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1.
Acta Psychol (Amst) ; 248: 104351, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38905949

RESUMEN

The aim of this research is to analyze the impact of mental health on the academic performance of junior and senior students studying in a university setting during the 2022-2023 academic year, in the post-COVID period. The study was conducted in Beijing, China, with the participation of 600 students, including 300 first-year students and 300 fifth-year students. DASS (Depression, Anxiety, and Stress Scale) and PHQ-9 (Patient Health Questionnaire-9) questionnaires were employed to measure mental health. The DASS assesses symptoms of depression, anxiety, and stress, while the PHQ-9 specifically evaluates depression severity. Academic performance was evaluated using a 12-point scale, which incorporated various criteria such as exam scores, coursework performance, and participation in extracurricular activities. The research was conducted across five faculties of the university from 2022 to 2023. In the study, fifth-year students demonstrated a higher level of mental health compared to first-year students, with an average DASS score of 27.1 and 24.2, respectively. Interestingly, despite this, first-year students achieved higher academic performance indicators, with an average score of 8.2 compared to 9.8 in fifth-year students. Correlation analysis revealed significant associations between stress, depression, and anxiety levels with academic performance (stress: r = -0.25, p < 0.001; depression: r = -0.20, p = 0.003; anxiety: r = -0.18, p = 0.008). These findings highlight the critical importance of addressing students' mental well-being, particularly in later academic years. Recommendations include implementing support programs and developing online resources for students.

2.
Atherosclerosis ; : 117574, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38797614

RESUMEN

BACKGROUND AND AIMS: Albuminuria is an established risk factor for adverse cardiovascular outcomes. However, few studies have characterized longitudinal albuminuria patterns based on long-term measurement of urine albumin-to-creatinine ratio (UACR) levels. We aimed to evaluate the association between longitudinal albuminuria patterns in midlife adults and subsequent CAC progression. METHODS: We included 1919 participants with CAC assessment by computed tomography from CARDIA (Coronary Artery Risk Development in Young Adults) study. CAC progression was determined for each individual as the difference of logarithmic CAC scores at follow-up and baseline. Albuminuria patterns across a 10-year span were estimated by longitudinal UACR levels. Multivariable general linear models were used to evaluate the association of long-term albuminuria patterns with CAC progression. RESULTS: Of the 1919 included participants, 583 (30.4 %) participants experienced CAC progression, and the mean (SD) age was 50.4 (3.5) years at year 25. A total of four dynamic albuminuria patterns were identified. After multivariable adjustment, there were significant differences in CAC progression by albuminuria patterns as demonstrated as percent change in CAC with 36.0 % (SE, 1.5) progression for mid- and late-life normoalbuminuria group, 46.0 % (SE, 7.6) for midlife normoalbuminuria and late-life high albuminuria group, 52.4 % (SE, 7.1) for midlife high albuminuria and late-life normoalbuminuria group, and 54.5 % (SE, 8.7) for mid- and late-life high albuminuria group (p = 0.019). Similar findings were also observed in CAC volume score changes. CONCLUSIONS: Longitudinal albuminuria patterns across a 10-year span were associated with worse CAC progression independent of baseline CAC level and albuminuria changes, suggesting that it may provide early identification of high-risk individuals with dynamic rises in albuminuria who may benefit from aggressive risk factor modification.

3.
J Control Release ; 366: 838-848, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38145663

RESUMEN

Doxorubicin, an anthracycline chemotherapeutic agent, elicits a deleterious cardiotoxicity known as doxorubicin-induced cardiomyopathy (DIC) that circumscribes its chemotherapy utility for malignancies. Recent empirical evidence implicates ferroptosis, an iron-dependent form of regulated cell death, as playing a pivotal role in the pathogenesis of DIC. We postulated that anti-ferroptosis agents may constitute a novel therapeutic strategy for mitigating DIC. To test this hypothesis, we engineered baicalin-peptide supramolecular self-assembled nanofibers designed to selectively target the angiotensin II type I receptor (AT1R), which is upregulated in doxorubicin-damaged cardiomyocytes. This enabled targeted delivery of baicalin, a natural antioxidant compound, to inhibit ferroptosis in the afflicted myocardium. In vitro, the nanofibers ameliorated cardiomyocyte death by attenuating peroxide accumulation and suppressing ferroptosis. In a murine model of DIC, AT1R-targeted baicalin delivery resulted in efficacious cardiac accumulation and superior therapeutic effects compared to systemic administration. This investigation delineates a promising framework for developing targeted therapies that alleviate doxorubicin-induced cardiotoxicity by inhibiting the ferroptosis pathway in cardiomyocytes.


Asunto(s)
Ferroptosis , Flavonoides , Nanofibras , Animales , Ratones , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/prevención & control , Doxorrubicina , Miocitos Cardíacos , Péptidos/uso terapéutico
4.
ACS Nano ; 17(24): 24773-24789, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38055864

RESUMEN

As the prevalence of vascular calcification (VC), a strong contributor to cardiovascular morbidity and mortality, continues to increase, the need for pharmacologic therapies becomes urgent. Sodium thiosulfate (STS) is a clinically approved drug for therapy against VC; however, its efficacy is hampered by poor bioavailability and severe adverse effects. Plant-derived extracellular vesicles have provided options for VC treatment since they can be used as biomimetic drug carriers with higher biosafety and targeting abilities than artificial carriers. Inspired by natural grapefruit-derived extracellular vesicles (EVs), we fabricated a biomimetic nanocarrier comprising EVs loaded with STS and further modified with hydroxyapatite crystal binding peptide (ESTP) for VC-targeted delivery of STS. In vitro, the ESTP nanodrug exhibited excellent cellular uptake capacity by calcified vascular smooth muscle cells (VSMCs) and subsequently inhibited VSMCs calcification. In the VC mice model, the ESTP nanodrug showed preferentially the highest accumulation in the calcified arteries compared to other treatment groups. Mechanistically, the ESTP nanodrug significantly prevented VC via driving M2 macrophage polarization, reducing inflammation, and suppressing bone-vascular axis as demonstrated by inhibiting osteogenic phenotype trans-differentiation of VSMCs while enhancing bone quality. In addition, the ESTP nanodrug did not induce hemolysis or cause any damage to other organs. These results suggest that the ESTP nanodrug can prove to be a promising agent against VC without the concern of systemic toxicity.


Asunto(s)
Citrus paradisi , Vesículas Extracelulares , Calcificación Vascular , Animales , Ratones , Biomimética , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/metabolismo , Calcificación Vascular/prevención & control , Vesículas Extracelulares/metabolismo
5.
J Inflamm (Lond) ; 20(1): 44, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38115057

RESUMEN

OBJECTIVE: Lonicera japonica Thunb (LJT) is a commonly used herbal soup to treat inflammation-related diseases. However, the effect of LJT on ALI is unknown. The present study was aimed at investigating the protective effects of LJT extract (LTE) and its active ingredient luteolin (Lut) on lipopolysaccharide (LPS)-stimulated ALI and investigate its potential mechanism. MATERIALS AND METHODS: The effects of LTE and Lut were explored in an ALI mouse model induced by intraperitoneal injection of lipopolysaccharide (LPS). Besides, the LPS-induced inflammation model in BEAS-2B cells was used to clarify the underlying mechanisms. The ALI pathological changes in lung tissues were tested through Haematoxylin and eosin (HE) staining. The apoptosis of cells in lung tissue and the cell model in vitro was evaluated by TUNEL assays, respectively. Meanwhile, the viability of cells in vitro was evaluated by Cell Counting Kit-8 (CCK-8) assay. The levels/concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß and IL-10 in BALF were detected by enzyme-linked immunosorbent assay (ELISA). Besides, through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, the expression of the above-mentioned inflammatory factors and key factors in the NF-κB signaling pathway was examined. The distribution of inflammatory factors in tissue was observed through immunohistochemistry (IHC) assays . RESULTS: In relative to LPS-stimulated group, the in vivo study showed that LTE and different concentrations of Lut dramatically alleviated LPS-evoked lung pathological injury and lung edema based on the changes in total protein levels and lung wet/dry (W/D) ratio in the bronchoalveolar lavage fluid (BALF) from ALI mice. LTE and different concentrations of Lut also suppressed the inflammatory response, as reflected by the variations of neutrophil accumulation and the production of proinflammatory and anti-inflammatory cytokines in the lung tissues and BALF of ALI mice. The in vitro research also demonstrated that LTE and Lut visibly facilitated cell viability and restrained the apoptosis of BEAS-2B cells stimulated by LPS. Lut hindered LPS-inducible activation of NF-κB pathway in BEAS-2B cells. CONCLUSION: The present study proved that LTE might suppress LPS-induced acute injury and inflammation in mice and BEAS-2B cells through the Lut-caused suppression of NF-κB signal path (Figure 1).

6.
Materials (Basel) ; 16(17)2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37687571

RESUMEN

The effects of phosphoric acid (H3PO4) in pressurized aqueous solution on the dehydration of CaSO4·2H2O to form α-hemihydrate gypsum (α-HH) phase and the regulation of crystal shape were studied in this paper in order to provide guidance for the low-cost and high-value utilization of phosphogypsum. The results showed that H3PO4 can significantly accelerate the formation rate of the α-HH phase and that it did not participate in the formation of the α-HH phase in the form of eutectic phosphorus during crystalline phase transformation. In terms of crystal shape regulation, H3PO4 can impact the effect of a citric acid crystal regulator on α-HH crystal shape regulation. The more H3PO4 added, the greater the aspect ratio of α-HH. Accordingly, the water consumption and 2 h dry compressive strength of α-HH products were gradually increased and decreased with an increase in H3PO4 content, respectively. Despite this, the compressive strength of α-HH can still meet the requirements of the α20 grade in JC/T 2038-2010 "α High Strength Gypsum" in China when the H3PO4 content was limited to less than 0.4%.

7.
Environ Sci Pollut Res Int ; 30(11): 29598-29609, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36414898

RESUMEN

Despite the growing literature on the inequality-emissions nexus, this area of empirical interest is still inconclusive, particularly in the era of globalization. Hence, this empirical work investigates the effect of income inequality on carbon dioxide (CO2) emissions controlling the model for globalization. Considering the unique characteristics of various proxies of inequality, different proxies have been employed to develop an in-depth understanding of the inequality-emission nexus. The Driscoll-Kraay and generalized least square regression approaches are used for 38 sub-Saharan African countries from 1990 to 2016. Empirical results infer that higher income inequality promotes carbon reduction in the sample countries of the study. Further, findings suggest that globalization is beneficial for the environment by contributing to carbon emission mitigation. Several additional variables are used to validate the findings. The study offers some important policy implications in the end.


Asunto(s)
Desarrollo Económico , Renta , Internacionalidad , Ambiente , Dióxido de Carbono/análisis , África del Sur del Sahara
8.
Chin J Integr Med ; 29(4): 325-332, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35997860

RESUMEN

OBJECTIVE: To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro. METHODS: In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA). RESULTS: GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil. CONCLUSIONS: GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.


Asunto(s)
Antidiarreicos , Glycyrrhiza uralensis , Ratones , Conejos , Animales , Antidiarreicos/efectos adversos , Yeyuno , Aceite de Ricino/efectos adversos , Cloruro de Calcio/efectos adversos , Diarrea/tratamiento farmacológico , Extractos Vegetales/efectos adversos , Verapamilo/efectos adversos , Contracción Muscular
9.
Pak J Pharm Sci ; 35(2): 571-578, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35642414

RESUMEN

Scutellaria barbata (S. barbata), a traditional herbal medicine used in southern China, possesses anti-inflammatory, antitumor, spasmolytic and expectorant effects. However, there are not many recent studies on its gastrointestinal effects. This study aimed to evaluate the antidiarrheal effect of the ethanol extract of S. barbata (SBE) and its effect on the isolated jejunum smooth muscle. METHODS: The antidiarrheal effect of SBE (doses: 125, 250 and 500 mg/kg) on castor oil-induced diarrhea was investigated in vivo. The effect of SBE (0.01-10 mg/mL) on spontaneous or acetylcholine chloride (ACh, 10µM)/KCl (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was examined in vitro. The possible spasmolytic mechanism of SBE (1 and 3mg/mL) was analyzed by accumulating CaCl2 in a Ca2+-free high-K+ (60mM) solution. RESULTS: SBE (125, 250 and 500mg/kg) could delay the initial semi-solid onset time of mice and also reduce the diarrhea index in vivo. Furthermore, SBE (0.01-10mg/mL) could alleviate the spontaneous or ACh/KCl-induced contraction in vitro. SBE (1 and 3mg/mL) also inhibited the contraction induced by CaCl2, and the concentration-response curves of CaCl2 moved downward and to the right, similar to those of verapamil (0.01 and 0.1µM). CONCLUSIONS: SBE exerts antidiarrheal and spasmolytic effects, which provides a pharmacological basis for its use in functional gastrointestinal disorders.


Asunto(s)
Antineoplásicos , Scutellaria , Animales , Antidiarreicos/uso terapéutico , Antineoplásicos/farmacología , Cloruro de Calcio/efectos adversos , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Etanol/farmacología , Yeyuno , Músculo Liso , Parasimpatolíticos/farmacología , Extractos Vegetales/uso terapéutico , Conejos
10.
Pak J Pharm Sci ; 35(2): 587-594, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35642416

RESUMEN

Lophatheri Herba is a traditional Chinese medicine, which is commonly used in the treatment of fever, stomatitis, urodynia. The aim of the study is to evaluate the antidiarrheal activity of the ethanol extract of Lophatheri Herba (Gramineae, ELH) and observe its effect on isolated jejunum smooth muscle in rabbits, so that we can provide a possible pharmacological basis for its clinical use. Methods: In vivo, the antidiarrheal activity of ELH (250, 500 and 1000 mg/kg; orally) in castor oil-induced Kun Ming mice was evaluated. In vitro, the effect of ELH (0.01-10 mg/mL) on the spontaneous and ACh (10µM)/K+ (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was studied. The possible mechanism of spasmolytic effect of ELH (1, 3mg/mL) was explored by pretreatment of intestinal tract with CaCl2. Results: ELH (500 and 1000mg/kg) exhibited antidiarrheal effect and it (0.01-10 mg/mL) inhibited the spontaneous and ACh/K+-induced contraction with an EC50 value of 1.27 (0.89-1.34), 0.76 (0.54-1.02) and 0.34 (0.27-0.53), it also shifted the concentration-response curves of CaCl2 to right with decreased in max, similar to verapamil. ELH has significant antidiarrheal and spasmolytic effect, this provides the pharmacological basis for use in gastrointestinal disorders.


Asunto(s)
Antidiarreicos , Parasimpatolíticos , Animales , Antidiarreicos/farmacología , Cloruro de Calcio/farmacología , Etanol/farmacología , Yeyuno , Ratones , Músculo Liso , Parasimpatolíticos/farmacología , Extractos Vegetales/farmacología , Conejos
11.
Biol Pharm Bull ; 45(7): 863-871, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35491088

RESUMEN

Saikosaponin A (SSA)-a natural compound extracted from Radix bupleuri-possesses antitumor properties in several types of carcinomas. However, the role of SSA on bladder cancer and the mechanisms remain unclear. In this study, we have described the effect of SSA on human bladder cancer cell lines T24 and 5637 in the context of the regulation of mitochondrial pathways of apoptosis. In vitro, the Cell Counting Kit-8 (CCK-8) assay and cell wound healing assays were used to determine the proliferative effect of SSA treatment. Flow cytometry and Western blotting were performed to evaluate the apoptosis and related mechanisms. To further confirm that apoptosis is mediated through Caspase activation, Hoechst 33258 fluorescence staining assay was done after cells were treated with SSA and caspase inhibitor-Z-VAD-FMK. In vivo, an orthotopic xenograft mice model was adopted to evaluate the effect of SSA. The tumors were analyzed by hematoxylin-eosin (H&E) staining, immunohistochemical analysis, and Western blotting. In vitro, the results with CCK-8 assay showed obvious SSA-induced suppression in cell growth in a dose- and time-dependent manner. Flow cytometry analysis, Hoechst 33258 fluorescence staining assay and the assessment of the changes in the B-cell lymphoma 2 (Bcl-2) family protein expression level revealed that SSA could significantly induce cell apoptosis, which was associated with apoptosis via the mitochondrial pathways. In vivo, the results revealed a reduction in cell proliferation. In conclusion, our data suggest that SSA inhibits the growth of bladder cancer cells by activating the mitochondrial apoptosis pathway and inducing cell apoptosis.


Asunto(s)
Carcinoma , Neoplasias de la Vejiga Urinaria , Animales , Apoptosis , Bisbenzimidazol/farmacología , Caspasas , Línea Celular Tumoral , Proliferación Celular , Humanos , Ratones , Ácido Oleanólico/análogos & derivados , Saponinas , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
12.
Angew Chem Int Ed Engl ; 61(30): e202203398, 2022 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-35594364

RESUMEN

A novel distal radical rearrangement of alkoxyphosphine is developed for the first time and applied to the regioselective radical fluoroalkylphosphorylation of unactivated olefins. By employing a one-pot two-step reaction of (bis)homoallylic alcohols, organophosphine chlorides, and fluoroalkyl iodides under CFL (compact fluorescence light) irradiation, a series of fluoroalkylphosphorylated alkyl iodides and alcohols are easily synthesized by regiospecific installing a phosphonyl onto the inner carbon of terminal olefins and further iodination/hydroxylation. Mechanism studies reveal that the migration undergoes a distinctive radical cyclization/ß-scission on the lone electron pair of phosphorus, resulting in C-P bond formation and C-O bond cleavage.

13.
Org Lett ; 24(2): 542-547, 2022 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-34989585

RESUMEN

A radical [1,4]-oxygen-atom transfer has been realized by the reaction of linear alkyne-tethered ketoximes and ethynylbenziodoxolones (EBX) under sequential catalytic conditions. Mechanism studies indicate that the O atom transfer experiences a cascade O atom radical cyclization/alkynylation/N-O bond photocleavage and subsequent N,O-diradical rearrangement. By the diversification of catalytic sequences, a series of structurally important 3H-pyrrol-3-ones and chlorinated furo[3,2-b]pyrroles are divergently synthesized along with an O atom shift under the catalysis of Cu/Ir photosensitization and Cu/Ir photosensitization/AlCl3, respectively.

14.
Chest ; 161(4): 1036-1045, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34740593

RESUMEN

BACKGROUND: Respiratory and cardiovascular diseases (CVDs) frequently coexist; however, there is limited evidence on the relationship between chronic respiratory symptoms in young adulthood and late-onset CVD. RESEARCH QUESTION: Are chronic respiratory symptoms in young adulthood associated with CVD and all-cause mortality in later life? STUDY DESIGN AND METHODS: A total of 4,621 participants from the Coronary Artery Risk Development in Young Adults Study (CARDIA) cohort study aged 18 to 30 years were included. Chronic respiratory symptoms were identified through respiratory symptom questionnaires in two consecutive examinations. Incident CVD and all-cause mortality were adjudicated over 30-year follow-up. Multivariable Cox proportional hazards models were used to explore the association of chronic respiratory symptoms with incident CVD and all-cause mortality. RESULTS: During a median follow-up of 30.9 years, 284 CVD events (6.15%) and 378 deaths (8.18%) occurred. Following multivariable adjustment for demographic characteristics, cardiovascular risk factors, smoking, and lung function, the hazard ratios (95% CIs) for CVD events were 1.51 (1.18-1.93) for any respiratory symptom, 1.57 (1.18-2.09) for cough or phlegm, 1.31 (1.01-1.68) for wheeze, 1.73 (1.25-2.41) for shortness of breath, and 1.32 (1.01-1.71) for chest illnesses. Similar findings were also observed in all-cause mortality. Comparing zero vs three to four respiratory symptoms, the hazard ratios (95% CIs) were 1.97 (1.34-2.91) for CVD and 1.75 (1.23-2.47) for all-cause mortality. Similar results were observed in various sensitivity analyses. INTERPRETATION: Chronic respiratory symptoms in young adulthood are associated with an increased risk of CVD and all-cause mortality in midlife independent of established cardiovascular risk factors, smoking, and lung function. Identifying chronic respiratory symptoms in young adulthood may help provide prognostic information regarding future cardiovascular health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT00005130; URL: https://www. CLINICALTRIALS: gov.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedades Respiratorias , Adolescente , Adulto , Enfermedades Cardiovasculares/epidemiología , Causas de Muerte , Enfermedad Crónica , Estudios de Cohortes , Vasos Coronarios , Humanos , Incidencia , Modelos de Riesgos Proporcionales , Enfermedades Respiratorias/epidemiología , Factores de Riesgo , Adulto Joven
15.
Peptides ; 147: 170705, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34822913

RESUMEN

Corticotropin-releasing factor (CRF) is a 41-amino acid polypeptide that coordinates the endocrine system, autonomic nervous system, immune system, and physiological behavior. CRF is a signaling regulator in the neuro-endocrine-immune (NEI) network that mediates visceral hypersensitivity. Rodent models to simulate changes in intestinal motility similar to those reported in the irritable bowel syndrome (IBS), demonstrate that the CRF receptor 1 (CRF-R1) mediates intestinal hypersensitivity under many conditions. However, the translation of preclinical studies into clinical trials has not been successful possibly due to the lack of sufficient understanding of the multiple variants of CRF-R1 and CRF-R1 antagonists. Investigating the sites of action of central and peripheral CRF is critical for accelerating the translation from preclinical to clinical studies.


Asunto(s)
Hormona Liberadora de Corticotropina/metabolismo , Síndrome del Colon Irritable/tratamiento farmacológico , Síndrome del Colon Irritable/etiología , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Animales , Encéfalo/metabolismo , Motilidad Gastrointestinal/fisiología , Humanos , Síndrome del Colon Irritable/psicología , Receptores de Hormona Liberadora de Corticotropina/metabolismo
17.
Front Sociol ; 6: 738134, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34692818

RESUMEN

The institutional environment not only has a great impact on economic development but also has a certain impact on labor agglomeration. This paper explains the phenomenon of labor agglomeration from the perspective of the labor market institutional environment. Taking the labor market institutional environment including social contract environment and labor contract environment as the premise, it is considered that a good labor institutional market can promote labor agglomeration and technological progress can stimulate the agglomeration of highly-skilled talents through theoretical analysis. Based on the provincial panel data from 2001 to 2017, the empirical analysis is conducted to verify the relevant factors through the dynamic spatial Durbin model. The paper finally puts forward some policy suggestions to maintain a good institutional environment of the labor market, including that the local government should continue to improve the labor dispute settlement system, strengthen the protection of labor rights and interests, and enhance the institutional environment of the regional labor market.

18.
Angew Chem Int Ed Engl ; 60(50): 26308-26313, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-34437754

RESUMEN

A novel radical 1,4/5-amino shift from the oxygen center of alkene-tethered diphenyl ketoxime ethers to the carbon center to achieve high value-added fluoroalkyl-containing primary ß(γ)-amino-ketones is reported. Mechanism studies reveal that the migration is triggered by the alkene addition of fluoroalkyl radical derived from the electron donor-acceptor (EDA) complex of Togni's reagent II or fluoroalkyl iodides and quinuclidine, and involves a unique 5(6)-exo-trig cyclization of the carbon-centered radical onto the N-atom of ketoxime ethers followed by a cascade sequence of N-O bond cleavage and dehydrogenation. Notably, besides Togni's reagent II and fluoroalkyl iodides, this protocol is also compatible with other radical precursors to provide various functionalized primary aminoketones.

19.
Folia Neuropathol ; 59(2): 161-173, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34284544

RESUMEN

In this study, we investigated the neuroprotective effects of lycopene (Lyc) on vascular dementia (VaD) gerbils and its related mechanisms of anti-inflammatory, anti-apoptotic and anti-oxidant activity. Gerbils were treated with bilateral common carotid arteries. Animals were divided into 1) Sham, 2) VaD model, and 3) VaD model + Lyc (20 mg/kg) groups. Each group (3) was administered intergalactic Lyc twice a day for 28 days. Morris water mazes were used to evaluate learning and memory ability. Nissl, NeuN, and GFAP staining were used to observe histomorphological changes of neural and glial cells in the hippocampus CA1 region. Western blotting was used to detect hippocampus caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2 related × protein (Bax), and interleukin (IL)-1, IL-6 and tumour necrosis factor a (TNF-a) expression amongst other inflammatory factors. Secreted IL-1, IL-6 and TNF-a levels were assessed by ELISA in addition to superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione (GSH) and malondialdehyde (MDA). We found that Lyc increased the learning and memory ability of gerbils by reducing the latency time in the Morris water maze, and increasing spatial memory. Lyc also reduced pathological changes in the hippocampus caused by VaD, reduced apoptosis, and decreased VaD mediated Bcl-2/Bax expression. The levels of inflammatory factors and oxidative stress were also reduced by Lyc in the VaD models. We therefore conclude that Lyc can improve the learning and memory ability of VaD gerbils, the mechanism of which may be related to reduced oxidative stress and apoptosis in VaD hippocampus neurons.


Asunto(s)
Demencia Vascular , Animales , Demencia Vascular/tratamiento farmacológico , Suplementos Dietéticos , Gerbillinae , Hipocampo , Licopeno , Aprendizaje por Laberinto , Estrés Oxidativo
20.
ACS Appl Mater Interfaces ; 13(19): 22131-22141, 2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-33957750

RESUMEN

The reconstruction of blood perfusion is a crucial therapeutic method to save and protect cardiac function after acute myocardial infarction (AMI). The activation of the hepatocyte growth factor precursor (pro-HGF) has a significant effect on promoting angiogenesis and antiapoptosis. The oxygen/glucose deprivation (OGD) caused by AMI could induce vascular adventitia fibroblasts to differentiate into myofibroblasts and secrete the pro-HGF. Meanwhile, the specific Met receptor of the hepatocyte growth factor (HGF) is upregulated in endothelial cells during AMI. However, the poor prognosis of AMI suggests that the pro-HGF is not effectively activated. Improving the activation efficiency of the pro-HGF may play a positive role in the treatment of AMI. Herein, we designed supramolecular nanofibers self-assembled by compound 1 (Comp.1, Nap-FFEG-IVGGYPWWMDV), which can strongly activate the pro-HGF and initiate HGF-Met signaling. Studies have proven that Comp.1 possesses a better ability to activate the pro-HGF to perform antiapoptosis and pro-angiogenesis. In vivo results have confirmed that the retention time of Comp.1 and its accumulation in the infarct area of the heart are promoted. Moreover, Comp.1 plays an effective role in promoting angiogenesis in the marginal area of AMI, reducing myocardial fibrosis, and protecting cardiac function. Herein, we will optimize the structure of bioactive peptides through supramolecular self-assembly and amplify their therapeutic effect by improving their efficiency, providing a new strategy for the therapy of AMI.


Asunto(s)
Factor de Crecimiento de Hepatocito/metabolismo , Infarto del Miocardio/terapia , Nanofibras , Neovascularización Patológica , Precursores de Proteínas/metabolismo , Secuencia de Aminoácidos , Factor de Crecimiento de Hepatocito/química , Células Endoteliales de la Vena Umbilical Humana , Humanos , Nanofibras/química , Precursores de Proteínas/química , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo
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