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This study aimed to employed the effects of five thermal processing methods, namely steaming (SM), boiling (BO), frying (FY), roasting (RO), and vacuum sealing (SV), on the sensory, physicochemical properties, and microbial composition of grass carp meat during refrigerated storage, alongside unheated raw meat (RW) as control. The results showed that thermal treatment improved the sensory quality and shelf life of refrigerated grass carp meat, and their shelf life was RW < BO

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BACKGROUND: Lingguizhugan (LGZG) decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet (HFD)-induced insulin resistance (IR) in animal studies. AIM: To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism. METHODS: To establish an IR rat model, a 12-wk HFD was administered, followed by a 4-wk treatment with LGZG. The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests. Using a targeted meta-bolomics platform to analyze changes in serum metabolites, quantitative real-time PCR (qRT-PCR) was used to assess the gene expression of the ribosomal protein S6 kinase beta 1 (S6K1). RESULTS: In IR rats, LGZG decreased body weight and indices of hepatic steatosis. It effectively controlled blood glucose and food intake while protecting islet cells. Metabolite analysis revealed significant differences between the HFD and HFD-LGZG groups. LGZG intervention reduced branched-chain amino acid levels. Levels of IR-related metabolites such as tryptophan, alanine, taurine, and asparagine decreased significantly. IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression, as shown by qRT-PCR. CONCLUSIONS: Our study strongly suggests that LGZG decoction reduces HFD-induced IR. LGZG may activate S6K1 via metabolic pathways. These findings lay the groundwork for the potential of LGZG as an IR treatment.

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For the efficient detection of Hg2+ and ClO-, a double-analyte-responsive fluorescent probe PTB was successfully synthesized by combining N-butyl-3-formyl phenothiazine with hydrazine benzothiazole, and designing a specific reaction site for recognizing two analytes (Hg2+ and ClO-) in a compound. It was shown that probe PTB successfully formed a stable complex with Hg2+ in the coordination ratio of 2:1 by using the strong sulfur affinity of Hg2+, which resulted in a remarkable "turn-off" effect, with a quenching efficiency of 92.5% and four reversible cycles of Hg2+ fluorescence detection. For the fluorescence detection of Hg2+, the response time is fast (≤ 2 min) and the detection limit is low (7.8 nM), showing extremely high sensitivity, and the performance is obviously better than that of the reported fluorescent probes for detecting Hg2+. In particular, probe PTB has low toxicity and good biocompatibility, and has been successfully used for imaging of Hg2+ in living cells. Moreover, probe PTB uses thioether bond and carbon-nitrogen double bond as reaction sites to detect ClO-, which has large Stokes Shift (149 nm), good selectivity, high quenching efficiency (96.5%) and fast time response (about 10 s), and successfully detects ClO- in actual water samples. The dual functional fluorescent probe PTB is sensitive for Hg2+ and ClO-. It has been successfully used for making pH fluorescent test paper and imaging detection of exogenous Hg2+ in VSMC cells with low toxicity.

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In view of the superior chemical activity of selenoether bond (-Se-) and the excellent optical properties of naphthimide, a novel fluorescent probe (NapSe) with near-rectangular structure, which contains double naphthimide fluorophores linked by selenoether bond, is designed for specific fluorescence detection of hydrogen sulfide (H2S). NapSe has excellent optical properties: super large Stokes Shift (190 nm) and good stability in a wide pH range. The selectivity of NapSe fluorescence detection of H2S is high, and displays excellent "turn-on" phenomenon and strong anti-interference. And the fluorescence intensity increased obviously, reaching 42 times. The time response of probe NapSe is very rapid (3 min) compared with other fluorescence probes that respond to H2S. It shows high sensitivity by calculating the detection limit (LOD) as low as 5.4 µM. Notably, the identification of H2S by probe NapSe has been successfully applied to the detection of test paper and the detection of exogenous and endogenous fluorescence imaging of MCF-7 breast cancer cells.

Asunto(s)

Colorantes Fluorescentes , Sulfuro de Hidrógeno , Humanos , Colorantes Fluorescentes/química , Células MCF-7 , Imagen Óptica , Espectrometría de Fluorescencia , Células HeLa

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The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1ß), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1ß, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.

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Síndrome de Dificultad Respiratoria , Sepsis , Humanos , Farmacología en Red , Factor A de Crecimiento Endotelial Vascular , FN-kappa B , Interleucina-6 , Lipopolisacáridos , Simulación del Acoplamiento Molecular , Factor de Necrosis Tumoral alfa , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/genética , Proteínas NLR

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On the basis of classical Schiff base reaction, two novel and efficient fluorescent probes (DQNS, DQNS1) were designed and synthesized by introducing Schiff base structure into dis-quinolinone unit for structural modification, which can be used to detect Al3+ and ClO-. Because the power supply capacity of H is weaker than that of methoxy, DQNS shows better optical performance: a large Stokes Shift (132 nm), identify Al3+ and ClO- with high sensitivity and selectivity, low detection limit (29.8 nM and 25 nM) and fast response time (10 min and 10 s). Through the working curve and NMR titration experiment, the recognition mechanism of Al3+ and ClO- (PET and ICT) probes are confirmed. Meanwhile, it is speculated that the probe has continuity for the detection of Al3+ and ClO-. Furthermore, DQNS detection of Al3+ and ClO- was applied to real water samples and living cell imaging.

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Colorantes Fluorescentes , Bases de Schiff , Colorantes Fluorescentes/química , Bases de Schiff/química , Imagen Óptica/métodos , Ácido Hipocloroso/química

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Xenon binding represents a formidable challenge, and efficient hosts remain rare. Here we report our findings that while enantiomeric bis(urea)-bis(thiourea) macrocycles form exclusive homochiral dimeric assemblies, xenon is able to overcome the narcissism and induces an otherwise-nonobservable heterochiral assembly as its preferred host. An experimental approach and fitting model were developed to obtain binding constants associated with the invisible assembly species. The determined xenon binding affinity with the heterochiral capsule reaches 1600 M-1, which is 15 times higher than that with the homochiral capsule and represents the highest record for an assembled host. The origin of the large difference in xenon affinity between the two subtle diastereotopic assemblies was revealed by single-crystal analysis. In the heterochiral capsule with S4 symmetry, the xenon atom is more tightly enclosed by van der Waals surroundings of the four thiourea groups arranged in a spherical cross-array, superior to the antiparallel array in the homochiral capsule with D2 symmetry.

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BACKGROUND: Salivary gland cancer is a rare disease in which cancer cells form in the tissues of the salivary glands. It mostly occurs in the glands that have secretion functions, such as the parotid gland, sublingual gland and submandibular gland. This is very rare when it occurs in other nonsecreting glands. Here, we report one case of salivary gland carcinoma occurring in the thymus and discuss related diagnoses and treatment progress. CASE SUMMARY: One 33-year-old middle-aged man presented with a thymus mass without any clinical symptoms when he underwent regular physical examination. Later, the patient was admitted to the hospital for further examination. Computed tomography (CT) showed that there was a mass of 3 cm × 2.8 cm × 1.5 cm in the thymus area. The patient had no symptom of discomfort or tumor- related medical history before. After completing the preoperative examinations, it was confirmed that the patient had indications for surgery. The surgeon performed a transthoracoscope "thymectomy + pleural mucostomy" for him. During the operation, the tumor tissue was quickly frozen, and the symptomatic section showed a malignant tumor. The final pathological result suggested thymus salivary gland carcinoma- mucoepidermoid carcinoma (MEC). In the second month after surgery, we performed local area radiotherapy for the patient, with a total radiation dose of 50.4 Gy/28Fx. After 12 mo of surgery, the patient underwent positron emission tomography-CT examination, which indicated that there was no sign of tumor recurrence or metastasis. After 16 mo of operation, CT scan re-examination showed that there was no sign of tumor recurrence or metastasis. As of the time of publication, the patient was followed up for one and a half years. He had no sign of tumor recurrence and continued to survive. CONCLUSION: The incidence of MEC in the thymus is low, and its diagnosis needs to be combined with clinical features and imaging methods. Histopathological analysis plays a key role in the diagnosis of the disease. Patients with early-stage disease have a good prognosis and long survival period. In contrast, patients with advanced-stage disease have a poor prognosis and short survival period. Combining radiotherapy and chemotherapy in inoperable patients may prolong survival.

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BACKGROUND: Paraquat (PQ)-induced acute lung injury (ALI) and pulmonary fibrosis are common diseases with high mortality but without effective antidotes in emergency medicine. Our previous study has proved that arctigenin suppressed pulmonary fibrosis induced by PQ. We wondered whether arctigenin could also have a protective effect on PQ-induced ALI. METHODS: A PQ-induced A549 cell injury model was used, and the effect of arctigenin was determined by a cell counting kit-8 (CCK-8) cell viability assay. In addition, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining assays and mitochondrial membrane potential assays were performed to evaluate the level of cell apoptosis. The generation of reactive oxygen species (ROS) was reflected by dihydroethidium (DHE) staining and a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Moreover, immunoblotting studies were used to assess the expression of mitogen-activated protein kinases (MAPKs) and p38 MAPK. RESULTS: Arctigenin attenuated PQ-induced inhibition of A549 cell viability in a dose-dependent manner. Arctigenin also significantly reduced PQ-induced A549 cell apoptosis, as reflected by the TUNEL assay and mitochondrial membrane potential assay, which may result from suppressed ROS/p38 MAPK signaling because we found that arctigenin dramatically suppressed ROS generation and p38 MAPK phosphorylation. CONCLUSION: Arctigenin could attenuate PQ-induced lung epithelial A549 cell injury in vitro by suppressing ROS/p38 MAPK-mediated cell apoptosis, and arctigenin might be considered a potential candidate drug for PQ-induced ALI.

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Spontaneous fermentation is a critical processing step that determines the taste quality of fermented mandarin fish (Siniperca chuatsi). Here, untargeted metabolomics using ultra-high-performance liquid chromatography coupled with Q Exactive tandem mass spectrometry was employed to characterize the taste-related metabolite profiles during the fermentation of mandarin fish. The results demonstrated that the taste profiles of mandarin fish at different stages of fermentation could be distinguished using an electronic tongue technique. Sixty-two metabolites, including amino acids, small peptides, fatty acids, alkaloids, and organic acids, were identified in fermented mandarin fish samples. Additional quantitative analysis of amino acids revealed glutamic acid and aspartic acid as significant contributors to the fresh flavor. Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that amino acid metabolism was the dominant pathway throughout the fermentation process. This study provides a scientific and theoretical reference for the targeted regulation of the quality of fermented mandarin fish.

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A network pharmacology-based strategy combined with molecular docking and in vitro validation was employed to investigate potential targets and molecular mechanisms of modified Liangge San(MLGS) against acute respiratory distress syndrome(ARDS). Active ingredients and corresponding targets of MLGS were screened out on the Traditional Chinese Medicines Systems Pharmacology(TCMSP) database, and the disease targets of ARDS were obtained by integrating GeneCards and DisGeNET database. The two were intersected to obtain the potential targets of MLGS against ARDS. Cytoscape 3.7.2 was used to construct a "Chinese medicine-active ingredient-target network" of MLGS and a "regulatory network of MLGS against ARDS". The protein-protein interaction(PPI) network was created on the STRING database platform, and the Metascape database was used to carry out Gene Ontology(GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Subsequently, molecular docking and in vitro experiments were performed to further verify the above findings. A total of 211 active ingredients of MLGS and 54 key targets were obtained. The GO enrichment analysis obtained 709 GO entries(P<0.05), including 457 biological processes(BP), 50 cell components(CC), and 98 molecular functions(MF), mainly involved in lipopolysaccharides, response to reactive oxygen species, and apoptosis signal pathways. KEGG pathway enrichment analysis obtained 266 pathways, mainly involved in the cancer signaling pathways, advanced glycation end-products and their receptors(AGE-RAGE) signaling pathways, fluid shear stress, atherosclerosis, proteoglycan pathway in cancer, nuclear and factor kappa B(NF-κB) signaling pathway. Molecular docking showed that the main active ingredients bound steadily with the targets. The experiments proved that MLGS inhibited the generation of reactive oxygen species and the activation of NF-κB signaling pathway, thereby reducing apoptosis. The study shows that MLGS, through its multiple active ingredients including wogonin and luteolin, can treat ARDS by intervening in various signaling pathways such as NF-κB, inhibiting the inflammatory response and oxidative stress, and reducing apoptosis.

Asunto(s)

Medicamentos Herbarios Chinos , Síndrome de Dificultad Respiratoria , Humanos , FN-kappa B , Simulación del Acoplamiento Molecular , Farmacología en Red , Especies Reactivas de Oxígeno , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China

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BACKGROUND: Disruption of alveolar endothelial barrier caused by inflammation drives the progression of septic acute lung injury (ALI). Pravastatin, an inhibitor of HMG Co-A reductase, has potent anti-inflammatory effects. In the present study, we aim to explore the beneficial role of pravastatin in sepsis-induced ALI and its related mechanisms. METHODS: A septic ALI model was established by cecal ligation and puncture (CLP) in mice. The pulmonary microvascular endothelial cells (PMVECs) were challenged with lipopolysaccharide (LPS). The pathological changes in lung tissues were examined by HE staining. The pulmonary microvascular permeability was determined by lung wet-to-dry (W/D) weight ratio and Evans blue staining. The total protein concentration in bronchoalveolar lavage fluid (BALF) was detected by BCA assay. The levels of TNF-α, IL-1ß, and IL-6 were assessed by qRT-PCR and ELISA. Apoptosis was determined by flow cytometry and TUNEL. Western blotting was performed for detection of target protein levels. The expression of VE-Cadherin in lung tissues was evaluated by immunohistochemical staining. RESULTS: Pravastatin improved survival rate, attenuated lung pathological changes and reduced pulmonary microvascular permeability in septic mice. In addition, pravastatin restrained sepsis-induced inflammatory response and apoptosis in the lung tissues and PMVECs. Moreover, pravastatin up-regulated the levels of junction proteins ZO-1, JAM-C, and VE-Cadherin. Finally, pravastatin suppressed inflammation, apoptosis and enhanced the expression of junction proteins via regulating Cav-1/eNOS signaling pathway in LPS-exposed PMVECs. CONCLUSION: Pravastatin ameliorates sepsis-induced ALI through improving alveolar endothelial barrier disruption via modulating Cav-1/eNOS pathway, which may be an effective candidate for treating septic ALI.

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Lesión Pulmonar Aguda/tratamiento farmacológico , Células Endoteliales/efectos de los fármacos , Pravastatina/farmacología , Sepsis/tratamiento farmacológico , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Permeabilidad Capilar/efectos de los fármacos , Permeabilidad Capilar/inmunología , Caveolina 1/metabolismo , Modelos Animales de Enfermedad , Células Endoteliales/inmunología , Células Endoteliales/patología , Humanos , Masculino , Ratones , Óxido Nítrico Sintasa de Tipo III/metabolismo , Pravastatina/uso terapéutico , Alveolos Pulmonares/irrigación sanguínea , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/inmunología , Alveolos Pulmonares/patología , Sepsis/complicaciones , Sepsis/inmunología , Sepsis/patología

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Phosphorus-containing flame retardants have received huge interest for improving the flame retardant behavior of epoxy resins (EP) over the past few decades. However, a satisfactory flame retardant effect requires high loading of most phosphorus-containing flame retardants, resulting in the deterioration of the thermo-mechanical properties of the flame retardant epoxy materials. To obtain the flame retardant EP with excellent comprehensive properties, a furfurylamine-derived bis-DOPO derivative (FA-bis-DOPO) was synthesized from bio-mass as a co-curing agent for the flame retardant EP. The incorporation of FA-bis-DOPO improved the mechanical strength, the storage modulus and the glass transition temperature of the flame retardant epoxy materials, owing to its stiffness and reactivity with the epoxy matrix to enhance the crosslinking density. The EP material containing 5.0 wt% of FA-bis-DOPO had an LOI of 31.0% and UL-94 V-0 rating, while the pristine EP had an LOI of 23.5% and failed in the UL-94 test, manifesting the high flame retardant efficiency of FA-bis-DOPO. Besides, the cone calorimeter results demonstrated that the PHRR, THR, and TSP values of the EP/FA-bis-DOPO-5.0 were 28.0%, 27.3%, and 9.9% lower than those of the pristine EP, respectively. The flame retardant mechanism of FA-bis-DOPO could be attributed to the combined vapor and condensed phase mechanisms which involved the interruption of the combustion chain reaction by quenching radicals and the inhibition of the transfer of pyrolytic volatile products by catalytic formation of an intact and compact char layer.

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Xenon binding has attracted interest due to the potential for xenon separation and emerging applications in magnetic resonance imaging. Compared to their covalent counterparts, assembled hosts that are able to effectively bind xenon are rare. Here, we report a tight yet soft chiral macrocycle dimeric capsule for efficient and adaptive xenon binding in both crystal form and solution. The chiral bisurea-bisthiourea macrocycle can be easily synthesized in multi-gram scale. Through assembly, the flexible macrocycles are locked in a bowl-shaped conformation and buckled to each other, wrapping up a tight, completely sealed yet adjustable cavity suitable for xenon, with a very high affinity for an assembled host. A slow-exchange process and drastic spectral changes are observed in both 1H and 129Xe NMR. With the easy synthesis, modification and reversible characteristics, we believe the robust yet adaptive assembly system may find applications in xenon sequestration and magnetic resonance imaging-based biosensing.

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The tight binding enabled by tailor-made macrocycles can be manipulated for tuning the catalysis process. In parallel to well-developed crown ether-based cation-binding catalysis, a macrocycle-enabled counteranion trapping strategy is presented for boosting highly efficient and enantioselective catalysis. A set of bis-diarylthiourea macrocycles containing two BINOL moieties were designed and synthesized. They possess a well-confined chiral cavity and strong binding affinities towards disulfonate anions. Caused by the tight binding, just 1 mol % macrocycle in combination with 1 mol % ethanedisulfonic acid can promote excellent conversion and up to 99 % ee in the Friedel-Crafts reaction of indoles with imines. The acid or the macrocycle alone do not afford any reactivity. The high catalytic efficiency and excellent stereocontrol was ascribed to large, complexation-induced acidity enhancement and tight ion-pairing facilitated by cave-like macrocyclic cavity.

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BACKGROUND: Stress-related gastric mucosal damage or ulcer remains an unsolved issue for critically ill patients. Stress ulcer prophylaxis has been part of routine intensive care, but uncertainty and controversy still exist. Co-secreted with mucins, intestinal trefoil factor (ITF) is reported to promote restitution and regeneration of intestinal mucosal epithelium, although the mechanism remains unknown. AIM: To elucidate the protective effects of ITF on gastric mucosa and explore the possible mechanisms. METHODS: We used a rat model of gastric mucosal damage induced by water immersion restraint stress and lipopolysaccharide-treated human gastric epithelial cell line to investigate the potential effects of ITF on damaged gastric mucosa both in vivo and in vitro. RESULTS: ITF promoted the proliferation and migration and inhibited necrosis of gastric mucosal epithelia in vitro. It also preserved the integrity of gastric mucosa by upregulating expressions of occludin and zonula occludens-1. In the rat model, pretreatment with ITF ameliorated the gastric mucosal epithelial damage and facilitated mucosal repair. The protective effects of ITF were confirmed to be exerted via activation of Akt signaling, and the specific inhibitor of Akt signaling LY249002 reversed the protective effects. CONCLUSION: ITF might be a promising candidate for prevention and treatment of stress-induced gastric mucosal damage, and further studies should be undertaken to verify its clinical feasibility.

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Neuropéptidos , Proteínas Proto-Oncogénicas c-akt , Animales , Mucosa Gástrica , Sustancias de Crecimiento , Humanos , Mucosa Intestinal , Proteínas Musculares , Péptidos , Ratas , Factor Trefoil-2 , Factor Trefoil-3

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The mortality rate of non-small-cell lung cancer (NSCLC) remains high worldwide. Although cisplatin-based chemotherapy may greatly enhance patient prognosis, chemotherapy resistance remains an obstacle to curing patients with NSCLC. Therefore, overcoming drug resistance is the main route to successful treatment, and combinatorial strategies may have considerable clinical value in this effort. In this study, we observed that both parthenolide (PTL) and cisplatin (DDP) inhibited the growth of NSCLC cells in a dose- and time-dependent manner. The combination of PTL and DDP presented a synergistic inhibitory effect on NSCLC at a ratio of 50:1. The combination of PTL and DDP synergistically inhibited cell migration and invasion, inhibited cell cycle progression, and induced apoptosis of A549 and PC9 cells. Bioinformatics and network pharmacology analysis indicated that PTL may primarily affect the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. After treatment with PTL and DDP either alone or in combination, Western blot analysis revealed that the proteins levels of Bax and cleaved Caspase-3 were upregulated, while p-PI3K, p-Akt, Caspase-3, and Bcl-2 proteins were downregulated. Among these alterations, the combination of PTL and DDP was found to exhibit the most significant effects. PTL might therefore be considered as a new option for combination therapy of NSCLC.

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This paper aimed to study the protective effect of ginsenoside Rg_1 on endotoxin(LPS)-induced apoptosis of lung epithelial cells and its mechanism of action. Mouse lung epithelial cells(MLE-12) were first treated with LPS. The autophagy changes and apoptosis and the relationship with concentration and time of LPS were observed. Then,the level of autophagy in MLE-12 was regulated at a specific concentration and action time of LPS,and the changes of apoptosis were observed. Secondly,ginsenoside Rg_1 and autophagy inhibitor 3-MA were added respectively at the same concentration and action time of LPS. The lung epithelial cells were grouped to observe the effect of ginsenoside Rg_1 on LPS-induced apoptosis of lung epithelial cells and its mechanism. In the animal experiment,the mice were grouped and tested by apoptosis protein,lung injury score and HE staining section to verify whether ginsenoside Rg_1 has a protective effect on LPS-induced lung injury. The results showed that apoptosis and autophagy increased as the rise of concentration after treatment with LPS for 12 h. The apoptosis increased gradually,and the autophagy increased first and then decreased over time at the LPS concentration of 25 g·L-1. The apoptosis of LPS group was higher than that of control group,and LPS+3-MA group increased further,while apoptosis decreased significantly in LPS+RAM(rapamycin,autophagy promoter) group. The autophagy increased in LPS group,decreased in LPS+3-MA group and increased in LPS+RAM group. The apoptosis of LPS group was higher than that of control group,and the apoptosis of LPS+Rg_1 group decreased. The apoptosis of LPS+Rg_1+3-MA group increased again. The autophagy of LPS group further increased after administration of ginsenoside Rg_1,but decreased after administration of 3-MA. In the in vivo experiments in mice,the apoptosis of LPS group increased significantly compared with the control group,while LPS + ginsenoside Rg_1 group decreased. Lung injury score and HE staining also conformed to the above trend. LPS can induce the apoptosis of lung epithelial cells in a time-dependent and concentration-dependent manner. The autophagy of lung epithelial cells increases with the rise of LPS concentration. At the specific concentration of LPS,autophagy increases first and then decreases after 12-16 hours. Proper increase of autophagy in lung epithelial cells within a certain period of time can reduce the apoptosis induced by LPS,while inhibition of autophagy can increase apoptosis. Ginsenoside Rg_1 has a protective effect on lung cancer epithelial cell apoptosis induced by autophagy.

Asunto(s)

Apoptosis , Autofagia , Células Epiteliales/efectos de los fármacos , Ginsenósidos/farmacología , Pulmón/citología , Animales , Células Cultivadas , Lipopolisacáridos , Ratones

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Alkaline phosphatase (ALP) is an essential enzyme and widely distributes in a variety of tissues. To date, various nanomaterial and small-molecule fluorescent probes for ALP have been constructed successfully, but the emission wavelengths of these probes are in the ultraviolet or visible range, which is not beneficial for bioimaging. Herein, a hemicyanine-based near-infrared (NIR) fluorescent probe named CyP is first synthesized and used to detect ALP activity. The characteristics of probe CyP are as follows: (1) The probe possesses a facile structure, which can be obtained by easy synthetic steps. (2) The fluorescence emission of the sensing system is at 738 nm belonging to NIR region, which is suitable for bioimaging in vivo. (3) The probe exhibits high sensitivity to ALP with 10-fold fluorescence enhancement and low detection limit (0.003 U/mL) can match the level of ALP in vivo. (4) The fluorescent change of the probe is attributed to the fact that ALP-catalyzed cleavage of the phosphate group in CyP induces the transformation of CyP (fluorescence off) into CyOH (fluorescence on), which is proved by HPLC, 31P NMR, MS, and DFT calculation. (5) The NIR fluorescent probe is applied for the detection of endogenous ALP activity in various biological samples such as cell, tissue, and living animal with satisfactory results.

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Fosfatasa Alcalina/metabolismo , Carbocianinas/química , Colorantes Fluorescentes/química , Fosfatos/metabolismo , Espectroscopía Infrarroja Corta , Animales , Células HeLa , Humanos , Límite de Detección , Hígado/metabolismo , Ratones , Microscopía Fluorescente , Fosfatos/química , Ratas

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BACKGROUND: Previous studies have shown inconsistent or even contradictory results for some risk factors associated with HIV infection among drug users, and these may be partially explained by geographical variations. METHODS: Data were collected from 11 methadone clinics in the Liangshan Yi Autonomous Prefecture from 2004 to 2012. A non-spatial logistical regression model and a geographically weighted logistic regression model were fitted to analyze the association between HIV infection and specific factors at the individual level. RESULTS: This study enrolled 6,458 patients. The prevalence of HIV infection was 25.1 %. The non-spatial model indicated that being divorced was positively associated with HIV infection. The spatial model also showed that being divorced was positively associated with HIV infection, but only for 49.4 % of individuals residing in some northern counties. The non-spatial model suggested that service sector work was negatively associated with HIV infection. However, the spatial model indicated that service work was associated with HIV infection, but only for 23.0 % of patients living in some western counties. The non-spatial model did not show that being married was associated with HIV infection in our study field, but the spatial model indicated that being married was negatively associated with HIV infection for 12.0 % of individuals living in some western counties. For other factors, the non-spatial and spatial models showed similar results. CONCLUSION: The spatial model may be useful for improving understanding of geographical heterogeneity in the relationship between HIV infection and individual factors. Spatial heterogeneity may be useful for tailoring intervention strategies for local regions, which can consequently result in a more efficient allocation of limited resources toward the control of HIV transmission.

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Consumidores de Drogas , Infecciones por VIH/epidemiología , China/epidemiología , Femenino , Geografía Médica , Infecciones por VIH/transmisión , Humanos , Masculino , Modelos Estadísticos , Prevalencia , Factores de Riesgo