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1.
Cardiovasc Res ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38626254

RESUMEN

AIM: The activation of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in endothelial cells (ECs) contributes to vascular inflammation in atherosclerosis. Considering the high glycolytic rate of ECs, we delineated whether and how glycolysis determines endothelial NLRP3 inflammasome activation in atherosclerosis. METHODS AND RESULTS: Our results demonstrated a significant upregulation of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), a key regulator of glycolysis, in human and mouse atherosclerotic endothelium, which positively correlated with NLRP3 levels. Atherosclerotic stimuli upregulated endothelial PFKFB3 expression via sterol regulatory element binding protein 2 (SREBP2) transactivation. EC-selective haplodeficiency of Pfkfb3 in Apoe-/- mice resulted in reduced endothelial NLRP3 inflammasome activation and attenuation of atherogenesis. Mechanistic investigations revealed that PFKFB3-driven glycolysis increased the NADH content and induced oligomerization of C-terminal binding protein 1 (CtBP1), an NADH-sensitive transcriptional co-repressor. The monomer form, but not the oligomer form, of CtBP1 was found to associate with the transcriptional repressor Forkhead box P1 (FOXP1) and acted as a transrepressor of inflammasome components, including NLRP3, caspase-1, and interleukin-1ß (IL-1ß). Interfering with NADH-induced CtBP1 oligomerization restored its binding to FOXP1 and inhibited the glycolysis-dependent upregulation of NLRP3, Caspase-1, and IL-1ß. Additionally, EC-specific overexpression of NADH-insensitive CtBP1 alleviates atherosclerosis. CONCLUSIONS: Our findings highlight the existence of a glycolysis-dependent NADH/CtBP/FOXP1-transrepression pathway that regulates endothelial NLRP3 inflammasome activation in atherogenesis. This pathway represents a potential target for selective PFKFB3 inhibitors or strategies aimed at disrupting CtBP1 oligomerization to modulate atherosclerosis.

2.
Sci Total Environ ; 927: 172379, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38614345

RESUMEN

Bisphenol S (BPS) is an alternative chemical to bisphenol A commonly used in food packaging materials. It raises concerns due to potential adverse effects on human health. However, limited evidence exists regarding reproductive toxicity from BPS exposure, and the mechanism of associated transgenerational toxicity remains unclear. In this study, pregnant SD rats were exposed to two different doses of BPS (0.05 or 20 mg/kg) from GD6 to PND21. The objective was to investigate reproductive and transmissible toxicity induced by BPS, explore endocrine effects, and uncover potential underlying mechanisms in rats. Perinatal exposure to BPS in the F0 generation significantly decreased the rate of body weight, ovarian organ coefficient, and growth and development of the F1 generation. Notably, these changes included abnormal increases in body weight and length, estrous cycle disruption, and embryonic dysplasia in F1. 4D-DIA proteomic and PRM analyses revealed that exposure to 20 mg/kg group significantly altered the expression of proteins, such as Lhcgr and Akr1c3, within the steroid biosynthetic pathway. This led to elevated levels of FSH and LH in the blood. The hypothalamic-pituitary-ovarian (HPO) axis, responsible for promoting fertility through the cyclic secretion of gonadotropins and steroid hormones, was affected. RT-qPCR and Western blot results demonstrated that the expression of GnRH in the hypothalamus was decreased, the GnRHR in the pituitary gland was decreased, and the expression of FSHß and LHß in the pituitary gland was increased. Overall, BPS exposure disrupts the HPO axis, hormone levels, and steroid biosynthesis in the ovaries, affecting offspring development and fertility. This study provides new insights into the potential effects of BPS exposure on the reproductive function of the body and its relevant mechanisms of action.


Asunto(s)
Disruptores Endocrinos , Fenoles , Ratas Sprague-Dawley , Reproducción , Sulfonas , Animales , Femenino , Fenoles/toxicidad , Ratas , Embarazo , Sulfonas/toxicidad , Reproducción/efectos de los fármacos , Disruptores Endocrinos/toxicidad , Efectos Tardíos de la Exposición Prenatal , Ovario/efectos de los fármacos
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 128-134, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38433642

RESUMEN

The sympathetic nervous system(SNS)plays a pivotal role in maintaining organ homeostasis and the pathogenesis of various ailments.Studies have unveiled a profound interconnection between sympathetic nerves and the development of liver cirrhosis,cirrhotic cardiomyopathy,and hepatorenal syndrome.Therefore,researchers have proposed SNS as a candidate therapeutic target for liver-related disorders.This article reviewed the research progress of sympathetic nerves in liver cirrhosis,cirrhotic cardiomyopathy,and hepatorenal syndrome,aiming to enrich the knowledge about the roles of sympathetic nerves in cirrhosis and its complications and provide new ideas for the treatment of liver cirrhosis and its complications.


Asunto(s)
Cardiomiopatías , Síndrome Hepatorrenal , Humanos , Cirrosis Hepática , Sistema Nervioso Simpático , Homeostasis
4.
J Gene Med ; 26(1): e3621, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37997255

RESUMEN

BACKGROUND: As the most prevalent primary brain tumor in adults, glioma accounts for the majority of all central nervous system malignant tumors. The concept of PANoptosis is a relatively new, underlining the interconnection and synergy among three distinct pathways: pyroptosis, apoptosis and necroptosis. METHODS: We performed single-cell annotations of glioma cells and determined crucial signaling pathways through cell chat analysis. Using least absolute shrinkage and selection operator (LASSO) and Cox analyses, we identified a gene set with prognostic values. Our model was validated using independent external cohort. In addition, we employed single-sample gene set enrichment analysis and xCell analyses to describe the detailed profile of infiltrated immune cells and depicted the gene mutation landscape in the two groups. RESULTS: We identified seven distinct cell clusters in glioma samples, including oligodendrocyte precursor cells (OPCs), myeloid cells, tumor cells, oligodendrocytes, astrocytes, vascular cells and neuronal cells. We found that myeloid cells showed the highest PANoptosis activity. An intense mutual cell communication pattern between the tumor cells and OPCs and oligodendrocytes was observed. Differentially expressed genes between the high-PANoptosis and low-PANoptosis cell groups were obtained, which were enriched to actin cytoskeleton, cell adhesion molecules and gamma R-mediated phagocytosis pathways. We determined a set of five genes of prognostic significance: SAA1, SLPI, DCX, S100A8 and TNR. The prognostic differences between the two groups in the internal and external sets were found to be statistically significant. We found a marked correlation between S100A8 and activated dendritic cell, macrophage, mast cell, myeloid derived suppressor cell and Treg infiltration. Moreover, we have observed a significant increase of PTEN mutation in the high risk (HR) group of glioma patients. CONCLUSIONS: In the present study, we have constructed a prognostic model that is based on the PANoptosis, and we have demonstrated its significant efficacy in stratifying patients with glioma. This innovative prognostic model offers novel insights into precision immune treatments that could be used to combat this disease and improve patient outcomes, thereby providing a new avenue for personalized treatment options.


Asunto(s)
Glioma , Multiómica , Adulto , Humanos , Apoptosis/genética , Expresión Génica , Glioma/genética
5.
J Hepatocell Carcinoma ; 10: 2305-2321, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38143910

RESUMEN

According to the Barcelona Clinic Liver Cancer (BCLC) system, radical resection of early stage primary hepatocellular carcinoma (HCC) mainly includes liver transplantation, surgical resection, and radiofrequency ablation (RFA), which yield 5-year survival rates of about 70-79%, 41.3-69.5%, and 40-70%, respectively. The tumor-free 5-year rate for HCC patients undergoing radical resection only reach up to 13.7 months, so the prevention of recurrence after radical resection of HCC is very important for the prognosis of patients. The traditional Chinese medicine (TCM) takes the approach of multitarget and overall-regulation to treat tumors, it can also independently present the "component-target-pathway" related to a particular disease, and its systematic and holistic characteristics can provide a personalized therapy based on symptoms of the patient by treating the patient as a whole. TCM as postoperative adjuvant therapy after radical resection of HCC in Barcelona Clinic liver cancer A or B stages, and the numerous clinical trials confirmed that the efficacy of TCM in the field of HCC has a significant effect, not only improving the prognosis and quality of life but also enhancing patient survival rate. However, with the characteristics of multi-target, multi-component, and multi-pathway, the specific mechanism of Chinese medicine in the treatment of diseases is still unclear. Because of the positive pharmacological activities of TCM in combating anti-tumors, the mechanism studies of TCM have demonstrated beneficial effects on the regulation of immune function, chronic inflammation, the proliferation and metastasis of liver cancer cells, autophagy, and cell signaling pathways related to liver cancer. Therefore, this article reviews the mechanism of traditional Chinese medicine in reducing the recurrence rate of HCC after radical resection.

6.
Polymers (Basel) ; 15(15)2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37571116

RESUMEN

Plant fiber-reinforced polylactic acid (PLA) exhibits excellent mechanical properties and environmental friendliness and, therefore, has a wide range of applications. This study investigated the mechanical properties of three short plant fiber-reinforced PLA composites (flax, jute, and ramie) using mechanical testing and material characterization techniques (SEM, FTIR, and DSC). Additionally, we propose a methodology for predicting the mechanical properties of high-content short plant fiber-reinforced composite materials. Results indicate that flax fibers provide the optimal reinforcement effect due to differences in fiber composition and microstructure. Surface pretreatment of the fibers using alkali and silane coupling agents increases the fiber-matrix interface contact area, improves interface performance, and effectively enhances the mechanical properties of the composite. The mechanical properties of the composites increase with increasing fiber content, reaching the highest value at 40%, which is 38.79% higher than pure PLA. However, further increases in content lead to fiber agglomeration and decreased composite properties. When the content is relatively low (10%), the mechanical properties are degraded because of internal defects in the material, which is 40.42% lower than pure PLA. Through Micro-CT technology, the fiber was reconstructed, and it was found that the fiber was distributed mainly along the direction of injection molding, and the twin-screw process changes the shape and length of the fiber. By introducing the fiber agglomeration factor function and correcting the Halpin-Tsai criterion, the mechanical properties of composite materials with different contents were successfully predicted. Considering the complex stress state of composite materials in actual service processes, a numerical simulation method was established based on transversely isotropic material using the finite element method combined with theoretical analysis. The mechanical properties of high-content short plant fiber-reinforced composite materials were successfully predicted, and the simulation results showed strong agreement with the experimental results.

7.
Nat Commun ; 14(1): 3216, 2023 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-37270581

RESUMEN

Although the power conversion efficiency values of perovskite solar cells continue to be refreshed, it is still far from the theoretical Shockley-Queisser limit. Two major issues need to be addressed, including disorder crystallization of perovskite and unbalanced interface charge extraction, which limit further improvements in device efficiency. Herein, we develop a thermally polymerized additive as the polymer template in the perovskite film, which can form monolithic perovskite grain and a unique "Mortise-Tenon" structure after spin-coating hole-transport layer. Importantly, the suppressed non-radiative recombination and balanced interface charge extraction benefit from high-quality perovskite crystals and Mortise-Tenon structure, resulting in enhanced open-circuit voltage and fill-factor of the device. The PSCs achieve certified efficiency of 24.55% and maintain >95% initial efficiency over 1100 h in accordance with the ISOS-L-2 protocol, as well as excellent endurance according to the ISOS-D-3 accelerated aging test.

8.
Phys Chem Chem Phys ; 25(19): 13673-13682, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37158005

RESUMEN

The understanding of the interfacial effect on charge transport is essential in single-molecule electronics. In this study, we elucidated the transport properties of molecular junctions comprising thiol-terminated oligosilane with three to eight Si atoms and two types of Ag/Au electrode materials employing different interfacial configurations. First-principles quantum transport calculations demonstrated that the interfacial configuration determines the relative magnitude of the current between the Ag and Au electrodes, wherein the Ag monoatomic contact configuration presented a larger current than did the Au double-atom configuration. Further, the mechanism of electron tunneling from the interfacial states through the central σ channel was revealed. In contrast to Au double-atom electrodes, Ag monoatomic electrodes exhibit a higher current due to the presence of Ag-S interfacial states closer to the Fermi level. Our findings show that the interfacial configuration is a plausible way to generate the relative magnitude of current of thiol-terminated oligosilane molecular junctions with Au/Ag electrodes and provide further insight into the interfacial effect on the transport properties.

9.
N Engl J Med ; 388(22): 2025-2036, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37256974

RESUMEN

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).


Asunto(s)
Fibrinolíticos , Accidente Cerebrovascular Isquémico , Tirofibán , Humanos , Aspirina/efectos adversos , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/etiología , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Hemorragias Intracraneales/inducido químicamente , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tirofibán/efectos adversos , Tirofibán/uso terapéutico , Resultado del Tratamiento , Enfermedades Arteriales Cerebrales/tratamiento farmacológico , Enfermedades Arteriales Cerebrales/etiología
10.
Interv Neuroradiol ; : 15910199231151275, 2023 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-36703568

RESUMEN

BACKGROUND: To quantify the effectiveness and safety of the Trevo® Retriever for endovascular treatment of acute ischemic stroke (AIS) patients in China. METHODS: Trevo Retriever Registry (China) was a prospective, multicenter, non-comparative, open-label study of patients with AIS treated with the Trevo Retriever. The primary outcome was the proportion of patients achieving an expanded Thrombolysis in Cerebral Infarction (eTICI) score ≥2b at the end of endovascular treatment. Secondary outcomes included first-pass eTICI score ≥2b and 90-day modified Rankin Scale (mRS) score ≤2. RESULTS: The Trevo Retriever Registry (China) enrolled and followed 201 patients (62.1 ± 12.5 years-old; 70.6% male) at 11 centers. The pre-procedure NIHSS score and ASPECTS were 16 (interquartile range (IQR), 13-21) and 7 (IQR, 6-9), respectively, and 188 (93.5%) patients had an mRS score of 0 prior to the stroke. The main stroke etiology was large artery atherosclerosis, accounting for 71.6% (144/201) of patients. Post-procedure eTICI ≥2b was 98.4% (187/190). First-pass eTICI ≥2b was 74.7% (136/182). The 90-day good outcome (mRS ≤2) rate was 73.6% (148/201). The 90-day all-cause mortality was 5.5% (11/201). Neurological deterioration at 24 h post-procedure was observed in 7.7% (15/195) patients. Embolism in a new territory was seen in one patient (0.5%). Two (1.0%) procedure-related adverse events (AEs) occurred, which were intra-procedure cerebral artery embolism. No Trevo related AEs occurred. CONCLUSIONS: This real-world study of the Trevo Retriever in China demonstrated a high rate of revascularization and first-pass success that resulted in an overall high good function outcome rate and low mortality.

11.
Front Microbiol ; 14: 1302775, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38173676

RESUMEN

Nitrogen (N) as an essential macronutrient affects the soil nutrient cycle, microbial community abundance, and metabolic function. However, the specific responses of microorganisms and metabolic functions in rhizosphere soil of Phellodendron chinense Schneid seedlings to N addition remain unclear. In this study, four treatments (CK, N5, N10 and N15) were conducted, and the soil physicochemical properties, enzyme activities, microbial community abundances and diversities, metabolism, and gene expressions were investigated in rhizosphere soil of P. chinense Schneid. The results showed that N addition significantly decreased rhizosphere soil pH, among which the effect of N10 treatment was better. N10 treatment significantly increased the contents of available phosphorus (AP), available potassium (AK), ammonium nitrogen (NH4+-N), nitrate nitrogen (NO3--N) and sucrase (SU) activity, as well as fungal diversity and the relative expression abundances of amoA and phoD genes in rhizosphere soil, but observably decreased the total phosphorus (TP) content, urease (UR) activity and bacterial diversity, among which the pH, soil organic matter (SOM), AP, NH4+-N and NO3--N were the main environmental factors for affecting rhizosphere soil microbial community structure based on RDA and correlation analyses. Meanwhile, N10 treatment notably enhanced the absolute abundances of the uracil, guanine, indole, prostaglandin F2α and γ-glutamylalanine, while reduced the contents of D-phenylalanine and phenylacetylglycine in rhizosphere soil of P. chinense Schneid seedlings. Furthermore, the soil available nutrients represented a significant correlation with soil metabolites and dominant microorganisms, suggesting that N10 addition effectively regulated microbial community abundance and metabolic functions by enhancing nutrient cycle in the rhizosphere soil of P. chinense Schneid seedlings.

12.
Sci Rep ; 12(1): 18300, 2022 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-36316417

RESUMEN

A considerable number of studies have described the potential neural mechanism of deception, but most deception studies have relied upon deception from experimental supervisor instruction. Experimental control (participants follow instructions to deceive without any risk) means that the deception occurs in a way that does not come close to the real deception. In the current study, a neural imaging experiment on deception closer to the real deception was conducted. Event-related potential (ERP) and event-related spectral perturbation (ERSP) techniques were used to explore the neural mechanism of deception. The results showed that deceptive response evoked larger medial-frontal negativity (MFN) and smaller response-locked positivity (RLP) than truthful response. We interpret these findings to indicate that conflict detection and emotional processing are associated with deception. In addition, magnitudes of alpha and beta oscillations after the deceptive response were significantly smaller than those after the truthful response, demonstrating that deception is associated with neural oscillations reflecting conflict adjustment. The results comprehensively characterized the physiological properties of the brain oscillations elicited by a deceptive response and provided a theoretical foundation for detection in practical applications.


Asunto(s)
Decepción , Potenciales Evocados , Humanos , Tiempo de Reacción/fisiología , Potenciales Evocados/fisiología , Mapeo Encefálico , Encéfalo/fisiología
13.
Front Pharmacol ; 13: 1032282, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36339551

RESUMEN

Background: Paeoniflorin (PF) is the main active component of Chinese herbaceous peony that has been shown to have an anti-tumor effect. However, there are few studies on the prevention and treatment of pancreatic cancer with PF. Methods: We gathered Microarray data pertaining to paeoniflorin intervention in pancreatic cancer by utilizing the GEO database (GSE97124). Then, the DEGs were filtered by the 33R program. RNA-seq data of pancreatic cancer and normal tissue samples were taken from the TCGA and GTEx databases, respectively, and the WGCNA technique was utilized to examine the pancreatic cancer-specific genes. Paeoniflorin target genes for the treatment of pancreatic cancer were determined based on the overlap between DEGs and WGCNA. GO and KEGG enrichment analyses were then performed on paeoniflorin target genes to discover which biological processes were impacted. Using the 3 hierarchical methods included in the Cytohubba plugin, we re-screened the hub genes in the target genes to find the genes most relevant to paeoniflorin treatment. The overall survival effects of hub genes were confirmed using the TCGA database. Finally, the paeoniflorin targets identified by the network pharmacology analysis were validated using PANC-1 and Capan-2 cells. Results: We identified 148 main potential PF targets, and gene enrichment analysis suggested that the aforementioned targets play a crucial role in the regulation of MAPK, PI3K-AKT, and other pathways. The further screening of the prospective targets resulted in the identification of 39 hub genes. Using the TCGA database, it was determined that around 33.33% of the hub gene's high expression was linked with a bad prognosis. Finally, we demonstrated that PF inhibits IL-6 and IL-10 expression and p38 phosphorylation in pancreatic cancer cells, thereby reducing inflammation. Conclusion: PF may regulate inflammatory factors mainly through the p38 MAPK signal pathway. These findings provide theoretical and experimental evidence suggesting the PF as a promising natural source of anti-tumor compounds for pancreatic cancer.

14.
Langmuir ; 38(23): 7225-7233, 2022 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-35653608

RESUMEN

A low-dimensional organic amine lead halide perovskite is an attractive semiconductor material that has potential application prospects in photovoltaics, light-emitting diodes, detectors, X-ray imaging, and other fields. It has been reported that the photoelectric properties of low-dimensional perovskite can be controlled by adjusting the chain length of organic ammonium, the ratio of precursor components, and van der Waals interaction between amine molecules. Herein, we report the successful synthesis of low-dimensional perovskite (PdEA)PbI4 (PdEA = piperidine ethylammonium) and (MlEA)PbI4 (MlEA = morpholine ethylammonium) single crystals by regulating the intermolecular hydrogen bond of organic ammonium ligands. The two-dimensional (2D) layered structure (PdEA)PbI4 single crystal with a fluorescence reflection peak at 563 nm was produced by the reaction of PdEA with PbO in a concentrated hydroiodic acid aqueous solution. Differently, the (MlEA)PbI4 single crystal prepared by replacing MlEA with PdEA presents a one-dimensional (1D) rod structure, and its fluorescence reflection peak is located at 531 nm. The optical bandgaps of (PdEA)PbI4 and (MlEA)PbI4 perovskite films were about 2.16 and 2.33 eV, respectively. Low-dimensional perovskite solar cells with 2D (PdEA)PbI4 and 1D (MlEA)PbI4 of perovskite films yielded efficiencies of 1.18 and 1.52%, respectively.

15.
Pharmacol Res ; 179: 106208, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35398239

RESUMEN

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells which are immunosuppressive and glycolytically inactive in inflammatory diseases. However, it is unknown whether MDSCs contribute to ischemic stroke and how glycolysis regulates MDSC function in such a context. Here, we showed that MDSCs arise in the blood of patients at early phase of stroke. Similar results were observed in temporary middle cerebral artery occlusion-induced cerebral ischemic mice. Pharmaceutical exhaustion of MDSCs aggravated, while adoptive transfer of MDSCs rescued the ischemic brain injury. However, the differentiation of MDSCs into immunopotent myeloid cells which coincides with increased glycolysis was observed in the context of ischemic stroke. Mechanistically, the glycolytic product lactate autonomously induces MDSC differentiation through activation of mTORC1, and paracrinely activates Th1 and Th17 cells. Moreover, gene knockout or inhibition of the glycolytic enzyme PFKFB3 increased endogenous MDSCs by blocking their differentiation, and improved ischemic brain injury. Collectively, these results revealed that glycolytic switch decreases the immunosuppressive and neuroprotective role of MDSCs in ischemic stroke and pharmacological targeting MDSCs via glycolysis inhibition constitutes a promising therapeutic strategy for ischemic stroke.


Asunto(s)
Lesiones Encefálicas , Accidente Cerebrovascular Isquémico , Células Supresoras de Origen Mieloide , Animales , Glucólisis , Humanos , Inmunosupresores , Ratones , Ratones Endogámicos C57BL
16.
Zhen Ci Yan Jiu ; 47(1): 27-32, 2022 Jan 25.
Artículo en Chino | MEDLINE | ID: mdl-35128867

RESUMEN

OBJECTIVE: To observe the effect of electroacupuncture(EA) on glucagon-like peptide-1 receptor (GLP-1R)/ phosphatidylinositol 3-kinase (PI3K)/ protein kinase B(Akt) protein pathway in the substantia nigra of mice with Parkinson's di-sease (PD),so as to explore its underlying mechanisms in treatment of PD. METHODS: Forty-eight C57BL/6 male mice were randomly divided into normal, model, EA and inhibitor groups, with 12 mice in each group. PD mouse model was established by intragastrical administration of rotenone for 4 weeks. In the EA group, EA was applied at "Fengfu"(GV16), "Taichong"(LR3) and"Zusanli"(ST36) for 30 min, once daily, for 2 weeks. The mice of the inhibitor group received gavage of dipeptidyl peptidase-4 inhibitor ligliptin (10 mg·kg-1·d-1) once a day for 2 weeks. The behavioral scores of mice in each group were observed. The levels of tyrosine hydroxylase (TH) in serum and substantia nigra were detected by ELISA, and the protein relative expression levels of GLP-1R, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) in substantia nigra of midbrain of mice were detected by Western blot. RESULTS: Compared with the normal group, the behavioral scores were significantly increased (P<0.01), TH levels in serum and substantia nigra, protein expression levels of GLP-1R, p-PI3K and p-Akt of the substantia nigra in the model group were significantly decreased (all P<0.01). After intervention and in comparison with the model group, the behavioral scores were significantly decreased (P<0.01), TH levels and the protein expression levels of GLP-1R, p-PI3K and p-Akt in both EA and inhibitor groups were significantly increased (all P<0.01). There were no significant differences in the abovementioned indexes between EA group and inhibitor group (all P>0.05), except for TH levels which were considerably down-regulated in the EA group relative to the inhibitor group (P<0.01, P<0.05). CONCLUSION: EA at GV16, LR3 and ST36 may increase the level of TH in serum and substantia nigra by up-regulating the activity of GLP-1R/PI3K/Akt protein pathway, and improve the behavioral performance of PD induced by rotenone.


Asunto(s)
Electroacupuntura , Enfermedad de Parkinson , Animales , Receptor del Péptido 1 Similar al Glucagón , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapia , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Ratas Sprague-Dawley
17.
J Colloid Interface Sci ; 607(Pt 2): 1083-1090, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34583030

RESUMEN

Selective ultraviolet-harvesting transparent perovskite solar cells (T-PSCs) have attracted great interest because of their high transmittance and unique photovoltaic properties, especially in the fields of smart windows for power generation and building glass. However, owing to the unsatisfactory solubility of PbCl2 in most conventional solvents, preparing transparent methylammonium lead chloride (MAPbCl3) films with high quality and sufficient thickness by conventional methods poses a substantial challenge for their application deployment in T-PSCs. In this work, two novel strategies based on an ion-exchange procedure for controlling phase transition engineering (CPTE) are proposed. For CPTE-2, an optimized cubic phase MAPbCl3 film with a large grain size and high full coverage is prepared by transforming the tetragonal phase MAPbI3 precursor into the cubic phase MAPbCl3. Establishing relevant models based on crystal parameters investigates the formation mechanism of this high-quality MAPbCl3 film. Accordingly, the resultant T-PSCs exhibit remarkable film quality and micron-sized grains and reach an optimum efficiency of 0.33% (JSC = 0.66 mA cm-2, VOC = 1.14 V, and FF = 43.72%).

18.
Zhongguo Zhen Jiu ; 40(10): 1047-51, 2020 Oct 12.
Artículo en Chino | MEDLINE | ID: mdl-33068344

RESUMEN

OBJECTIVE: To compare the immediate effect of acupuncture and moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) on heart rate variability index in patients with qi deficiency syndrome. METHODS: Ninety patients with qi deficiency syndrome were randomly divided into an acupuncture group, a moxibustion group and a blank group, 30 patients in each group. The patients in the acupuncture group were treated with acupuncture at Guanyuan (CV 4) and Zusanli (ST 36) for 15 min; acupuncture was given once. The patients in the moxibustion group were treated with moxibustion with identical acupoints and treatment duration. The patients in the blank group received no intervention. The symptom scores of qi deficiency syndrome in each group before and after treatment were recorded. The average heart rate and index of heart rate variability including total power, low frequency (LF), high frequency (HF) and logarithm of LF/HF (log LF/HF) were tested 5 min before treatment, 5 min, 10 min, 15 min into treatment, and 5 min after treatment. RESULTS: The symptom scores of qi deficiency syndrome were reduced in the acupuncture group and moxibustion group after treatment (P<0.05). Compared before treatment, in the acupuncture group, the HF was increased 5 min into treatment (P<0.05), but was reduced 15 min into treatment and 5 min after treatment (P<0.05, P<0.01). The log LF/HF was increased 5 min and 10 min into treatment and 5 min after treatment (P<0.01). The difference of average heart rate between 5 min before treatment and 5 min after treatment in the acupuncture group was higher than that in the moxibustion group and blank group (P<0.05), and the difference of log LF/HF was higher than that in the moxibustion group and blank group (P<0.05, P<0.01). CONCLUSION: Acupuncture and moxibustion has immediate effects on heart rate variability in patients with qi deficiency syndrome, and the effect of acupuncture is superior to moxibustion, which may be related to the benign regulation of acupuncture on autonomic nervous system.


Asunto(s)
Terapia por Acupuntura , Frecuencia Cardíaca , Moxibustión , Qi , Puntos de Acupuntura , Humanos , Medicina Tradicional China , Síndrome
19.
Environ Sci Pollut Res Int ; 27(21): 25908-25924, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31832961

RESUMEN

In this study, nutrient and heavy metal contamination in surface sediments of the Xiashan stream were investigated. Determining pollution degree of nutrient and heavy metal were the main objectives of this investigation. For this reason, the concentrations of total nitrogen (TN), total phosphorus (TP), seven heavy metals (Cu, Zn, Pb, Cd, Cr, Ni, Hg), and metalloid (As) were analyzed at 55 sampling sites. The mean TN concentration in surface sediments was 5.007 g/kg, while the mean TP concentration was 0.385 g/kg. Based on the sediment quality guideline (SQGs) and background values of Chinese soil and sediment, the majority of the mean TN concentrations in surface sediments were higher than their background values, while the TP concentrations were different from those observed for TN. For heavy metal concentrations in surface sediments, most of sampling stations were higher than their background values. The mean geo-accumulation (Igeo) indices for heavy metals were ranked as follows: Cd > Hg > Cu > Zn > Pb > Ni > Cr > As. The potential ecological risk index (RI) indicated heavy metal contamination level in Xiashan stream was very high ecological risk. According to Igeo and RI values, heavy metals especially Cd and Hg are influenced significantly by anthropogenic activities. Cd and Hg are not only as pollutant but also considerable contributor to ecological risk. Multivariate statistical investigations showed that there is a significant and positive correlation between Pb, As, and Cd. Cu, Ni, and Cr have similar characteristic and therefore probably originated from the same sources. Suggested by the results, it is necessary to control nitrogen and heavy metal contamination caused by human activities in the study area.


Asunto(s)
Metales Pesados/análisis , Contaminantes Químicos del Agua/análisis , China , Monitoreo del Ambiente , Sedimentos Geológicos , Humanos , Nutrientes , Medición de Riesgo , Ríos
20.
Biosci Rep ; 39(5)2019 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-31015365

RESUMEN

Glioblastoma multiform is the most common and malignant primary tumor of the central nervous system in adults, the high recurrence rate and poor prognosis are critical priorities. Pristimerin is a naturally occurring quinone methide triterpenoid isolated from the Celastraceae and Hippocrateaceae families. Its anticancer effects have garnered considerable attention; nonetheless, the mechanisms of action remain unknown. To predict the hub genes of pristimerin, PharmMapper and the Coremine database were used to identify 13 potential protein targets; protein-protein interaction, for which functional enrichment analyses were performed. Compound-target, target-pathway, and compound-target-pathway networks were constructed using Cytoscape. Biological process analysis first revealed that enrichment of these target genes correlated with negative regulation of symbiont growth in the host, and regulation of chronic inflammatory response to antigenic stimulus. Survival analysis in cBioPortal showed that protein tyrosine phosphatase, non-receptor type 1 (PTPN1) and Argonaute 2 (AGO2) might be involved in the carcinogenesis, invasion, or recurrence of diffuse glioma. In addition, we observed that low-dose pristimerin inhibited the viability of glioma cells, while miR-542-5p in vitro; and reduced PTPN1 expression. Notably, high-dose pristimerin induced apoptosis. Furthermore, miR-542-5p silence with siRNA in glioma cells lead to the elevation in AGO2, and decreased PTPN1 level. The effect was obviously post pristimerin treatment and miR-542-5p suppression. In conclusion, pristimerin inhibited glioma progression through AGO2 and PTPN1 expression via a canonical miRNA-mediated mechanism.


Asunto(s)
Antineoplásicos/farmacología , Proteínas Argonautas/genética , Glioblastoma/tratamiento farmacológico , MicroARNs/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 1/genética , Triterpenos/farmacología , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/genética , Glioblastoma/patología , Humanos , Ratones , Triterpenos Pentacíclicos
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