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1.
J Biochem Mol Toxicol ; 38(1): e23519, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37665680

RESUMEN

Immunotherapy has developed rapidly in recent years. This study aimed to establish a prognostic signature for immune-related genes (IRGs) and explore related potential immunotherapies. The RNA-seq transcriptome profiles and clinicopathological information of patients were obtained from The Cancer Genome Atlas. Differentially expressed IRGs in tumors and normal tissues were screened and a risk score signature was constructed to predict the prognosis in patients with hepatocellular carcinoma (HCC). Receiver operating characteristic curves, survival analyses, and correlation analyses were used to explore the clinical application of this model. We further analyzed the differences in clinical characteristics, immune infiltration, somatic mutations, and treatment sensitivity between the high- and low-risk populations characterized by the prognostic models. The immune cell infiltration score and immune-related pathway activity were calculated using the single sample gene set enrichment analysis (ssGSEA) set enrichment analysis. Gene ontology (GO), Kyoto encyclopedia of genes and genomes, and GSEA were used to explore the underlying mechanisms. We constructed a nine-IRG formula to predict the prognosis in HCC patients. The higher the risk score, the higher the malignancy of the tumor and the worse the prognosis. There were significant differences in immune related processes between the high- and low-risk groups. TP53 and CTNNB1 mutations were significantly different between different risk groups. The expression of model gene was closely related to the sensitivity of tumor cells to chemotherapeutic drugs. This risk score model, which is helpful for the individualized treatment of patients with different risk factors, could be a reliable prognostic tool for HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Factores de Riesgo , Expresión Génica , Ontología de Genes
2.
Int J Mol Sci ; 25(7)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38612395

RESUMEN

Originally discovered in C. elegans, LIN28 is an evolutionarily conserved zinc finger RNA-binding protein (RBP) that post-transcriptionally regulates genes involved in developmental timing, stem cell programming, and oncogenesis. LIN28 acts via two distinct mechanisms. It blocks the biogenesis of the lethal-7 (let-7) microRNA (miRNA) family, and also directly binds messenger RNA (mRNA) targets, such as IGF-2 mRNA, and alters downstream splicing and translation events. This review focuses on the molecular mechanism of LIN28 repression of let-7 and current strategies to overcome this blockade for the purpose of cancer therapy. We highlight the value of the LIN28/let-7 pathway as a drug target, as multiple oncogenic proteins that the pathway regulates are considered undruggable due to their inaccessible cellular location and lack of cavities for small molecule binding.


Asunto(s)
MicroARNs , Animales , Caenorhabditis elegans/genética , Carcinogénesis , Transformación Celular Neoplásica , MicroARNs/genética , ARN Mensajero , Humanos
3.
Inorg Chem ; 62(23): 9005-9013, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37252689

RESUMEN

Manipulating the interfacial/surface structure of ligand-stabilized atomically precise metal nanoclusters (NCs) is one of the central tasks in nanoscience because surface motifs are directly related to key properties of nanomaterials. Although great progress has been made in engineering the surface of gold and silver nanoclusters, parallel studies on lighter copper analogues hitherto remain unexplored. In this work, we report the design, synthesis, and structure of a new class of copper nanoclusters featuring virtually identical kernels but different surface motifs. The four Cu29 nanoclusters share the same Cu13 kernel with unprecedented anticuboctahedral architecture. Finely modulating synthetic parameters endows the Cu13 core with diverse surface structures, thus affording the Cu29 series with labile surface coatings. More interestingly, the slight surface modification results in distinct optical and catalytic properties of the cluster compounds, highlighting the importance of the surface structure in shaping the behaviors of copper nanomolecules. This work not only exemplifies the efficiency of surface engineering for controlling properties of well-defined copper nanoclusters but also provides a new family of Cu materials with a clear molecular structure and controlled surface motifs that hold great promise in studying structure-property relationships.

4.
J Gastroenterol Hepatol ; 38(11): 1942-1948, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37403267

RESUMEN

BACKGROUND AND AIM: The relationship between Helicobacter pylori (H. pylori) and fast plasma glucose (FPG) on nondiabetes populations is still inconclusive. Nowadays, not only the high infection rate of H. pylori but also the high FPG level is threatening the Chinese people. METHODS: A retrospective cohort study has been established to analyze the relationship between H. pylori infection and FPG level, 18 164 individuals performed healthy examination in Taizhou Hospital Health Examination Center from 2017 to 2022 were included, and hematological indicators, body parameters, and H. pylori detection by 13 C-urea breath test were collected from patients. The follow-up intervals were greater than 12 months. RESULTS: H. pylori infection was regarded as an independent risk factor for elevated FPG after multivariate logistic regression. Additionally, the average interval time were 33.6 ± 13.3 months. Mean changed FPG values in the persistent infection group were higher than in the subgroup of persistent negative (P = 0.029) as well as eradication infection (P = 0.007). The aforementioned changes began to appear after 2 years of follow-up. Similarly, when compared with the subgroup of persistent infection, mean changed triglyceride/high density lipoprotein (TG/HDL) values were much lower in the subgroup of persistent negative (P = 0.008) and eradication infection (P = 0.018), but the differences appeared after 3 years of follow-up. CONCLUSIONS: H. pylori infection is an independent risk factor for elevated FPG in non-diabetes mellitus (DM) individuals. Persistent H. pylori infection causes an increase in FPG level and TG/HDL, which may be a risk factor for diabetes mellitus.


Asunto(s)
Diabetes Mellitus , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Glucemia , Estudios Retrospectivos , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/diagnóstico , Pueblos del Este de Asia , Infección Persistente , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Triglicéridos , Ayuno
5.
Phys Chem Chem Phys ; 25(28): 18866-18873, 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37403608

RESUMEN

Monoclinic bismuth vanadate (BiVO4) has emerged as an excellent optically active photoanode material due to its unique physical and chemical properties. Experiments reported that the low concentration of oxygen vacancies enhances the photoelectrochemical (PEC) activity of BiVO4, but the high concentration of oxygen vacancies decreases the charge carrier lifetime. Using time-domain density functional theory and molecular dynamics, we have demonstrated that the distribution of oxygen vacancies has strong effects on the static electronic structure and nonadiabatic (NA) coupling of the BiVO4 photoanode. The localized oxygen vacancies create charge recombination centers within the band gap and enhance the NA coupling between the VBM and the CBM, resulting in fast charge and energy losses. By contrast, the discrete oxygen vacancies can eliminate the charge recombination centers and decrease the NA coupling between the VBM and the CBM, enhancing the PEC activity of monoclinic BiVO4. Our study suggests that the PEC performance of a photoanode can be improved by changing the distribution of oxygen vacancies.

6.
Phys Chem Chem Phys ; 25(47): 32622-32631, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38009229

RESUMEN

By performing nonadiabatic molecular dynamics combined with ab initio time-domain density functional theory, we have explored the effects of the charge density of a sulfur vacancy on charge trapping and recombination in antimony trisulfide (Sb2S3). The simulations demonstrate that, compared to an antimony vacancy, the sulfur vacancy generates a high charge density trap state within the band gap. This state acts as the recombination center and provides new channels for charge carrier relaxation. Filling the sulfur vacancy with electron donors elevates the defect state to the Fermi level due to the introduced extra electrons. In contrast, the electron acceptor lowers the charge density of the sulfur vacancy by capturing its local electrons, eliminating the charge recombination center and extending the photo-generated charge carrier lifetime. Additionally, compared with electron injection, hole injection can also decrease the charge density of the trap state via neutralizing its local electronic states, eliminate the trap state within the band gap, and suppress nonradiative electron-hole recombination. This study is expected to shed new light on the blocking recombination centers and provide valuable insights into the design of high-performance solar cells.

7.
Immunopharmacol Immunotoxicol ; 45(5): 539-548, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36891829

RESUMEN

The A20 protein is considered to have a potent anti-inflammatory effect, but its mechanism of action in the regulation of ferroptosis and inflammation after stroke is still unknown. In this study, the A20-knockdown BV2 cell line (sh-A20 BV2) was constructed at first, and the oxygen-glucose deprivation/re-oxygenation (OGD/R) cell model was constructed. Both the BV2 and sh-A20 BV2 cells were treated with the ferroptosis inducer erastin for 48 h, the ferroptosis-related indicators were detected by western blot. The mechanism of ferroptosis was explored by western blot and immunofluorescence. Under OGD/R pressure, the oxidative stress level of sh-A20 BV2 cells was inhibited, but the secretion of the inflammatory factors TNF-α, IL-1ß, and IL-6 was significantly upregulated. And sh-A20 BV2 cells had higher expression levels of GPX4 and NLRP3 proteins under OGD/R induction. Western blot further confirmed that sh-A20 BV2 cells inhibited OGD/R-induced ferroptosis. Under the effect of erastin of the ferroptosis inducer (0-1000 nM), sh-A20 BV2 cells had higher cell viability than wild-type BV2 cells and significantly inhibited the accumulation of ROS and the level of oxidative stress damage. It was confirmed that A20 could promote the activation of the IκBα/NFκB/iNOS pathway. It was confirmed by an iNOS inhibitor that iNOS inhibition could reverse the resistance effect of BV2 cells to OGD/R-induced ferroptosis after A20 knockdown. In conclusion, this study demonstrated that inhibition of A20 mediates a stronger inflammatory response while enhancing microglial resistance by knocking down A20 in BV2 cells.


Asunto(s)
Ferroptosis , Accidente Cerebrovascular , Humanos , Microglía/metabolismo , FN-kappa B/metabolismo , Línea Celular
8.
Inorg Chem ; 60(7): 4362-4365, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33761738

RESUMEN

By employment of a mixed truncated chiral ligand synthetic strategy, a defect-engineered chiral metal-organic framework with hierarchical micro/mesoporous structure was prepared, and it exhibited efficient heterogeneous catalytic activity and enantioselectivity for asymmetric aldol reaction.

9.
Inorg Chem ; 57(14): 8033-8036, 2018 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-29956541

RESUMEN

The Brønsted basicity in activated metal-organic framework-808 (hereinafter denoted as MOF-808a) was confirmed by the analyses of CO2-TPD-MS, in situ DRIFTS, and acid-base titration. MOF-808a exhibited efficient recyclable catalytic activities for Heck coupling and oxidation of alcohol as a one-pot tandem reaction in base-free catalysis. It is the first evidence of the Brønsted basicity in zirconium metal-organic frameworks (Zr-MOFs) and gave rise to a new opportunity to extend the catalytic application of Zr-MOFs.

10.
PLoS Genet ; 11(12): e1005726, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26710269

RESUMEN

Accumulated evidence demonstrated that long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis. However, it is still largely unknown how these lncRNAs were regulated by small ncRNAs, such as microRNAs (miRNAs), at the post-transcriptional level. We here use lncRNA HOTTIP as an example to study how miRNAs impact lncRNAs expression and its biological significance in hepatocellular carcinoma (HCC). LncRNA HOTTIP is a vital oncogene in HCC, one of the deadliest cancers worldwide. In the current study, we identified miR-192 and miR-204 as two microRNAs (miRNAs) suppressing HOTTIP expression via the Argonaute 2 (AGO2)-mediated RNA interference (RNAi) pathway in HCC. Interaction between miR-192 or miR-204 and HOTTIP were further confirmed using dual luciferase reporter gene assays. Consistent with this notion, a significant negative correlation between these miRNAs and HOTTIP exists in HCC tissue specimens. Interestingly, the dysregulation of the three ncRNAs was associated with overall survival of HCC patients. In addition, the posttranscriptional silencing of HOTTIP by miR-192, miR-204 or HOTTIP siRNAs could significantly suppress viability of HCC cells. On the contrary, antagonizing endogenous miR-192 or miR-204 led to increased HOTTIP expression and stimulated cell proliferation. In vivo mouse xenograft model also support the tumor suppressor role of both miRNAs. Besides the known targets (multiple 5' end HOX A genes, i.e. HOXA13), glutaminase (GLS1) was identified as a potential downstream target of the miR-192/-204-HOTTIP axis in HCC. Considering glutaminolysis as a crucial hallmark of cancer cells and significantly inhibited cell viability after silencingGLS1, we speculate that the miR-192/-204-HOTTIP axis may interrupt HCC glutaminolysis through GLS1 inhibition. These results elucidate that the miR-192/-204-HOTTIP axis might be an important molecular pathway during hepatic cell tumorigenesis. Our data in clinical HCC samples highlight miR-192, miR-204 and HOTTIP with prognostic and potentially therapeutic implications.


Asunto(s)
Carcinoma Hepatocelular/genética , Glutaminasa/metabolismo , Neoplasias Hepáticas/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Animales , Proteínas Argonautas/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Femenino , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Persona de Mediana Edad
11.
Molecules ; 23(12)2018 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-30487451

RESUMEN

The 1,3,6,8-tetrabromocarbazole and 3-bromocarbazole have attracted great attention in the ecotoxicology field recently as hazardous environmental contaminants. In this study, the quenching mechanism of these two substances binding with human serum albumin (HSA) has been investigated with spectroscopic methods. Through fluorescence quenching and binding site experiments with steady-state fluorescence and UV-Vis spectra, the intrinsic fluorescence of HSA quenched by 1,3,6,8-tetrabromocarbazole and 3-bromocarbazole both in static process, are activated by binding to site II (subdomain IIIA) of the HSA. In addition, it was not only found that the conformation and secondary structure of the proteins changes, but also that their spontaneous binding processes were driven by electrostatic interactions as well as hydrophobic forces for HSA-1,3,6,8-tetrabromocarbazole, and by typical hydrophobic forces for HSA-3-bromocarbazole. The above studies are beneficial to enhance our understanding of the ecotoxicology and environmental behaviors of halogenated carbazoles.


Asunto(s)
Carbazoles/química , Albúmina Sérica Humana/química , Sitios de Unión , Humanos , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta
12.
Appl Environ Microbiol ; 82(22): 6748-6756, 2016 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-27613682

RESUMEN

Promiscuous enzymes are generally considered to be starting points in the evolution of offspring enzymes with more specific or even novel catalytic activities, which is the molecular basis of producing new biological functions. Mhg, a typical α/ß fold hydrolase, was previously reported to have both γ-lactamase and perhydrolase activities. However, despite having high structural similarity to and sharing an identical catalytic triad with an extensively studied esterase from Pseudomonas fluorescens, this enzyme did not show any esterase activity. Molecular docking and sequence analysis suggested a possible role for the entry of the binding pocket in blocking the entrance tunnel, preventing the ester compounds from entering into the pocket. By engineering the entrance tunnel with only one or two amino acid substitutions, we successfully obtained five esterase variants of Mhg. The variants exhibited a very broad substrate acceptance, hydrolyzing not only the classical p-nitrophenol esters but also various types of chiral esters, which are widely used as drug intermediates. Site 233 at the entrance tunnel of Mhg was found to play a pivotal role in modulating the three catalytic activities by adjusting the size and shape of the tunnel, with different amino acid substitutions at this site facilitating different activities. Remarkably, the variant with the L233G mutation was a very specific esterase without any γ-lactamase and perhydrolase activities. Considering the amino acid conservation and differentiation, this site could be a key target for future protein engineering. In addition, we demonstrate that engineering the entrance tunnel is an efficient strategy to regulate enzyme catalytic capabilities. IMPORTANCE: Promiscuous enzymes can act as starting points in the evolution of novel catalytic activities, thus providing a molecular basis for the production of new biological functions. In this study, we identified a critical amino acid residue (Leu233) at the entry of the substrate tunnel of a promiscuous enzyme, Mhg. We found that substitution of this residue with smaller amino acids such as Gly, Ala, Ser, or Pro endowed the enzyme with novel esterase activity. Different amino acids at this site can facilitate different catalytic activities. These findings exhibited universal significance in this subset of α/ß fold hydrolases, including Mhg. Furthermore, we demonstrate that engineering the entrance tunnel is an efficient strategy to evolve new enzyme catalytic capabilities. Our study has important implications for the regulation of enzyme catalytic promiscuity and development of protein engineering methodologies.


Asunto(s)
Amidas/metabolismo , Ácidos Carboxílicos/metabolismo , Esterasas/genética , Esterasas/metabolismo , Ingeniería de Proteínas/métodos , Sustitución de Aminoácidos , Sitios de Unión , Biocatálisis , Hidrolasas de Éster Carboxílico/genética , Hidrolasas de Éster Carboxílico/metabolismo , Dominio Catalítico/genética , Escherichia coli/genética , Esterasas/química , Hidrólisis , Cinética , Modelos Moleculares , Simulación del Acoplamiento Molecular , Mutagénesis Sitio-Dirigida , Nitrofenoles/metabolismo , Pseudomonas fluorescens/enzimología , Pseudomonas fluorescens/genética
13.
Brain Behav Immun ; 42: 81-8, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24929195

RESUMEN

BACKGROUND: Chronic inflammation may be involved in combat-related post-traumatic stress disorder (PTSD) and may help explain comorbid physical diseases. However, the extent to which combat exposure per se, depression, or early life trauma, all of which are associated with combat PTSD, may confound the relationship between PTSD and inflammation is unclear. METHODS: We quantified interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and C-reactive protein (CRP) in 51 combat-exposed males with PTSD and 51 combat-exposed males without PTSD, and assessed PTSD and depression severity as well as history of early life trauma. To decrease the possibility of Type I errors, we summed standardized scores of IL-1ß, IL-6, TNFα, IFNγ and CRP into a total "pro-inflammatory score". PTSD symptom severity was assessed with the Clinician Administered PTSD Scale (CAPS) rating scale. RESULTS: Subjects with PTSD had significantly higher pro-inflammatory scores compared to combat-exposed subjects without PTSD (p=0.006), and even after controlling for early life trauma, depression diagnosis and severity, body mass index, ethnicity, education, asthma/allergies, time since combat and the use of possibly confounding medications (p=0.002). Within the PTSD group, the pro-inflammatory score was not significantly correlated with depressive symptom severity, CAPS total score, or with the number of early life traumas. CONCLUSIONS: Combat-related PTSD in males is associated with higher levels of pro-inflammatory cytokines, even after accounting for depression and early life trauma. These results, from one of the largest studies of inflammatory cytokines in PTSD to date, suggest that immune activation may be a core element of PTSD pathophysiology more so than a signature of combat exposure alone.


Asunto(s)
Trastornos de Combate/sangre , Citocinas/sangre , Trastorno Depresivo/sangre , Trastornos por Estrés Postraumático/sangre , Estrés Psicológico/sangre , Adulto , Proteína C-Reactiva/metabolismo , Trastornos de Combate/complicaciones , Trastorno Depresivo/complicaciones , Humanos , Inflamación/sangre , Inflamación/complicaciones , Interleucina-1beta/sangre , Interleucina-6/sangre , Acontecimientos que Cambian la Vida , Masculino , Personal Militar , Trastornos por Estrés Postraumático/complicaciones , Estrés Psicológico/complicaciones , Factor de Necrosis Tumoral alfa/sangre , Adulto Joven
14.
Mol Pharm ; 11(10): 3279-90, 2014 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-24754897

RESUMEN

Spherical nanoparticles as a classic delivery vehicle for anticancer drugs have been extensively investigated, but study on the shape of nanoparticles has received little attention until now. Here, a nonspherical poly(ethylene glycol) (PEG)-stabilized bilayer nanodisk consisting of 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC) and PEG5000-glyceryl distearate (PEG5K-GCDS) was prepared for doxorubicin delivery, called DOX-Disks. The prepared disks were open bilayer structures, with a hydrophobic discoid center built by DSPC and a hydrophilic PEG edge. Mean particle diameter of the disk was 80.14 nm, and the disk height was about 6 nm with aspect ratio about 12. Encapsulation efficiency of DOX-Disks was as high as 96.1%, and DOX release from DOX-Disks was pH-dependent (25.6% of total DOX released at 24 h in pH 7.4). The pharmacokinetic performances showed that DOX-Disks demonstrated long circulation time in blood and larger AUC (11.7-fold of t1/2 and 31.7-fold of AUC) in rats compared with DOX solutions (DOX-Sol). Tissue distribution in H22 tumor bearing mice demonstrated higher tumor accumulation (9.7-fold) and lower heart toxicities (25.7-fold) at 48 h after iv administration, in comparison with DOX-Sol. In addition, DOX-Disks exhibited much effectiveness in inhibiting tumor cell growth, and the IC50 values were 2.03, 0.85, and 0.86 µg/mL for DOX-Sol and 0.23, 0.24, and 0.20 µg/mL for DOX-Disks after treatment for 48, 72, and 96 h against MCF-7/Adr cells, respectively. DOX-Disks were taken up into MCF-7/Adr cells via energy-dependent endocytosis processes, involved in clathrin-mediated, macropinocytosis-mediated, and non-clathrin- and non-caveolae-mediated endocytosis pathways. In summary, such PEG-stabilized bilayer nanodisks could be one of the promising carriers for antitumor drugs via extended blood circulation and improved tumor distribution.


Asunto(s)
Antineoplásicos/química , Doxorrubicina/química , Nanopartículas/química , Polietilenglicoles/química , Animales , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Humanos , Masculino , Ratones , Microscopía Electrónica de Transmisión , Nanopartículas/ultraestructura , Ratas , Ratas Wistar
15.
Nutr Metab (Lond) ; 21(1): 28, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796446

RESUMEN

Metabolic syndrome (MetS) is a cluster of clinical syndromes that is closely associated with an elevated risk of developing atherosclerotic cardiovascular disease. In a series of animal experiments and clinical trials, crocus sativus and its component crocin have demonstrated promising hypoglycemic effects. However, there is currently insufficient evidence regarding their impact on cardiometabolic parameters. Our study aimed to assess the impact of Crocus sativus and crocin on glycemic control in individuals with metabolic syndrome and associated disorders, as well as their potential effects on improving cardiometabolic parameters. We searched Cochrane Library, PubMed, Embase, and Web of Science databases to ascertain the pertinent randomized controlled trials (RCTs) until December 30, 2023. Q-test and I2 statistics were utilized to evaluate heterogeneity among the included studies. Data were merged using a random-effects model and presented as (WMD) with a 95% confidence interval (CI). The current comprehensive review and meta-analysis, encompassing 13 RCTs involving a total of 840 patients diagnosed with metabolic syndrome and associated disorders, demonstrates that Crocus sativus was superior to placebo on Hemoglobin A1c(HbA1c) (WMD: -0.31;95% CI [-0.44,-0.19]. P = 0.002) and systolic blood pressure(SBP) (WMD:-7.49;95% CI [-11.67,-3.30]. P = 0.99) respectively. Moreover, Crocus sativus improved fasting blood glucose (FBG) (WMD:-7.25;95% CI [-11.82, -2.57]. P = 0.002) when used crocin and on other chronic diseases. Crocus sativus reduced the total cholesterol (TC) among the metabolic syndromepatients (WMD:-13.64;95%CI [-26.26, -1.03]. P = 0.03). We demonstrated that Crocus sativus exerts beneficial effects on glycemic control and cardiometabolic parameters in individuals with metabolic syndrome and related disorders.

16.
Phytomedicine ; 130: 155753, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38795693

RESUMEN

BACKGROUND: Meningeal lymphatic vessels (mLVs) have great potential to be the therapeutic target for ß Amyloid protein (Aß) clearing in Alzheimer's disease (AD), but the regulatory methods of the mLVs are limited. The lymphatic valve, marked by FOXC2, is the fundamental structure for maintaining stable lymphatic drainage function. Preliminary evidence suggested that borneol (BO) as the classical phytochemicals could enhance the expression of FOXC2 in the mLVs of healthy mice. PURPOSE: This study aims to explore the regulatory ability of BO on lymphatic valves of mLVs in the AD model mice. STUDY DESIGN: We used the intracerebroventricular injection of Aß42 oligomers to construct the AD-like symptoms model induced by toxic protein deposition. We administered BO nano micelles(BO-Ms) orally before and after to simulate the AD prevention and treatment strategy. METHODS: Herein, this study characterized the efficacy and pathways of BO-Ms for regulating mLVs in AD model by Rt-PCR, WB and confocal microscopy, and determined the effects of BO-Ms on Aß clearance, behavior and safety of AD mice. RESULTS: The AD modeling process severely impaired the expression of lymphatic valves. However, after oral administering BO-Ms for prevention and treatment, an increase in the lymphatic valves of the transverse sinus was observed, which derived from the up-regulation of the transcription factor (FOXC2 and Akt) and the down-regulation of the transcription inhibitors (FOXO1 and PRDM1). Furthermore, the effects of BO-Ms on the lymphatic valves could enhance the lymphatic drainage of the mLVs in AD-like mice, promoting the clearance of toxicity aggregates, protecting neurons, and alleviating AD-like symptoms. Simultaneously, continuous oral BO-Ms for 30 days didn't show any significant organ toxicity. The most important thing was that the preventive effect of BO administration was superior to therapeutic administration in all data. CONCLUSION: In summary, our research indicated that BO is a promoter of lymphatic valve formation in the mLVs, and could prevent or repair damage caused by toxic Aß42. BO was the only bioactive natural product with the ability to regulate mLVs valves. Thus, BO has the potential to become phytochemicals for alleviating AD symptoms by enhancing the drainage function of mLVs.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Canfanos , Modelos Animales de Enfermedad , Factores de Transcripción Forkhead , Animales , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/prevención & control , Enfermedad de Alzheimer/tratamiento farmacológico , Ratones , Canfanos/farmacología , Factores de Transcripción Forkhead/metabolismo , Masculino , Vasos Linfáticos/efectos de los fármacos , Meninges/efectos de los fármacos , Ratones Endogámicos C57BL
17.
Curr Med Imaging ; 20: 1-8, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38389370

RESUMEN

BACKGROUND: Pulmonary embolism (PE) is a relatively rare vascular complication of acute pancreatitis (AP), and its mortality rate is high. To our knowledge, relevant literature reports still need to be summarized. In this study, we analyzed the clinical characteristics, treatment, and prognosis of five patients with AP complicated by PE and summarized and reviewed the relevant literature. METHODS: Clinical data of patients with AP complicated by PE treated in Taizhou Hospital of Zhejiang Province between January 2017 and September 2022 were retrospectively collected. Combined with the relevant literature, the clinical characteristics, treatment, and prognoses of patients with AP combined with PE were analyzed and summarized. RESULTS: Five patients were eventually enrolled in this study. Among the five patients with AP complicated by PE, all (100%) had symptoms of malaise, primarily chest tightness, shortness of breath, and dyspnea. All patients (100%) had varied degrees of elevated D-dimer levels and a significant decrease in the pressure of partial oxygen (PO2) and pressure of arterial oxygen to fractional inspired oxygen concentration ratio (PaO2/FiO2). Computed tomographic angiography (CTA) or pulmonary ventilation/perfusion imaging revealed a pulmonary artery filling defect in these patients. One patient (20%) had left calf muscular venous thrombosis before the occurrence of PE. Four patients (80%) were treated with lowmolecular- weight heparin (LMWH), and one patient (20%) was treated with rivaroxaban during hospitalization; all continued oral anticoagulant therapy after discharge. All patients (100%) were cured and discharged. No patients showed recurrence of AP or PE. CONCLUSION: PE is a rare but life-threatening complication of AP. However, once diagnosed, early treatment with anticoagulation or radiological interventional procedures is effective, and the prognosis is good. Core Tips: Pulmonary embolism (PE) is a rare but life-threatening complication of acute pancreatitis (AP). Its early diagnosis and timely anticoagulation or radiological intervention can reduce mortality. However, only nine cases have been reported in the English literature thus far, and they are all case reports. Our study is the first systematic analysis of patients with AP combined with PE with a review of the relevant literature. Our patients and those reported in the literature were discharged with good prognoses under treatment such as anticoagulation and vascular intervention. These cases remind clinicians that, in patients with AP, especially those with risk factors for venous thrombosis, it is necessary to monitor the D-dimer level dynamically. Clinicians should pay attention to AP patients' symptoms and related examinations to reduce the chance of a missed diagnosis or misdiagnosis of PE.


Asunto(s)
Pancreatitis , Embolia Pulmonar , Trombosis de la Vena , Humanos , Enfermedad Aguda , Anticoagulantes/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Oxígeno , Pancreatitis/complicaciones , Pancreatitis/diagnóstico por imagen , Pancreatitis/tratamiento farmacológico , Pronóstico , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Trombosis de la Vena/complicaciones , Trombosis de la Vena/tratamiento farmacológico
18.
Plant Commun ; 5(6): 100921, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38616491

RESUMEN

CRISPR-Cas-based genome editing holds immense promise for advancing plant genomics and crop enhancement. However, the challenge of low editing activity complicates the identification of editing events. In this study, we introduce multiple single transcript unit surrogate reporter (STU-SR) systems to enhance the selection of genome-edited plants. These systems use the same single guide RNAs designed for endogenous genes to edit reporter genes, establishing a direct link between reporter gene editing activity and that of endogenous genes. Various strategies are used to restore functional reporter genes after genome editing, including efficient single-strand annealing (SSA) for homologous recombination in STU-SR-SSA systems. STU-SR-base editor systems leverage base editing to reinstate the start codon, enriching C-to-T and A-to-G base editing events. Our results showcase the effectiveness of these STU-SR systems in enhancing genome editing events in the monocot rice, encompassing Cas9 nuclease-based targeted mutagenesis, cytosine base editing, and adenine base editing. The systems exhibit compatibility with Cas9 variants, such as the PAM-less SpRY, and are shown to boost genome editing in Brassica oleracea, a dicot vegetable crop. In summary, we have developed highly efficient and versatile STU-SR systems for enrichment of genome-edited plants.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Genoma de Planta , Oryza , Edición Génica/métodos , Oryza/genética , Genes Reporteros , ARN Guía de Sistemas CRISPR-Cas/genética
19.
J Phys Chem Lett ; 14(25): 5867-5875, 2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37341497

RESUMEN

Focusing on LaFeO3, we investigated the effects of magnetic ordering on carrier relaxation using time-domain density functional theory and nonadiabatic molecular dynamics. The results show that the hot energy and carrier relaxation occur on a sub-2 ps time scale due to the strong intraband nonadiabatic coupling, and the corresponding time scales are distinct depending on the magnetic ordering of LaFeO3. Importantly, the energy relaxation is slower than hot carrier relaxation, guaranteeing photogenerated hot carriers can be effectively relaxed to the band edge before cooling. Following hot carrier relaxation, the charge recombination occurs on the nanosecond scale due to the small interband nonadiabatic coupling and short pure-dephasing times. In addition, the A-AFM system has the longest carrier lifetimes because of its weakest nonadiabatic coupling. Our study suggests that the carrier lifetime can be controlled by changing the magnetic ordering of perovskite oxides and provides valuable principles for the design of high-performance photoelectrodes.

20.
ISA Trans ; 141: 132-142, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37121822

RESUMEN

As an essential research task in artificial intelligence (AI), the estimation of 3D human poses has important application value in virtual reality, medical diagnosis, athlete training and other fields. However, human pose recovery and retargeting require the acquisition of detailed visual data containing private information, which has led to increasing concerns about user privacy and security. Therefore, we build a lightweight framework, called Human Motion Parameters Prediction (HMPP), which can infer the 3D mesh and 3D skeletal joint points of the human body while protecting the privacy of the user. The proposed method successfully reduces or suppresses privacy attributes while ensuring important features to perform human pose estimation. The 2D and 3D joints are used for supervision to improve the interpretability of the model at each stage. In addition, the prediction of the camera's internal parameters is added so that the model can be augmented with projection supervision, thereby using more 2D datasets for training and improving the generalization ability of the model. Finally, the predicted motion parameters are used for 3D reconstruction and motion retargeting. Experiments show that our approach can achieve excellent evaluation results on multiple datasets and avoid inadvertently compromising private and sensitive data.


Asunto(s)
Inteligencia Artificial , Privacidad , Humanos , Movimiento (Física)
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