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Liquid porosimetry experiments reveal a peculiar trend of the intrusion pressure of water in hydrophobic Cu2(3,3',5,5'-tetraethyl-4,4'-bipyrazolate) MOF. At lower temperature (T) range, the intrusion pressure (Pi) increases with T. For higher T values, Piâ first reaches a maximum and then decreases. This is at odds with the Young-Laplace law, which for systems showing a continuous decrease of contact angle with T predicts a corresponding reduction of the intrusion pressure. Though the Young-Laplace law is not expected to provide quantitative predictions at the subnanoscale of Cu2(tebpz) pores, the physical intuition suggests that to a reduction of their hydrophobicity corresponds a reduction of the Pi. Molecular dynamics simulations and sychrothron experiments allowed to clarify the mechanism of the peculiar trend of Pi with T. At increasing temperatures the vapor density within the MOF' pores grows significantly, bringing the corresponding partial pressure to ≈5 MPa. This pressure, which is consistent with the shift of Pi observed in liquid porosimetry, represents a threshold to be overcame before intrusion takes place. Beyond some value of temperature, the phenomenon of reduction of hydrophobicity (and water surface tension) dominated over the opposite effect of increase of vapor pressure and Pi inverts its trend with T.
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Fluids under extreme confinement show characteristics significantly different from those of their bulk counterpart. This work focuses on water confined within the complex cavities of highly hydrophobic metal-organic frameworks (MOFs) at high pressures. A combination of high-pressure intrusion-extrusion experiments with molecular dynamic simulations and synchrotron data reveals that supercritical transition for MOF-confined water takes place at a much lower temperature than in bulk water, â¼250 K below the reference values. This large shifting of the critical temperature (Tc) is attributed to the very large density of confined water vapor in the peculiar geometry and chemistry of the cavities of Cu2tebpz (tebpz = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate) hydrophobic MOF. This is the first time the shift of Tc is investigated for water confined within highly hydrophobic nanoporous materials, which explains why such a large reduction of the critical temperature was never reported before, neither experimentally nor computationally.
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H2A.Z, one of the most well-known variants of histone H2A, has been extensively investigated on its dual roles in gene transcription in recent years. In this review, we focus on the intricate involvement of H2A.Z in transcriptional regulation, including the assembly of distinct H2A.Z subtypes, post-translational modifications and genomic distributions. Emphasis is placed on the biological and pathophysiological implications, particularly in tumorigenesis and nervous system development. We summarize the dynamic regulatory mechanisms governing H2A.Z deposition or eviction on chromatin to provide insights for understanding the diversity of histone variants and promoting the search of new targets in concerned disease diagnosis and treatment.
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Histonas , Nucleosomas , Histonas/metabolismo , Cromatina , Regulación de la Expresión Génica , GenomaRESUMEN
This study induced biological stress in Sorbus pohuashanensis suspension cell(SPSC) with yeast extract(YE) as a bio-tic elicitor and isolated and identified secondary metabolites of triterpenoids produced under stress conditions. Twenty-six triterpenoids, including fifteen ursane-type triterpenoids(1-15), two 18,19-seco-ursane-type triterpenoids(16-17), four lupine-type triterpenoids(18-21), two cycloartane-type triterpenoids(22-23), and three squalene-type triterpenoids(24-26), were isolated and purified from the methanol extract of SPSC by chromatography on silica gel, MCI, Sephadex LH-20, and MPLC. Their structures were elucidated by spectroscopic analyses. All triterpenoids were isolated from SPSC for the first time and 22-O-acetyltripterygic acid A(1) was identified as a new compound. Selected compounds were evaluated for antifungal, antitumor, and anti-inflammatory activities, and compound 1 showed an inhibitory effect on NO production in LPS-induced RAW264.7 cells.
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Triterpenos Pentacíclicos , Sorbus , Triterpenos , Animales , Ratones , Sorbus/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Células RAW 264.7 , Estructura MolecularRESUMEN
BACKGROUND: Gastrointestinal motility disorders tend to develop after pancreaticoduodenectomy (PD). The objectives of this study were: (1) to investigate the impact of needleless transcutaneous neuromodulation (TN) on the postoperative recuperation following pancreaticoduodenectomy (PD), and (2) to explore the underlying mechanisms by which TN facilitates the recovery of gastrointestinal function after PD. METHODS: A total of 41 patients scheduled for PD were randomized into two groups: the TN group (n = 21) and the Sham-TN group (n = 20). TN was performed at acupoints ST-36 and PC-6 twice daily for 1 h from the postoperative day 1 (POD1) to day 7. Sham-TN was performed at non-acupoints. Subsequent assessments incorporated both heart rate variation and dynamic electrogastrography to quantify alterations in vagal activity (HF) and gastric pacing activity. RESULTS: 1)TN significantly decreased the duration of the first passage of flatus (p < 0.001) and defecation (p < 0.01) as well as the time required to resume diet (p < 0.001) when compared to sham-TN;2)Compared with sham-TN, TN increased the proportion of regular gastric pacing activity (p < 0.01);3) From POD1 to POD7, there was a discernible augmentation in HF induced by TN stimulation(p < 0.01);4) TN significantly decreased serum IL-6 levels from POD1 to POD7 (p < 0.001);5) TN was an independent predictor of shortened hospital stay(ß = - 0.349, p = 0.035). CONCLUSION: Needleless TN accelerates the recovery of gastrointestinal function and reduces the risk of delayed gastric emptying in patients after PD by enhancing vagal activity and controlling the inflammatory response.
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Pancreaticoduodenectomía , Estómago , Humanos , Pancreaticoduodenectomía/efectos adversos , Tiempo de Internación , Vaciamiento Gástrico , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiologíaRESUMEN
PURPOSE: Older individuals are priority coronavirus disease 2019 (COVID-19) vaccine recipients. Our aim was to investigate the prevalence of and factors influencing vaccine hesitancy in older individuals living in nursing homes and communities. METHODS: A self-administered COVID-19 vaccine hesitancy survey was conducted from September 2021 to December 2021 among people aged ≥ 60 years in eight nursing homes (382 participants) and the community (112 participants) in Taizhou, China. The response rate was 72.1% (382/530) for older adults in nursing homes and 68.7% (112/163) for older adults in the community. RESULTS: We found that 58.1% of the older individuals in nursing homes and 36.6% of those in the community were hesitant to receive the COVID-19 vaccine and that there was a statistically significant difference (P < 0.001). Multiple logistic regression results indicated that the main factors influencing hesitation among the older individuals in nursing homes were being male (Odds Ratio (OR) = 1.67, 95% Confidence Interval (CI): 1.01-2.76); their cognitive level, including having a high perceived risk of COVID-19 infection (OR = 3.06, 95% CI: 1.73-5.43) or the perception of low vaccine safety (OR = 3.08, 95% CI: 1.545- 6.145); anxiety (OR = 3.43, 95% CI: 1.96-5.99); and no previous influenza vaccination (OR = 1.82, 95% CI: 1.13-2.93); whereas those for older individuals in the community were comorbid chronic diseases (OR = 3.13, 95% CI: 1.11- 8.78) and community workers not recommending the vaccine (OR = 8.223, 95% CI: 1.77-38.27). CONCLUSION: The proportion of older individuals in nursing homes who were hesitant to receive the COVID-19 vaccine was significantly higher than for older individuals in the community. Targeted measures should be implemented to reduce vaccine hesitancy and improve vaccination rates in response to the special environment of nursing homes and the characteristics of this population.
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COVID-19 , Humanos , Masculino , Anciano , Femenino , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Vacunación , China/epidemiología , Casas de SaludRESUMEN
To investigate the response mechanisms of soil bacterial and fungal communities to the changes of preci-pitation in a desert steppe of Ningxia, we conducted a three-year precipitation control experiment following completely randomized design. There were five treatments, natural precipitation (T0), 50% less in precipitation (T1), 25% less in precipitation (T2), 25% more in precipitation (T3) and 50% more in precipitation (T4). By using Illumina high-throughput sequencing and bioinformatics analysis, we investigated the effects of increased and decreased precipitation on soil bacterial and fungal communities, and examined the correlations between soil physicochemical properties, plant communities and soil bacterial and fungal communities. The result showed that the richness of soil bacteria and fungi was highest in the T4 treatment. In addition, the relative abundance of Chloroflexi, the predominant phyla of soil bacteria was more sensitive to precipitation change. However, the relative abundance of only Ascomycota, a rare fungal taxon, responded to precipitation changes. Results of redundancy analysis showed that the first two axes accounted for 92.8% and 87.4% of the total variance for soil bacterial and fungal community composition, respectively. Precipitation and soil pH were the most important environmental factors driving changes in soil bacterial diversity and community composition. On the one hand, precipitation had a direct positive effect on bacterial diversity and community composition. On the other hand, precipitation changed pH by affecting soil moisture, which in turn had a significant indirect effect on bacterial diversity and community composition. Plant community biomass, plant species richness, and soil pH were the most influential environmental factors affecting fungal diversity and community composition. Precipitation had no direct effect on soil fungal community, but had a significant indirect effect by changing plant community richness and soil pH. The response mechanisms of bacterial and fungal communities in soil differed significantly under different precipitation regimes in the desert grasslands of Ningxia.
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Micobioma , Bacterias , Biomasa , Secuenciación de Nucleótidos de Alto Rendimiento , SueloRESUMEN
As an important bridge connecting aboveground communities and belowground biological processes, soil microorganisms play an important role in regulating belowground ecological processes. The altitudinal changes and driving factors of soil microbial community in mountain ecosystem in arid region are still unclear. We measured soil physicochemical properties at seven altitudes in the range of 1300-2800 m in Helan Mountains, and investigated the understory community composition, soil physicochemical properties, and soil microbial community. The driving factor for soil microbial community was explored by variance partitioning analysis and redundancy analysis. The results showed that the total amount of soil microorganisms and bacterial biomass first increased and then decreased with the increases of altitude, fungi, actinomyces, arbuscular mycorrhizal fungi, Gram-positive bacteria, and Gram-negative bacteria groups showed a gradual increase. The variation of fungal-to-bacterial ratio (F/B) along the altitude showed that the cumulative ability of soil bacteria was stronger than that of fungi at low altitudes, while the pattern is opposite at high altitudes. The ratio of Gram-positive bacteria to Gram-negative bacteria (GP/GN) showed an overall decreasing trend with the increases of altitude, indicating that soil bacteria and organic carbon availability changed from "oligotrophic" to "eutrophication" and from "low" to "high" transition as the altitude increased. Vegetation properties, soil physical and chemical properties jointly accounted for 95.7% of the variation in soil microbial community. Soil organic carbon (SOC), soil water content (SWC), and total nitrogen (TN) were significantly correlated with soil microbial community composition. Our results revealed the distribution pattern and driving factors of soil microbial communities at different elevations on the eastern slope of Helan Mountain, which would provide theoretical basis and data support for further understanding the interaction between plant-soil-microorganisms in arid areas.
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Carbono , Microbiota , Suelo , Altitud , ChinaRESUMEN
Intestinal fibrosis is a common complication of inflammatory bowel disease. There is still a lack of effective drugs for the prevention or treatment of intestinal fibrosis. Heat shock protein 47 (HSP47) plays a key role in the development of intestinal fibrosis. In this study we investigated the therapeutic potential and underlying mechanisms of fraxinellone, a degraded limonoid isolated from the root bark of Dictamnus dasycarpus, in the treatment of intestinal fibrosis. Intestinal fibrosis was induced in mice by dextran sodium sulfate (DSS) treatment. DDS-treated mice were administered fraxinellone (7.5, 15, 30 mg·kg-1·d-1, i.g.) for 45 days. We showed that fraxinellone administration dose-dependently alleviated DSS-induced intestinal impairments, and reduced the production of intestinal fibrosis biomarkers such as α-smooth muscle actin (SMA), collagen I, hydroxyproline, fibronectin and laminin, and cytokines such as TGF-ß, TNF-α and IL-ß. We then established in vitro intestinal fibrosis cell models in SW480 and HT-29 cells, and demonstrated that treatment with fraxinellone (3, 10, 30 µM) significantly relieved TGF-ß-induced fibrosis responses by inhibiting the TGF-ß/Smad2/3 signaling pathway. Molecular docking suggested that the fraxinellone might disrupt the interaction between HSP47 and collagen, which was confirmed by coimmunoprecipitation experiments. SPR analysis showed that fraxinellone had a high affinity for HSP47 with a Kd value of 3.542 × 10-5 M. This study provides a new example of HSP47-collagen intervention by a natural compound and has important implications for the clinical treatment of inflammation-induced issue fibrosis.
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Colágeno , Proteínas del Choque Térmico HSP47 , Ratones , Animales , Proteínas del Choque Térmico HSP47/metabolismo , Simulación del Acoplamiento Molecular , Colágeno/metabolismo , Fibrosis , Epitelio/metabolismo , Factor de Crecimiento Transformador betaRESUMEN
Tin disulfide (SnS2 ) is a promising candidate for electrosynthesis of CO2 -to-formate while the low activity and selectivity remain a great challenge. Herein, we report the potentiostatic and pulsed potential CO2 RR performance of SnS2 nanosheets (NSs) with tunable S-vacancy and exposure of Sn-atoms or S-atoms prepared controllably by calcination of SnS2 at different temperatures under the H2 /Ar atmosphere. The catalytic activity of S-vacancy SnS2 (Vs -SnS2 ) is improved 1.8â times, but it exhibits an exclusive hydrogen evolution with about 100 % FE under all potentials investigated in the static conditions. The theoretical calculations reveal that the adsorption of *H on the Vs -SnS2 surface is energetically more favorable than the carbonaceous intermediates, resulting in active site coverage that hinders the carbon intermediates from being adsorbed. Fortunately, the main product can be switched from hydrogen to formate by applying pulsed potential electrolysis benefiting from in situ formed partially oxidized SnS2-x with the oxide phase selective to formate and the S-vacancy to hydrogen. This work highlights not only the Vs -SnS2 NSs lead to exclusively H2 formation, but also provides insights into the systematic design of highly selective CO2 reduction catalysts reconstructed by pulsed potential electrolysis.
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OBJECTIVE: To explore the clinical application of lockedge suspension combined with three steel wires vertical fixation in comminuted fracture of inferior pole of patella. METHODS: From August 2016 to May 2019, 23 patients with comminuted fracture of the lower pole of the patella, including 14 males and 9 females, were treated with lockedge suspension combined with three steel wires vertical fixation. The age ranged from 34 to 68 (55.0±1.2) years. One year after operation, the pain and function were evaluated by pain visual analogue scale(VAS) and knee flexion and extension range of motion, and the clinical efficacy was evaluated by Lysholm knee score standard. RESULTS: All 23 patients were followed up for 12 to 14, with a mean of(13.0±0.5) months. One patient had skin irritation by the tail of the steel wire, and the rest had no postoperative complications such as incision infection, internal fixation loosening and fracture displacement. The fractures of 23 patients were healed, and the healing time was 10 to 14 weeks with a mean of(12.0±1.1) weeks. The VAS score decreased from 7.96±0.93 before operation to 0.83±0.65 one year after operation. The range of knee flexion and extension activities increased from(20.30±8.69) ° before operation to 1 year after operation(127.39±6.55) °. Lysholm knee score increased from 18.48±4.00 before operation to 96.09±4.91 one year after operation(P<0.05). CONCLUSION: The treatment of comminuted fracture of the lower pole of patella by lockedge suspension combined with three steel wires vertical fixation has reliable fixation and high fracture healing rate. It can meet the requirements of rapid rehabilitation and functional exercise, and the early clinical effect is satisfactory.
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Fracturas Óseas , Fracturas Conminutas , Adulto , Anciano , Hilos Ortopédicos , Femenino , Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Fracturas Conminutas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Rótula/cirugía , Acero , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore clinical effect of arthroscopic meniscus tear strapping suture by rotator cuff suture threader. METHODS: Forty patients with meniscus tear injury admitted from July 2015 to May 2019, including 27 males and 13 females, aged from 20 to 55 years old with an average of (36.0±1.4) years old. Menisci laceration was sutured with rotator cuff suture thread under arthroscopy. Postoperative complication was observed, Lysholm knee joint score before and after operation at 12 months were used to evaluate clinical effects, visual analogue scale (VAS) and range of knee flexion and extension were applied to evaluate recovery of pain and function. RESULTS: All patients were followed up from 12 to 15 months with an average of (12.6±0.7) months.No complication such as joint effusion, suture failure occurred. Two patients occurred mild pain after activity without clinical physical abnormality, and 1 patient manifested moderate pain with joint space tenderness, the other rest without abnormal. Lysholm knee joint score was increased from (49.55±1.21) preoperatively to (98.95±0.42) at 12 months after operation, VAS score decreased from (5.18±0.78)preoperatively to (1.03±0.77) at 12 months after operation, and range of knee joint flexion and extension activity increased from (50.63±9.20)°preoperatively to (130.38±4.99)°after operation, and there were statistical differences in Lysholm knee joint score, VAS and range of knee joint flexion and extension activity (P< 0.05). CONCLUSION: Arthroscopic strapping suture by rotator cuff suture threading device applies to most meniscus injuries, including medial meniscus posterior horn tears, lateral meniscus body tears and lateral meniscus posterior horn tears. This technique meets the need of full-internal meniscus suture without specialmeniscus suture, and has advantages of convenient operation, less complications and good postoperative function.
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Lesiones del Manguito de los Rotadores , Lesiones de Menisco Tibial , Adulto , Artroscopía , Femenino , Humanos , Masculino , Meniscos Tibiales/cirugía , Persona de Mediana Edad , Manguito de los Rotadores , Lesiones del Manguito de los Rotadores/cirugía , Técnicas de Sutura , Suturas/efectos adversos , Lesiones de Menisco Tibial/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
Depressive symptoms have been found to be highly prevalent among patients with coronary heart disease (CHD) and seriously affect the patients' quality of life. However, most psychotropic drugs have warnings about potential side effects. Accordingly, safer effective alternatives are urgently demanded. Angina pectoris of CHD is considered as "chest stuffiness and heartache syndrome" in traditional Chinese medicine, with the major syndrome type named Qi stagnation and blood stasis. Qi-regulating and blood circulation-promoting therapy has increasingly shown unique advantages in CHD patients. This study investigated the efficacy of Xuefu Zhuyu decoction, a representative prescription of Qi-regulating and blood circulation-promoting therapy, on angina pectoris patients with depressive symptoms. Depressive symptoms were stratified at baseline in 30 patients with stable angina pectoris who participated in both baseline and 12-week follow-up studies. After performing a stratified analysis, the angina pectoris-specific health status and traditional Chinese medicine "chest stuffiness and heartache syndrome" were evaluated by self-reports using the associated questionnaire scales, respectively. We measured serum concentrations of serotonin, brain-derived neurotrophic factor, and ATP, which are associated with the development of depression. We found that the Xuefu Zhuyu granule significantly improved the angina pectoris-specific health status in patients after 12 weeks of treatment; specifically, it had a better curative effect on patients with depressive symptoms. Xuefu Zhuyu granule also significantly improved the chest stuffiness and heartache syndrome in patients with depressive symptoms (efficacy index is 61.24%, P < 0.05 versus baseline). Interestingly, Xuefu Zhuyu granule has been found to be more susceptible to improving ATP levels in patients with depressive symptoms, indicating that the improvement in serum ATP levels might account for the better efficacy of Xuefu Zhuyu granule in patients with depressive symptoms. Our data provide prospective evidence that Xuefu Zhuyu granule improves angina pectoris-specific health status through regulating Qi and promoting blood circulation. This trial is registered with ChiCTR-IOR-15006989.
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Shape complementarity is a biological craft for precisely binding substrates at protein-protein interfaces. An analogy to such a function can be drawn conceptually for crystalline porous solids; yet the manifested entities are rare in reticular chemistry. The bottleneck-shaped pores carved out of a metal-organic framework, Zn(MIBA)2 (aka. MAF-stu-13), can perfectly accommodate benzene molecules. Remarkably, its framework adapts to the optimal guest binding-the enhanced host-guest interactions in the neck in turn minimize the guest-guest repulsion in the pore to the extent it turns into attraction-as demonstrated by the combined X-ray structural and DFT computational studies. This adaptive material can be used for liquid-phase production of ultrahigh-purity (≥99 %) cyclohexane, achieving a balance between uptake capacity and separation selectivity and surpassing the performances of other porous and nonporous crystals reported recently (e.g. product purity 99.4 % vs. 97.5 % to date).
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Ciclohexanos/aislamiento & purificación , Imidazoles/química , Estructuras Metalorgánicas/química , Ciclohexanos/química , Modelos Moleculares , Tamaño de la PartículaRESUMEN
Over the past decades, organometallic complexes with precious elements, such as ruthenium and iridium, are widely used as visible-light photoredox catalysts. Recently, more and more complexes based on earth-abundant and inexpensive elements have been used as sensitizers in photochemistry. Although the photoexcited state lifetimes of iron complexes are typically shorter than those of traditional photosensitizers, the utilization of iron catalysts in photochemistry has sprung up owing to their abundance, low price, nontoxicity, and novel properties, including exhibiting ligand to metal charge transfer states. This concept focuses on recent advances in light-driven iron catalysis in organic transformations, including iron/photoredox dual catalysis, light-induced iron photoredox catalysis and light-induced generation of active iron catalysts. The prospect for the future of this field is also discussed.
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BACKGROUND: Psychological stress can provoke and aggravate myocardial ischemia, and this stress can even trigger acute coronary syndromes or sudden cardiac death. Therefore, for the first time, this study aimed to investigate the method for establishing a rat model of myocardial ischemia with psychological stress and its evaluation. METHODS: Forty male Wistar rats were randomly divided into the sham (S, n=10), myocardial infarct (MI, n=10), psychological stress (MODEL, n=10), and myocardial infarct with psychological stress (MI + MODEL, n=10) groups. The rat model of psychological stress was established by measuring the data from activity restriction for 6 hours and followed by tail clamp stimulation for 5 minutes every day for 14 days. The rat model of the myocardial infarct with psychological stress was established by occluding the left coronary anterior descending artery in the MODEL rats. The body weight of rats was measured daily, the behavior parameters were evaluated via open-field test and elevated plus-maze, tongue color and sublingual vein were observed, rats' acral blood flow perfusion was detected by PIM II (Perfusion Imager II), mesenteric microcirculation was measured by capillaroscopy, and hemodynamics was measured by a polygraph system. An automatic biochemical analyzer determined the content of serum cTnT (cardiac troponin T), Hcy (homocysteine), and activity of LDH (lactate dehydrogenase). Myocardial infarct size was measured with TTC (triphenyhetrazolium chloride) staining. RESULTS: We found that rats in the psychological stress (MODEL) group were characterized by coarse hair, dark mucosa of the lips and claw, low spirit, decreased body weight, and increased anxiety. Compared with rats in the sham group, rats in the MODEL + MI group showed decreased mesenteric blood flow, narrowed arteriole and venule diameter, reduced acral blood flow perfusion, and LV ±dp/dtmax (the maximal rate of the increased and decrease of left ventricular pressure), as well as increased serum content of cTnT, Hcy, and LDH activity. Compared with the MI group, rats in the MODEL + MI group showed deteriorated microcirculation dysfunction manifested as a dark tongue color of deep purple, prominently extended and varicose sublingual vein, and aggravated myocardial damage in the form of increased infarct size and LDH leakage. CONCLUSIONS: In conclusion, the rat model of myocardial ischemia with psychological stress was successfully established, and manifested as aggravating behavioral disorder, mesenteric microcirculation and left ventricular dysfunction, and myocardial damage.
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The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD) and hyperlipidemia. Recent studies have uncovered the contribution of hormones, transcription factors, and inflammatory cytokines to the pathogenesis of dyslipidemia and fatty liver diseases. Moreover, a significant amount of effort has been put to examine the mechanisms underlying the potential therapeutic effects of many natural plant products on fatty liver diseases and metabolic diseases. We review the current understanding of insulin, thyroid hormone and inflammatory cytokines in regulating hepatic lipid metabolism, focusing on several essential transcription regulators, such as Sirtuins (SIRTs), Forkhead box O (FoxO), Sterol-regulatory element-binding proteins (SREBPs). We also discuss a few representative natural products with promising thereapeutic effects on fatty liver disease and dyslipidemia.
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Hígado Graso Alcohólico/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Fitoterapia , Alcaloides/farmacología , Animales , Citocinas/metabolismo , Dislipidemias , Flavonoides/farmacología , Factores de Transcripción Forkhead/metabolismo , Humanos , Insulina/metabolismo , Metabolismo de los Lípidos , Hígado/efectos de los fármacos , Saponinas/farmacología , Sirtuinas/metabolismo , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo , Hormonas Tiroideas/metabolismoAsunto(s)
Procedimientos Quirúrgicos del Sistema Biliar , Sistema Biliar/diagnóstico por imagen , Sistema Biliar/patología , Colangiografía , Cuidados Intraoperatorios , Hepatopatías/cirugía , Hígado/cirugía , Adulto , Anciano , Disección , Femenino , Arteria Hepática/cirugía , Humanos , Masculino , Persona de Mediana Edad , Vena Porta/cirugía , Resultado del TratamientoRESUMEN
Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone (abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mRNA and protein level of proinflammatory cytokines, IL-1ß, IL-6, TNF-α and iNOS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.
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Antiinflamatorios/uso terapéutico , Flavanonas/uso terapéutico , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Sepsis/tratamiento farmacológico , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Biomarcadores/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Células Cultivadas , Citocinas/metabolismo , Femenino , Flavanonas/química , Flavanonas/farmacología , Humanos , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Pulmón/patología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7 , Sepsis/inducido químicamente , Sepsis/metabolismo , Sepsis/patología , Transducción de Señal/efectos de los fármacos , Tasa de Supervivencia , Células THP-1 , Factor de Transcripción ReIA/metabolismo , Resultado del TratamientoRESUMEN
The rhythmic contraction of cardiomyocytes consumes a lot of energy. 90% of ATP in cardiomyocytes is produced by mitochondria. Maintenance of a healthy population of mitochondria by mitophagy is critical for cardiomyocyte survival and normal function. Mitophagy refers to selective removal of damaged mitochondria by autophagy mechanism. The process of mitophagy must be restricted to dysfunctional mitochondria and maintained at a balanced level. Disruption in the balance inevitably leads to cardiomyocyte injury and dysfunction. Accumulating evidence suggests that mitophagy plays a pivotal role in ischaemia/reperfusion-induced cardiomyocyte injury. In this review, we focus on the current understanding of mitophgy in cardiomyocyte function, the implications for cardiomyocyte injury in response to ischaemia/reperfusion as well as their underlying potential mechanisms.