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Liriodendron chinense has been widely utilized in traditional Chinese medicine to treat dispelling wind and dampness and used for alleviating cough and diminishing inflammation. However, the antioxidant, antimicrobial, and anti-inflammatory effects of L. chinense leaves and the key active constituents remained elusive. So, we conducted some experiments to support the application of L. chinense in traditional Chinese medicine by investigating the antioxidant, antibacterial, and anti-inflammatory abilities, and to identify the potential key constituents responsible for the activities. The ethanol extract of L. chinense leaves (LCLE) was isolated and extracted, and assays measuring ferric reducing antioxidant power, total reducing power, DPPHâ¢, ABTSâ¢+, and â¢OH were used to assess its in vitro antioxidant capacities. Antimicrobial activities of LCLE were investigated by minimal inhibitory levels, minimum antibacterial concentrations, disc diffusion test, and scanning electron microscope examination. Further, in vivo experiments including macro indicators examination, histopathological examination, and biochemical parameters measurement were conducted to investigate the effects of LCLE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LCLE was further isolated and purified through column chromatography, and LPS-induced RAW264.7 cells were constructed to assess the diminished inflammation potential of the identified chemical composites. ABTSâ¢+ and â¢OH radicals were extensively neutralized by the LCLE treatment. LCLE administration also presented broad-spectrum antimicrobial properties, especially against Staphylococcus epidermidis by disrupting cell walls. LPS-induced ALI in mice was significantly ameliorated by LCLE intervention, as evidenced by the histological changes in the lung and liver tissues as well as the reductions of nitric oxide (NO), TNF-α, and IL-6 production. Furthermore, three novel compounds including fragransin B2, liriodendritol, and rhamnocitrin were isolated, purified, and identified from LCLE. These three compounds exhibited differential regulation on NO accumulation and IL-10, IL-1ß, IL-6, TNF-α, COX-2, and iNOS mRNA expression in RAW264.7 cells induced by LPS. Fragransin B2 was more effective in inhibiting TNF-α mRNA expression, while rhamnocitrin was more powerful in inhibiting IL-6 mRNA expression. LCLE had significant antioxidant, antimicrobial, and anti-inflammatory effects. Fragransin B2, liriodendritol, and rhamnocitrin were probably key active constituents of LCLE, which might act synergistically to treat inflammatory-related disorders. This study provided a valuable view of the healing potential of L. chinense leaves in curing inflammatory diseases.
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Six new dimeric 2-(2-phenylethyl)chromones (1-6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1-6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8'') of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 µM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 µM.
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Antiinflamatorios , Monofenol Monooxigenasa , Óxido Nítrico , Thymelaeaceae , Madera , Células RAW 264.7 , Animales , Thymelaeaceae/química , Ratones , Estructura Molecular , Madera/química , Óxido Nítrico/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Filipinas , Cromonas/aislamiento & purificación , Cromonas/farmacología , Cromonas/química , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , FlavonoidesRESUMEN
The diagnosis of cancer is typically based on histopathological sections or biopsies on glass slides. Artificial intelligence (AI) approaches have greatly enhanced our ability to extract quantitative information from digital histopathology images as a rapid growth in oncology data. Gynecological cancers are major diseases affecting women's health worldwide. They are characterized by high mortality and poor prognosis, underscoring the critical importance of early detection, treatment, and identification of prognostic factors. This review highlights the various clinical applications of AI in gynecological cancers using digitized histopathology slides. Particularly, deep learning models have shown promise in accurately diagnosing, classifying histopathological subtypes, and predicting treatment response and prognosis. Furthermore, the integration with transcriptomics, proteomics, and other multi-omics techniques can provide valuable insights into the molecular features of diseases. Despite the considerable potential of AI, substantial challenges remain. Further improvements in data acquisition and model optimization are required, and the exploration of broader clinical applications, such as the biomarker discovery, need to be explored.
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BACKGROUND: Gastric cancer (GC) is one of the most common cancers worldwide. Morbidity and mortality have increased in recent years, making it an urgent issue to address. Laparoscopic radical surgery (LRS) is a crucial method for treating patients with GC; However, its influence on tumor markers is still under investigation. AIM: To determine the effects of LRS on patients with GC and their serum tumor markers. METHODS: The data of 194 patients treated at Chongqing University Cancer Hospital between January 2018 and January 2019 were retrospectively analyzed. Patients who underwent traditional open surgery and LRS were assigned to the control (n = 90) and observation groups (n = 104), respectively. Independent sample t-tests and χ2 tests were used to compare the two groups based on clinical efficacy, changes in tumor marker levels after treatment, clinical data, and the incidence of postoperative complications. To investigate the association between tumor marker levels and clinical efficacy in patients with GC, three-year recurrence rates in the two groups were compared. RESULTS: Patients in the observation group had a shorter duration of operation, less intraoperative blood loss, an earlier postoperative eating time, and a shorter hospital stay than those in the control group (P < 0.05). No significant difference was observed between the two groups regarding the number of lymph node dissections (P > 0.05). After treatment, the overall response rate in the control group was significantly lower than that in the observation group (P = 0.001). Furthermore, after treatment, the levels of carbohydrate antigen 19-9, cancer antigen 72-4, carcinoembryonic antigen, and cancer antigen 125 decreased significantly. The observation group also exhibited a significantly lower incidence rate of postoperative complications compared to the control group (P < 0.001). Additionally, the two groups did not significantly differ in terms of three-year survival and recurrence rates (P > 0.05). CONCLUSION: LRS effectively treats early gastric cancer by reducing intraoperative bleeding, length of hospital stays, and postoperative complications. It also significantly lowers tumor marker levels, thus improving the short-term prognosis of the disease.
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Environmental stress at high altitudes drives the development of distinct adaptive mechanisms in plants. However, studies exploring the genetic adaptive mechanisms of high-altitude plant species are scarce. In the present study, we explored the high-altitude adaptive mechanisms of plants in the Himalayas through whole-genome resequencing. We studied two widespread members of the Himalayan endemic alpine genus Roscoea (Zingiberaceae): R. alpina (a selfing species) and R. purpurea (an outcrossing species). These species are distributed widely in the Himalayas with distinct non-overlapping altitude distributions; R. alpina is distributed at higher elevations, and R. purpurea occurs at lower elevations. Compared to R. purpurea, R. alpina exhibited higher levels of linkage disequilibrium, Tajima's D, and inbreeding coefficient, as well as lower recombination rates and genetic diversity. Approximately 96.3% of the genes in the reference genome underwent significant genetic divergence (FST ≥ 0.25). We reported 58 completely divergent genes (FST = 1), of which only 17 genes were annotated with specific functions. The functions of these genes were primarily related to adapting to the specific characteristics of high-altitude environments. Our findings provide novel insights into how evolutionary innovations promote the adaptation of mountain alpine species to high altitudes and harsh habitats.
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Altitud , Zingiberaceae , Himalayas , Genómica , Evolución Biológica , Adaptación Fisiológica/genéticaRESUMEN
BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.
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Neoplasias de la Mama , Animales , Ratones , Humanos , Femenino , Neoplasias de la Mama/patología , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Ácidos Grasos , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfohidrolasa PTEN/genética , Proliferación Celular , Regulación Neoplásica de la Expresión GénicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Obesity has become a public burden worldwide due to its booming incidence and various complications, and browning of white adipose tissue (WAT) is recognized as a hopeful strategy to combat it. Blossom of Citrus aurantium L. var. amara Engl. (CAVA) is a popular folk medicine and dietary supplement used for relieving dyspepsia, which is recorded in the Chinese Materia Medica. Our previous study showed that blossom of CAVA had anti-obesity potential, while its role in browning of WAT was still unclear. AIM OF THE STUDY: This study aimed to characterize the constituents in flavonoids from blossom of CAVA (CAVAF) and to clarify the anti-obesity capacities especially the effects on browning of WAT. MATERIALS AND METHODS: Gradient ethanol eluents from blossom of CAVA were obtained by AB-8 macroporous resin. 3T3-L1 cells and pancreatic lipase inhibition assay were employed to investigate the potential anti-obesity effects in vitro. HPLC and UPLC/MS assays were performed to characterize the chemical profiles of different eluents. Network pharmacology and molecular docking assays were used to reveal potential anti-obesity targets. Furthermore, high-fat diet (HFD)-induced mice were constructed to explore the anti-obesity actions and mechanisms in vivo. RESULTS: 30% ethanol eluents with high flavonoid content and great inhibition on proliferation of 3T3-L1 preadipocytes and pancreatic lipase activity were regarded as CAVAF. 19 compounds were identified in CAVAF. Network pharmacology analysis demonstrated that AMPK and PPARα were potential targets for CAVAF in alleviating obesity. Animal studies demonstrated that CAVAF intervention significantly decreased the body weight, WAT weight, serum TG, TC and LDL-C levels in HFD-fed obese mice. HFD-induced insulin resistance and morphological changes in WAT and brown adipose tissue were also markedly attenuated by CAVAF treatment. CAVAF supplementation potently inhibited iWAT inflammation by regulating IL-6, IL-1ß, TNF-α and IL-10 mRNA expression in iWAT of mice. Furthermore, the gene expression levels of thermogenic markers including Cyto C, ATP synthesis, Cidea, Cox8b and especially UCP1 in iWAT of mice were significantly up-regulated by CAVAF administration. CAVAF intervention also markedly increased the expression levels of PRDM16, PGC-1α, SIRT1, AMPK-α1, PPARα and PPARγ mRNA in iWAT of mice. CONCLUSION: CAVAF treatment significantly promoted browning of WAT in HFD-fed mice. These results suggested that flavonoid extracts from blossom of CAVA were probably promising candidates for the treatment of obesity.
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Citrus , Flavonoides , Ratones , Animales , Flavonoides/farmacología , Flavonoides/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Proteínas Quinasas Activadas por AMP/metabolismo , Simulación del Acoplamiento Molecular , PPAR alfa , Tejido Adiposo Blanco , Obesidad/metabolismo , Etanol/farmacología , Citrus/química , ARN Mensajero , Lipasa , Ratones Endogámicos C57BLRESUMEN
This study was sought to investigate the chemical composition and antibacterial and antiulcerative colitis (UC) effects of essential oil from Pruni Semen (PSEO). A GC-MS assay showed that the major compounds in PSEO were products of amygdalin hydrolysis, which possessed great antibacterial and anti-inflammatory potential. In vitro antibacterial experiments demonstrated that PSEO treatment inhibited activity of four kinds of intestinal pathogens probably by disrupting the cell wall. Further in vivo studies showed that PSEO administration significantly improved physiological indexes, attenuated histopathological characteristics, and inhibited proinflammatory cytokine production in dextran sulfate sodium (DSS)-induced UC mice. Network pharmacology and molecular docking results predicted that PSEO might prevent UC via regulating the PI3K/AKT pathway. Western blotting and immunofluorescence assays were further conducted for verification, and the results evidenced that PSEO intervention significantly regulated the PI3K/AKT pathway and the expression of its downstream proteins in DSS-induced mice. PSEO might provide a new dietary strategy for UC treatment.
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Colitis Ulcerosa , Colitis , Aceites Volátiles , Ratones , Animales , Aceites Volátiles/química , Proteínas Proto-Oncogénicas c-akt/genética , Semen/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Simulación del Acoplamiento Molecular , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Antibacterianos/farmacología , Colitis Ulcerosa/inducido químicamente , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Colon/metabolismoRESUMEN
In this study, analysis of the chemical constituents and bioactivities of the unpolar fractions [petroleum ether (PE) and chloroform (C)] of fruits and leaves of Alpinia oxyphylla Miq. were carried out, as well as the bioactivities of the main compounds nootkatone and valencene. From PE and C fractions of the fruits, and PE fraction of the leaves, 95.80%, 59.30%, and 82.11% of the chemical constituents respectively were identified by GC-MS. Among these identified compounds, nootkatone was the main compound in all of three fractions, while valencene was the second main compound in the PE fractions of the fruits and leaves. The bioactivities results showed that all of the fractions and the major compound nootkatone showed tyrosinase inhibitory, as well as inhibitory effect on NO production in LPS-stimulated RAW264.7 cells. While valencene only presented inhibitory activity on NO production in RAW264.7 cells. The critical genes involved in nootkatone biosynthesis in A. oxyphylla were identified from the public transcriptome datasets, and protein sequences were preliminarily analyzed. Our studies develop the usage of the unpolar fractions of A. oxyphylla, especially its leaves as the waste during its production, and meanwhile provide the gene resources for nootkatone biosynthesis.
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Alpinia , Sesquiterpenos Policíclicos , Sesquiterpenos , Alpinia/química , Extractos Vegetales/farmacologíaRESUMEN
Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.
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Carcinoma Endometrioide , Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/genética , Neoplasias Ováricas/metabolismo , Proteómica , Carcinoma Endometrioide/metabolismo , Transducción de Señal , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proteínas de la MembranaRESUMEN
This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg~(-1)·d~(-1)), a probiotics group(0.39 g·kg~(-1)·d~(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg~(-1)·d~(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg~(-1)·d~(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg~(-1)·d~(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg~(-1)·d~(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aß_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1ß(IL-1ß) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aß_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1ß in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.
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Enfermedad de Alzheimer , Fármacos Neuroprotectores , Humanos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Sirtuina 1/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Enfermedades Neuroinflamatorias , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptor Toll-Like 1/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , HipocampoRESUMEN
Neuronal synchronization at gamma frequency (30-100 Hz: γ) is impaired in early-stage Alzheimer's disease (AD) patients and AD models. Oligomeric Aß1-42 caused a concentration-dependent reduction of γ-oscillation strength and regularity while increasing its frequency. The mTOR1 inhibitor rapamycin prevented the Aß1-42-induced suppression of γ-oscillations, whereas the mTOR activator leucine mimicked the Aß1-42-induced suppression. Activation of the downstream kinase S6K1, but not inhibition of eIF4E, was required for the Aß1-42-induced suppression. The involvement of the mTOR/S6K1 signaling in the Aß1-42-induced suppression was confirmed in Aß-overexpressing APP/PS1 mice, where inhibiting mTOR or S6K1 restored degraded γ-oscillations. To assess the network changes that may underlie the mTOR/S6K1 mediated γ-oscillation impairment in AD, we tested the effect of Aß1-42 on IPSCs and EPSCs recorded in pyramidal neurons. Aß1-42 reduced EPSC amplitude and frequency and IPSC frequency, which could be prevented by inhibiting mTOR or S6K1. These experiments indicate that in early AD, oligomer Aß1-42 impairs γ-oscillations by reducing inhibitory interneuron activity by activating the mTOR/S6K1 signaling pathway, which may contribute to early cognitive decline and provides new therapeutic targets.
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Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , Adherencias Tisulares/tratamiento farmacológico , Adherencias Tisulares/prevención & control , Desarrollo Industrial , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Okadaic acid (OA), a lipophilic phycotoxin distributed worldwide, causes diarrheic shellfish poisoning and even leads to tumor formation. Currently, the consumption of contaminated seafood is the most likely cause of chronic OA exposure, but there is a serious lack of relevant data. Here, the Sprague-Dawley rats were exposure to OA by oral administration at 100 µg/kg body weight, and the tissues were collected and analyzed to assess the effect of subchronic OA exposure. The results showed that subchronic OA administration disturbed colonic mucosal integrity and induced colitis. The colonic tight junction proteins were disrupted and the cell cycle of colonic epithelial cells was accelerated. It is inferred that disruption of the colonic tight junction proteins might be related to the development of chronic diarrhea by affecting water and ion transport. Moreover, the accelerated proliferation of colonic epithelial cells indicated that subchronic OA exposure might promote the restitution process of gut barrier or induce tumor promoter activity in rat colon.
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Carcinógenos , Proteínas de Uniones Estrechas , Ratas , Animales , Ácido Ocadaico/toxicidad , Proteínas de Uniones Estrechas/metabolismo , Ratas Sprague-Dawley , Colon/metabolismoRESUMEN
Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.
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Diabetes Mellitus Experimental , FN-kappa B , Ratones , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Aloxano , Sinefrina , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Ácido Úrico , Estrés Oxidativo , Antioxidantes/farmacología , Inflamación/tratamiento farmacológico , Glutatión/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Circadian dysfunction is a common non-motor symptom in Parkinson's disease (PD). The potential influence of aggravated α-synuclein (SNCA) on circadian disruption remains unclear. SNCAA53T-overexpressing transgenic mice (SNCAA53T mice) and wild-type (WT) littermates were used in this study. The energy metabolism cage test showed differences in 24-h activity pattern between SNCAA53T and WT mice. When compared with the age-matched littermates, brain and muscle ARNT-like 1 (BMAL1) was downregulated in SNCAA53T mice. BMAL1 was downregulated in PC12 cells overexpressing SNCA. Degradation of BMAL1 protein remained unchanged after overexpression of SNCA, while its mRNA level decreased. miRNA (miR)-155 was upregulated by overexpression of SNCA, and downregulation of BMAL1 was partially reversed by transfection with miR-155 inhibitor. Our findings demonstrated that overexpression of SNCA induced biorhythm disruption and downregulated BMAL1 expression through decreasing stability of BMAL1 mRNA via miR-155.
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MicroARNs , Enfermedad de Parkinson , Ratas , Ratones , Animales , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Enfermedad de Parkinson/metabolismo , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Encéfalo/metabolismo , Ratones Transgénicos , Músculos , Ritmo Circadiano/genética , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
BACKGROUND: Deep brain stimulation (DBS) is recommended for the treatment of advanced Parkinson's disease (PD), though individual reactions may be different. There are currently no clinically available biomarkers for predicting the responses of PD patients to DBS before surgery. This study aimed to determine serum biomarkers to predict DBS responses in PD. METHODS: We profiled differentially expressed proteins (DEPs) in serum samples and identified potential biomarkers to predict the therapeutic responses to DBS in PD patients. Ten serum samples were selected from PD patients to identify DEPs via mass spectrometry proteomics; these were then verified by enzyme-linked immunosorbent assay in another 21 serum samples of PD patients. RESULTS: The present study identified 14 DEPs (10 downregulated and four upregulated DEPs) with significantly different levels between non-responders and responders. Most of the DEPs were related to amino acid metabolism and protein modification pathways. Bleomycin hydrolase (BLMH) and creatine kinase M-type (CKM) were found to be significantly downregulated in the responders. Additionally, subsequent logistic regression and receiver operating characteristic analyses were performed to determine the diagnostic performance of candidate proteins. CONCLUSIONS: The identified DEPs show potential as biomarkers for the accurate evaluation of DBS therapeutic responses before surgery. Furthermore, assessment of serum BLMH and CKM may be particularly useful for predicting the therapeutic responses to DBS in PD patients.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/terapia , Estimulación Encefálica Profunda/métodos , ProteómicaRESUMEN
Background: Given the benzimidazole derivatives have anti-ovarian cancer effects, the authors aimed to determine whether benzimidazole-2-substituted pyridine and phenyl propenone derivatives exert anti-ovarian cancer activity. Materials & methods: 21 derivatives were synthesized and assayed for their antiproliferative activities. Western blotting in A2780 cells was used to detect the effects of compound A-6 on apoptosis-related proteins. Invasion, migration and apoptosis were assayed in SKOV3 cells treated with A-6. The in vivo activity was also examined. Results: A-6 could inhibit proliferation, invasion and migration and induce apoptosis in SKOV3 cells. Additionally, A-6 had potent inhibitory activity in a xenograft mouse model. Conclusion: A-6 shows potent efficacy in the treatment of ovarian cancer and may be a potential antitumor agent.
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Antineoplásicos , Neoplasias Ováricas , Humanos , Animales , Ratones , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Bencimidazoles/farmacología , Piridinas/farmacología , Piridinas/uso terapéutico , Proliferación CelularRESUMEN
OBJECTIVES: To study the genetic polymorphism and population genetic parameters of 16 X-STR loci in Xinjiang Uygur population. METHODS: The Goldeneye® DNA identification system 17X was used to amplify 16 X-STR loci in 502 unrelated individuals (251 females and 251 males). The amplified products were detected by 3130xl genetic analyzer. Allele frequencies and population genetic parameters were analyzed statistically. The genetic distances between Uygur and other 8 populations were calculated. Multidimensional scaling and phylogenetic tree were constructed based on genetic distance. RESULTS: In the 16 X-STR loci, a total of 67 alleles were detected in 502 Xinjiang Uygur unrelated individuals. The allele frequencies ranged from 0.001 3 to 0.572 4. PIC ranged from 0.568 8 to 0.855 3. The cumulative discrimination power in females and males were 0.999 999 999 999 999 and 0.999 999 999 743 071, respectively. The cumulative mean paternity exclusion chance in trios and in duos were 0.999 999 997 791 859 and 0.999 998 989 000 730, respectively. The genetic distance between Uygur population and Kazakh population was closer, and the genetic distance between Uygur and Han population was farther. CONCLUSIONS: The 16 X-STR loci are highly polymorphic and suitable for identification in Uygur population, which can provide a powerful supplement for the study of individual identification, paternity identification and population genetics.