway remodeling status of patients after ICS-LABA treatment through RNA transcriptome analysis. Materials and methods: Eight newly diagnosed asthmatic patients and two healthy subjects were recruited in this study. Asthmatic patients underwent blood tests, lung function test, and RNA transcriptome analysis before and after ICS-LABA treatment. Results: In comparison with healthy subjects, pretreatment asthmatic patients had higher expression of protein tyrosine kinase and related signaling pathways. After ICS-LABA treatment, the expression of nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor were downregulated. However, the post-treatment asthmatic patients still had higher expression of cysteine-type endopeptidase, endodeoxyribonuclease, apolipoprotein, and unfolded protein was still upregulated than healthy subjects. Conclusions: The combination of ICS/LABAs decreased airway inflammatory and remodeling pathways. However, allergen stimulation-related pathways were still upregulated in patients after ICS/LABA treatment. The combination of medication and allergen removal is a complete strategy for asthma.
Asunto(s)
Asma , Calidad de Vida , Humanos , Administración por Inhalación , Quimioterapia Combinada , Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Asma/genética , Perfilación de la Expresión Génica , Inflamación/tratamiento farmacológico , Inflamación/genética , Alérgenos/uso terapéutico , Proteínas Tirosina Quinasas , ARNRESUMEN
Coumarin was first discovered in Tonka bean and then widely in other plants. Coumarin has an anticoagulant effect, and its derivative, warfarin, is a vitamin K analogue that inhibits the synthesis of clotting factors and is more widely used in the clinical treatment of endovascular embolism. At present, many artificial chemical synthesis methods can be used to modify the structure of coumarin to develop many effective drugs with low toxicity. In this study, we investigated the effects of six coumarin derivatives on the platelet aggregation induced by adenosine diphosphate (ADP). We found that the six coumarin derivatives inhibited the active form of GPIIb/IIIa on platelets and hence inhibit platelet aggregation. We found that 7-hydroxy-3-phenyl 4H-chromen-4-one (7-hydroxyflavone) had the most severe effect. In addition, we further analyzed the downstream signal transduction of the ADP receptor, including the release of calcium ions and the regulation of cAMP, which were inhibited by the six coumarin derivatives selected in this study. These results suggest that coumarin derivatives inhibit coagulation by inhibiting the synthesis of coagulation factors and they may also inhibit platelet aggregation.
Asunto(s)
Activación Plaquetaria , Agregación Plaquetaria , Adenosina Difosfato/farmacología , Plaquetas , Cumarinas/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/farmacologíaRESUMEN
Tazarotene-induced gene 1 (TIG1) is considered to be a tumor suppressor gene that is highly expressed in normal or well-differentiated colon tissues, while downregulation of TIG1 expression occurs in poorly differentiated colorectal cancer (CRC) tissues. However, it is still unclear how TIG1 regulates the tumorigenesis of CRC. Polo-like kinases (Plks) are believed to play an important role in regulating the cell cycle. The performance of PLK2 in CRC is negatively correlated with the differentiation status of CRC tissues. Here, we found that PLK2 can induce the growth of CRC cells and that TIG1 can prevent PLK2 from promoting the proliferation of CRC cells. We also found that the expression of PLK2 in CRC cells was associated with low levels of Fbxw7 protein and increased expression of cyclin E1. When TIG1 was coexpressed with PLK2, the changes in Fbxw7/cyclin E1 levels induced by PLK2 were reversed. In contrast, silencing TIG1 promoted the proliferation of CRC, and when PLK2 was also silenced, the proliferation of CRC cells induced by TIG1 silencing was significantly inhibited. The above research results suggest that TIG1 can regulate the tumorigenesis of CRC by regulating the activity of PLK2.
Asunto(s)
Neoplasias Colorrectales/genética , Proteínas de la Membrana/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , División Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/metabolismo , Ciclina E/genética , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Silenciador del Gen/fisiología , Células HCT116 , Humanos , Proteínas de la Membrana/metabolismo , Proteínas Oncogénicas/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Quinasa Tipo Polo 1RESUMEN
Introduction: Acute lung injury (ALI) has a great impact and a high mortality rate in intensive care units (ICUs). Excessive air may enter the lungs, causing pulmonary air embolism (AE)-induced ALI. Some invasive iatrogenic procedures cause pulmonary AE-induced ALI, with the presentation of severe inflammatory reactions, hypoxia, and pulmonary hypertension. Pulmonary surfactants are vital in the lungs to reduce the surface tension and inflammation. Nonionic surfactants (NIS) are a kind of surfactants without electric charge on their hydrophilic parts. Studies on NIS in AE-induced ALI are limited. We aimed to study the protective effects and mechanisms of NIS in AE-induced ALI. Materials and methods: Five different groups (n = 6 in each group) were created: sham, AE, AE + NIS pretreatment (0.5 mg/kg), AE + NIS pretreatment (1 mg/kg), and AE + post-AE NIS (1 mg/kg). AE-induced ALI was introduced by the infusion of air via the pulmonary artery. Aerosolized NIS were administered via tracheostomy. Results: Pulmonary AE-induced ALI showed destruction of the alveolar cell integrity with increased pulmonary microvascular permeability, pulmonary vascular resistance, pulmonary edema, and lung inflammation. The activation of nuclear factor-κB (NF-κB) increased the expression of pro-inflammatory cytokines, and sodium-potassium-chloride co-transporter isoform 1 (NKCC1). The pretreatment with NIS (1 mg/kg) prominently maintained the integrity of the epithelial lining and suppressed the expression of NF-κB, pro-inflammatory cytokines, and NKCC1, subsequently reducing AE-induced ALI. Conclusions: NIS maintained the integrity of the epithelial lining and suppressed the expression of NF-κB, pro-inflammatory cytokines, and NKCC1, thereby reducing hyperpermeability, pulmonary edema, and inflammation in ALI.
Asunto(s)
Lesión Pulmonar Aguda/prevención & control , Alveolos Pulmonares/efectos de los fármacos , Embolia Pulmonar/tratamiento farmacológico , Mucosa Respiratoria/efectos de los fármacos , Tensoactivos/administración & dosificación , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/patología , Administración por Inhalación , Aerosoles , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/patología , Masculino , FN-kappa B/metabolismo , Alveolos Pulmonares/metabolismo , Embolia Pulmonar/complicaciones , Embolia Pulmonar/patología , Ratas , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/ultraestructura , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunologíaRESUMEN
Zotarolimus is a semi-synthetic derivative of rapamycin and a novel immunosuppressive agent used to prevent graft rejection. The pharmacological pathway of zotarolimus restricts the kinase activity of the mammalian target of rapamycin (mTOR), which potentially leads to reductions in cell division, cell growth, cell proliferation, and inflammation. These pathways have a critical influence on tumorigenesis. This study aims to examine the anti-tumor effect of zotarolimus or zotarolimus combined with 5-fluorouracil (5-FU) on A549 human lung adenocarcinoma cell line implanted in BALB/c nude mice by estimating tumor growth, apoptosis expression, inflammation, and metastasis. We established A549 xenografts in nude mice, following which we randomly divided the mice into four groups: control, 5-FU (100 mg/kg/week), zotarolimus (2 mg/kg/day), and zotarolimus combined with 5-FU. Compared the results with those for control mice, we found that mice treated with zotarolimus or zotarolimus combined with 5-FU retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; decreased inflammation cytokines levels (e.g., IL-1ß, TNF-α, and IL-6); reduced inflammation-related factors such as cyclooxygenase-2 (COX-2) protein and nuclear factor-κB (NF-κB) mRNA; enhanced anti-inflammation-related factors including IL-10 and inhibitor of NF-κB kinase α (IκBα) mRNA; and inhibited metastasis-related factors such as transforming growth factor ß (TGF-ß), CD44, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). Notably, mice treated with zotarolimus combined with 5-FU had significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with the groups of mice treated with 5-FU or zotarolimus alone. The in vivo study confirmed that zotarolimus or zotarolimus combined with 5-FU could retard lung adenocarcinoma growth and inhibit tumorigenesis. Zotarolimus and 5-FU were found to have an obvious synergistic tumor-inhibiting effect on lung adenocarcinoma. Therefore, both zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents for treatment of human lung adenocarcinoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Sirolimus/análogos & derivados , Células A549 , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Citocinas/sangre , Citocinas/metabolismo , Receptores ErbB/metabolismo , Fluorouracilo/administración & dosificación , Humanos , Receptores de Hialuranos/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Ratones Endogámicos BALB C , FN-kappa B/genética , FN-kappa B/metabolismo , Sirolimus/administración & dosificación , Sirolimus/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1ß, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor ß (TGF-ß), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Animales , Apoptosis , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Fluorouracilo/administración & dosificación , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Background and objectives: Tumor progression and the immune response are intricately linked. Additionally, the presence of macrophages in the microenvironment is essential for carcinogenesis, but regulation of the polarization of M1- and M2-like macrophages and their role in metastasis remain unclear. Based on previous studies, both reactive oxygen species (ROS) and the endoplasmic reticulum (ER) are emerging as key players in macrophage polarization. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, there is limited knowledge regarding how they affect the macrophage-dependent innate host defense. Materials and methods: We detected the levels of ROS, the ability of chemotaxis, the expressions of markers of M1-/M2-like macrophages in RAW264.7 in presence of T2- and T2C-conditioned medium. Results: The results of this study indicated that ROS levels were decreased in RAW 264.7 cells when cultured with T2C-conditioned medium, while there was an improvement in chemotaxis abilities. We also found that the M2-like macrophages were characterized by an elongated shape in RAW 264.7 cells cultured in T2C-conditioned medium, which had increased CD206 expression but decreased expression of CD86 and inducible nitric oxide synthase. Suppression of ER stress shifted polarized M1-like macrophages toward an M2-like phenotype in RAW 264.7 cells cultured in T2C-conditioned medium. Conclusions: Taken together, we conclude that the polarization of macrophages is associated with the alteration of cell shape, ROS accumulation, and ER stress.
Asunto(s)
Activación de Macrófagos , Neoplasias , Animales , Macrófagos , Ratones , Células RAW 264.7 , Especies Reactivas de Oxígeno , Microambiente TumoralRESUMEN
Hepatitis B virus X protein (HBx) and hepatic stellate cells (HSCs) are critical for liver fibrosis development. Anti-fibrosis occurs via reversion to quiescent-type HSCs or clearance of HSCs via apoptosis or ferroptosis. We aimed to elucidate the role of chrysophanol in rat HSC-T6 cells expressing HBx and investigate whether chrysophanol (isolated from Rheum palmatum rhizomes) influences cell death via ferroptosis in vitro. Analysis of lipid reactive oxygen species (ROS), Bip, CHOP, p-IRE1α, GPX4, SLC7A11, α-SMA, and CTGF showed that chrysophanol attenuated HBx-repressed cell death. Chrysophanol can impair HBx-induced activation of HSCs via endoplasmic reticulum stress (ER stress) and ferroptosis-dependent and GPX4-independent pathways.
Asunto(s)
Antraquinonas/farmacología , Antraquinonas/uso terapéutico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Células Estrelladas Hepáticas/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Fitoterapia , Transactivadores/efectos adversos , Proteínas Reguladoras y Accesorias Virales/efectos adversos , Animales , Antraquinonas/aislamiento & purificación , Línea Celular , Fibrosis , Células Estrelladas Hepáticas/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Descurainia sophia Webb ex Prantl has been used in traditional medicine globally. It has been shown that Descurainia sophia, together with many other bioactive compounds, can modulate the biological functions of various genes. We have viewed the clinical benefits and mechanisms of action of Descurainia sophia associated with its current uses and outlined potential further applications. There are many studies documenting its numerous clinical effects in cancer, respiratory, gastrointestinal, and cardiac systems. Further, Descurainia sophia has been shown to exhibit anti-inflammatory, anti-oxidative, and anthelmintic activities. The clinical studies did not indicate any significant adverse effects of Descurainia sophia, demonstrating that it is a safe and effective herbal medicine. However, more clinical studies demonstrating the therapeutic effects of Descurainia sophia are still warranted.
Asunto(s)
Brassicaceae/química , Medicina Tradicional/métodos , Fitoterapia/métodos , Extractos Vegetales/farmacología , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Enfermedades Gastrointestinales/terapia , Cardiopatías/terapia , Humanos , Neoplasias/terapia , Extractos Vegetales/uso terapéutico , Enfermedades Respiratorias/terapia , Semillas/químicaRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a condition involving several molecular mechanisms related to the intestinal microbiota for its development. Intestinal fatty acid-binding protein (I-FABP) is a sensitive marker to study enterocyte damage. A prebiotic is a non-digestible food ingredient that improves host health by selectively stimulating the growth and/or activities of bacteria in the colon. We aimed to clarify the currently described effects of prebiotics in the prevention and management of T2DM. METHODS: In this case-control study, we chose 68 participants with T2DM and 52 healthy participants. Both groups were further divided based on consumption of prebiotics. Forty participants with T2DM consumed prebiotics, and 28 did not; 30 healthy volunteers consumed prebiotics, and 22 did not. We used the analysis of variance to compare the inflammation levels between the case and control groups. Multiple linear regression was performed for the significantly correlated groups to estimate the influence of prebiotics on inflammation level. RESULTS: Age was a significant factor for difference in I-FABP levels (standardized coefficient: 0.06; P = .047). The analysis of eating habits showed that vegetarian diets produced lower I-FABP levels than non-vegetarian diets (standardized coefficient: -2.55; P = .022). Results showed that patients with T2DM who consumed prebiotics expressed lower I-FABP levels, reflecting an improvement in inflammation level, than the healthy volunteers who did not consume prebiotics (standardized coefficient: -3.20; P = .019). CONCLUSIONS: For patients with T2DM, prebiotics supplemented produced no significant impact on serum I-FABP levels.
Asunto(s)
Diabetes Mellitus Tipo 2 , Dieta/estadística & datos numéricos , Proteínas de Unión a Ácidos Grasos/sangre , Prebióticos , Adulto , Anciano , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oligosacáridos , Estudios RetrospectivosRESUMEN
Background: Cholesterol efflux efficiency, reactive oxygen species, and inflammation are closely related to cardiovascular diseases. Our aim was to investigate the effect of propofol on cholesterol-loaded rat aortic endothelial cells after high-density lipoprotein treatment in vitro. Methods and Results: The results showed that propofol promoted cholesterol efflux and ameliorated inflammation and reactive oxygen species overproduction according to the analysis of p65 nuclear translocation and a 2',7'-dichlorofluorescin diacetate assay, respectively. Conclusions: These results provide a possible explanation for the anti-inflammatory, antioxidant, and cholesterol efflux-promoting effects of propofol on rat aortic endothelial cells after incubation with high-density lipoprotein.