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1.
Neural Regen Res ; 20(1): 139-158, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38767483

RESUMEN

Parkinson's disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such as α-synuclein in neurons. As one of the major intracellular degradation pathways, the autophagy-lysosome pathway plays an important role in eliminating these proteins. Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance of α-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson's disease. Moreover, multiple genes associated with the pathogenesis of Parkinson's disease are intimately linked to alterations in the autophagy-lysosome pathway. Thus, this pathway appears to be a promising therapeutic target for treatment of Parkinson's disease. In this review, we briefly introduce the machinery of autophagy. Then, we provide a description of the effects of Parkinson's disease-related genes on the autophagy-lysosome pathway. Finally, we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy-lysosome pathway and their applications in Parkinson's disease.

2.
Int J Biol Macromol ; 279(Pt 4): 135520, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39260643

RESUMEN

Fluoride ion pollution in water has become a serious threat to the water environment and human health. Adsorption is a promising means of fluoride removal, but it also faces challenges such as the difficult separation and recovery of powdered particles, the leaching of modified coatings from adsorbents, and the structural disintegration of macroscopic adsorbents. For addressing the above challenges, glutaraldehyde/polyvinyl alcohol co-crosslinked ZrSAF/chitosan spongy composites (ZrS/GPCS) were prepared by utilizing encapsulation strategies and cross-linking. ZrS/GPCS-1, ZrS/GPCS-3 and ZrS/GPCS-4 were prepared due to the different amounts of cross-linking agents. The results showed that their fluoride ion adsorption capacities were 42.02, 44.44 and 39.84 mg/g, respectively. The removal of fluoride ions by ZrS/GPCS was maintained at >80 % in the pH range of 4-10. The addition of glutaraldehyde and polyvinyl alcohol affected the contact efficiency of fluoride ions with chitosan and ZrSAF, influencing the adsorption rate and adsorption effect. Glutaraldehyde, polyvinyl alcohol and ZrSAF improved the thermal stability, mechanical properties and structural integrity of chitosan matrix. Both the chitosan matrix and the internal ZrSAF played an important role in fluoride removal, and the removal mechanisms included electrostatic interaction, hydrogen bonding, and complexation.

3.
Cancer Control ; 31: 10732748241270583, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39152700

RESUMEN

OBJECTIVE: The aim of this study was to analyze the clinical significance and prognostic value of CD8+ T cell-related regulatory genes in hepatocellular carcinoma (HCC). METHODS: This was a retrospective study. We combined TCGA-LIHC and single-cell RNA sequencing data for Lasso-Cox regression analysis to screen for CD8+ T cell-associated genes to construct a novel signature. The expression of the signature genes was detected at cellular and tissue levels using qRT-PCR, immunohistochemistry, and tissue microarrays. The CIBERSORT algorithm was then used to assess the immune microenvironmental differences between the different risk groups and a drug sensitivity analysis was performed to screen for potential HCC therapeutic agents. RESULTS: An 8-gene CD8 + T cell-associated signature (FABP5, GZMH, ANXA2, KLRB1, CD7, IL7R, BATF, and RGS2) was constructed. Survival analysis showed that high-risk patients had a poorer prognosis in all cohorts. Tumor immune microenvironment analysis revealed 22 immune cell types that differed significantly between patients in different risk groups, with patients in the low-risk group having an immune system that was more active in terms of immune function. Patients in the high-risk group were more prone to immune escape and had a poorer response to immunotherapy, and AZD7762 was screened as the most sensitive drug in the high-risk group. Finally, preliminary experiments have shown that BATF has a promoting effect on the proliferation, migration and invasion of HuH-7 cells. CONCLUSIONS: The CD8+ T-cell-associated signature is expected to be a tool for optimizing individual patient decision-making and monitoring protocols, and to provide new ideas for treatment and prognostic assessment of HCC.


Asunto(s)
Linfocitos T CD8-positivos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Pronóstico , Microambiente Tumoral/inmunología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica
4.
Int J Biol Macromol ; 277(Pt 4): 134539, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39122065

RESUMEN

Cellulases have been widely used in many fields such as animal feed, textile, food, lignocellulose bioconversion, etc. Efficient and low-cost production of cellulases is very important for its industrial application, especially in bioconversion of lignocellulosic biomass. Filamentous fungi are currently widely used in industrial cellulase production due to their ability to secrete large amounts of active free cellulases extracellularly. This review comprehensively summarized the research progress on cellulases from filamentous fungi in recent years, including filamentous fungi used for cellulase production and its modification strategies, enzyme compositions, characterization methods and application of fungal cellulase systems, and the production of fungal cellulase includes production processes, factors affecting cellulase production such as inducers, fermentation medium, process parameters and their control strategies. Also, the future perspectives and research topics in fungal cellulase production are presented in the end of the review. The review helps to deepen the understanding of the current status of fungal cellulases, thereby promoting the production technology progress and industrial application of filamentous fungal cellulase.


Asunto(s)
Celulasa , Fermentación , Hongos , Celulasa/biosíntesis , Celulasa/metabolismo , Hongos/enzimología , Celulasas/metabolismo , Celulasas/biosíntesis , Biomasa , Lignina
5.
Heliyon ; 10(14): e34182, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39108862

RESUMEN

Orexins are a family of neuropeptides secreted by neurons in the lateral hypothalamus (LH). These peptides act widespreadly across the body by interacting with specific orexin receptors on target cells, which comprise the orexinergic system. Emerging evidence has revealed that the orexinergic system is tightly associated with neuropsychiatric disorders; however, the underlying mechanisms require further exploration. Neuropsychiatric disorders have also been associated with neuroplasticity, while orexins have been shown to play regulatory roles in neuronal plasticity. As such, this review aims to summarize the recent progress of research investigating the roles of the orexinergic system in neuronal plasticity and associated neuropsychiatric disorders, including addiction, depression, and schizophrenia, which may provide novel insights into the mechanism of the orexinergic system in the pathogenesis of these neuropsychiatric disorders.

6.
Discov Oncol ; 15(1): 353, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150637

RESUMEN

BACKGROUND: M2-like tumor-associated macrophages (M2-like TAMs) play key roles in tumor progression and the immune response. However, the clinical significance and prognostic value of M2-like TAMs-associated regulatory genes in gastric cancer (GC) have not been clarified. METHODS: Herein, we identified M2-like TAM-related genes by weighted gene coexpression network analysis of TCGA-STAD and GSE84437 cohort. Lasso-Cox regression analyses were then performed to screen for signature genes, and a novel signature was constructed to quantify the risk score for each patient. Tumor mutation burden (TMB), survival outcomes, immune cells, and immune function were analyzed in the risk groups to further reveal the immune status of GC patients. A gene-drug correlation analysis and sensitivity analysis of anticancer drugs were used to identify potential therapeutic agents. Finally, we verified the mRNA expression of signature genes in patient tissues by qRT-PCR, and analyzed the expression distribution of these genes by IHC. RESULTS: A 4-gene (SERPINE1, MATN3, CD36, and CNTN1) signature was developed and validated, and the risk score was shown to be an independent prognostic factor for GC patients. Further analyses revealed that GC patients in the high-risk group had a worse prognosis than those in the low-risk group, with significant differences in TMB, clinical features, enriched pathways, TIDE score, and tumor microenvironment features. Finally, we used qRT-PCR and IHC analysis to verify mRNA and protein level expression of signature genes. CONCLUSION: These findings highlight the importance of M2-like TAMs, provide a new perspective on individualized immunotherapy for GC patients.

7.
Chaos ; 34(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38980384

RESUMEN

In this work, we investigate how the seasonal variation in the number of individuals who are tested for an HIV antibody in outpatient clinics affects the HIV transmission patterns in China, which has not been well studied. Based on the characteristics of outpatient testing data and reported cases, we establish a periodic infectious disease model to study the impact of seasonal testing on HIV transmission. The results indicate that the seasonal testing is a driving factor for the seasonality of new cases. We demonstrate the feasibility of ending the HIV/AIDS epidemic. We find that the diagnostic rates related to testing play a crucial role in controlling the size of the epidemic. Specifically, when considering minimizing both infected individuals and diagnostic rates, the level of attention paid to undiagnosed infected individuals is always positively correlated with the optimal diagnostic rates, while the optimal diagnostic rates are negatively correlated with the size of the epidemic at the terminal time.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Epidemias , Infecciones por VIH , Estaciones del Año , Humanos , China/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/prevención & control
8.
Phytother Res ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39038923

RESUMEN

Tubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high-glucose-stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta-hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl-transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high-glucose-induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress-associated proximal tubular injury by upregulating CPT1A-mediated K99 succinylation of HSD17B10 to maintain RNase P activity.

9.
Infect Dis Model ; 9(3): 975-994, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38881537

RESUMEN

Parameter identification involves the estimation of undisclosed parameters within a system based on observed data and mathematical models. In this investigation, we employ DAISY to meticulously examine the structural identifiability of parameters of a within-host SARS-CoV-2 epidemic model, taking into account an array of observable datasets. Furthermore, Monte Carlo simulations are performed to offer a comprehensive practical analysis of model parameters. Lastly, sensitivity analysis is employed to ascertain that decreasing the replication rate of the SARS-CoV-2 virus and curbing the infectious period are the most efficacious measures in alleviating the dissemination of COVID-19 amongst hosts.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38865227

RESUMEN

This article focuses on investigating the stability issue for recurrent neural networks (RNNs) with interval time-varying delays (TVDs) based on a flexible delay-dividing method with parameters, which are related to the delay derivative. First, an interval of delay is separated into parametric subintervals via the linear combination technique. Then, an establishment of Lyapunov-Krasovskii functional (LKF) is connected to the parameters, and a novel linear technology is suggested to dispose of integral terms in the derivatives of the constructed function. Finally, the validity and advantage of the inferred criteria are interpreted by the comparison of representative simulation examples.

11.
Mol Biol Rep ; 51(1): 669, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787465

RESUMEN

BACKGROUND: The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) is a major pathological hallmark of Parkinson's disease (PD). Orexin B (OXB) has been reported to promote the growth of DA neurons. However, the roles of OXB in the degeneration of DA neurons still remained not fully clear. METHODS: An in vivo PD model was constructed by administrating 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Pole test was performed to investigate the motor function of mice and the number of DA neurons was detected by immunofluorescence (IF). A PD cell model was established by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+). OXB was added to the culture medium 2 h after MPP + treatment. Microscopic analysis was carried out to investigate the function of OXB in the cell model of PD 24 h after MPP + challenge. RNA-Seq analysis of the PD cell model was performed to explore the possible mechanisms. Western blot was used to detect the phosphorylation levels of extracellular signal-regulated kinase (ERK). RESULTS: OXB significantly decreased the DA neurons death caused by MPTP, alleviated MPP+-induced neurotoxicity in SH-SY5Y cells, and robustly enhanced the weight and motor ability of PD mice. Besides, RNA-Seq analysis demonstrated that the mitogen-activated protein kinase (MAPK) pathway was involved in the pathology of PD. Furthermore, MPP + led to increased levels of phosphorylation of ERK (p-ERK), OXB treatment significantly decreased the levels of p-ERK in MPP+-treated SH-SY5Y cells. CONCLUSIONS: This study demonstrated that OXB exerts a neuroprotective role associated with reduced ERK phosphorylation in the PD model. This suggests that OXB may have therapeutic potential for treatment of PD.


Asunto(s)
1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Neuronas Dopaminérgicas , Quinasas MAP Reguladas por Señal Extracelular , Orexinas , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Animales , Ratones , Fosforilación/efectos de los fármacos , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Orexinas/metabolismo , Orexinas/farmacología , Humanos , Masculino , Línea Celular Tumoral , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Ratones Endogámicos C57BL , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , 1-Metil-4-fenilpiridinio/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos
12.
Neoplasma ; 71(1): 1-12, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38295103

RESUMEN

Semaphorins are originally described as regulators of nervous system development. Besides, members of the semaphorin family play important roles in the growth, metastasis, and angiogenesis of solid tumors. In contrast to the other semaphorin subclasses, semaphorin class 4 has both membrane-bound and active soluble forms. Soluble class 4 semaphorins in body fluids (blood and saliva) may serve as potential biomarkers for early diagnosis and prognosis prediction of specific cancers. The class 4 semaphorins also transduce signal in cancer cells in a cell membrane-bound form, thereby regulating cancer progression. In solid tumors, class 4 semaphorins can act as ligands in active soluble forms, regulating cancer progression via autocrine and paracrine to activate signal transduction in cancer cells or endothelial cells in the tumor microenvironment. Targeting class 4 semaphorins may be a novel strategy for specific cancer therapy. However, the expression of class 4 semaphorins in solid tumors and the responsive pathogenesis are still controversial. Therefore, this review summarizes the specific expression regulation of class 4 semaphorin members in different types of solid tumors and the mechanisms involved in cancer progression.


Asunto(s)
Neoplasias , Semaforinas , Humanos , Neovascularización Patológica/patología , Semaforinas/genética , Células Endoteliales , Neoplasias/metabolismo , Transducción de Señal/fisiología , Microambiente Tumoral
13.
Int J Biol Macromol ; 264(Pt 1): 129762, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38281535

RESUMEN

Lignin, as an amorphous three-dimensional aromatic polymer, was able to self-assemble into lignin nanoparticles (LNPs) to realize valorization of lignin. Here, lignin-xylan extractives were extracted from grape seed (GS) and poplar by acidic THF at room temperature, and effectively produced lignin-xylan nanospheres via spin evaporation. The morphology and chemical properties of nanospheres were determined by its natural origins, consequently influencing its application. For the lignin-xylan extractive from grape seed, the lignin was composed of guaiacyl (G) and p-hydroxylphenyl (H) units and the hollowed nanospheres (GS-LNPs) with 362.72 nm diameter was produced. The extractive from poplar was composed of G-syringyl (S) typed lignin (80.30 %) and xylan (12.33 %), that can assemble into LNPs with smaller size (229.87 nm), better PDI (0.1), and light color. The hybrid particles showed the qualities of lignin and xylan, that properties led to the LNPs@PVA composite films with UV-blocking capability, strong mechanical strength and hydrophobicity, and transparency ability of visible light. P-LNPs showed better performance as the film additives, due to its lower particles size and high content of unconjugated -OH from xylan. Xylan was significant in the composite films, and lowering the xylan content resulted in the decrease of the composite film's mechanical properties and hydrophobicity.


Asunto(s)
Lignina , Nanosferas , Lignina/química , Xilanos/química , Polímeros
14.
Bioresour Technol ; 394: 130242, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38145760

RESUMEN

Brewer's spent grain (BSG) is a major low-value by-product of beer industry. To realize the high value application of BSG, this work proposed a strategy to produce single cell protein (SCP) with oligosaccharide prebiotics from BSG, via ammoniation pretreatment, enzymatic hydrolysis, and fermentation. The optimum conditions of ammoniation pretreatment obtained by response surface method were 11 % ammonia dosage (w/w), 63 °C for 26 h. Suitable enzyme and yeast were screened to enhance the conversion of cellulose and hemicellulose in BSG into sugars and maximize the SCP yield. It was shown that using lignocellulolytic enzyme SP from Penicillium oxalicum and Trichosporon cutaneum, about 310 g of SCP with 80 g of arabinoxylo-oligosaccharides were obtained from 1000 g of BSG. This process is low cost, high efficiency, and easy to implement, which has good industrial application prospects.


Asunto(s)
Celulosa , Proteínas en la Dieta , Grano Comestible , Fermentación , Grano Comestible/metabolismo , Celulosa/metabolismo , Saccharomyces cerevisiae/metabolismo
15.
J Theor Biol ; 575: 111635, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37858903

RESUMEN

To estimate the risk of human immunodeficiency virus (HIV) infection through sexual transmission in China from 2013 to 2017 accurately, we divide the total population into three groups, namely, men who have sex with men (MSM) group; non-marital and commercial sex group: female sex workers (FSW) and their clients (FSWC); non-marital and non-commercial sex group: general women (GW) and general men (GM). First, the risks of HIV infection among men who have contacts with infected men or infected women decrease annually. Second, the number of contacts between susceptible FSWC and infected FSW per unit time is greater than that between susceptible MSM and infected MSM, and also greater than that between susceptible FSW and infected FSWC, which suggests that the intervention for commercial sex of heterosexual men should be strengthened. Third, the effective reproduction numbers of the MSM group and non-commercial sex group decrease annually, while the effective reproduction number of the commercial sex group decreases first, then increases, because the risk of women being infected by men decreases first, then increases. Additionally, the effective reproduction number of the commercial sex group exceeds that of the MSM group after 2015, which indicates that commercial sex contributes more and more to the HIV/AIDS epidemic.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Trabajadores Sexuales , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Trabajo Sexual , Síndrome de Inmunodeficiencia Adquirida/epidemiología , China/epidemiología , Medición de Riesgo , Conducta Sexual
16.
Int J Biol Macromol ; 253(Pt 2): 126796, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37689294

RESUMEN

Diabetic patients often experience long-term risks due to chronic inflammation and delayed re-epithelialization during impaired wound healing. Although the severity of this condition is well known, the treatment options for diabetic wounds are limited. Rhubarb charcoal, a well-known traditional Chinese medicine, has been used to treat skin wounds for thousands of years. We produced a chitosan/silk fibroin sponge scaffold loaded with natural carbonized rhubarb and crosslinked it by freeze-drying to create a highly efficient RCS/SF scaffold. Rhubarb carbon and carboxymethyl chitosan exhibit antibacterial activity and promote wound healing. Owing to its 3D porous structure, this scaffold is antibacterial and pro-angiogenic. It also possesses remarkable properties, such as excellent swelling and biocompatibility. The supportive effect of carbonized rhubarb on mouse fibroblast migration is mediated at the cellular/tissue level by increased skin neovascularization and re-epithelization. Compared to the control group, RCS/SF scaffolds promoted faster healing, increased neovascularization, enhanced collagen deposition, and re-epithelialization within two weeks. The scaffold's pro-healing properties and efficient release of carbonized rhubarb, with rapid hemostatic and good sterilization effects, make it an outstanding candidate for treating diabetic wounds and novel therapeutic interventions for diabetic ulcers.


Asunto(s)
Quitosano , Diabetes Mellitus , Fibroínas , Rheum , Humanos , Ratones , Animales , Fibroínas/farmacología , Carbón Orgánico , Quitosano/química , Cicatrización de Heridas , Diabetes Mellitus/tratamiento farmacológico , Inflamación , Hemostasis , Antibacterianos/farmacología
17.
Zhen Ci Yan Jiu ; 48(8): 764-72, 2023 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-37614134

RESUMEN

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) in promoting the browning of white adipose tissue in middle-aged and aged obese rats induced by high fat by regulating AMP-activated protein kinase (AMPK) /silence-information regulatory factor 1 (Sirt1) pathway and neuregulin 4 (Nrg4). METHODS: Twenty-four male SD rats were randomized into blank control, model and EA groups (n=8 per group). The obesity model was established by feeding the rats with high-fat diet for 6 weeks. For the EA group, EA (2 Hz/15 Hz, 1.5 mA) was applied to "Guanyuan" (CV4) and bilateral "Shenshu" (BL23), "Fenglong" (ST40) and "Tianshu" (ST25) for 20 min, once a day, 5 days a week for 6 weeks. Rats of the blank control and model groups were also restrained for 20 min. The body mass and food intake were measured every week, and the Lee's index, epididymal fat, perirenal fat and brown adipose tissue were weighed. The contents of serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and norepinephrine (NE) were determined by ELISA. H.E. staining was used to observe the morphological changes of white and brown adipose tissue. The mRNA expression levels of mitochondrial uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α), PR-domain protein 16 (PRDM16), peroxisome proliferator activated receptor γ (PPARγ) and Nrg4 in the adipose tissue were detected by quantitative real time PCR, and the protein expression levels of Nrg4, AMPKα, Sirt1 and interleukin-6 (IL-6) in the white and brown adipose tissue were detected by Western blot. RESULTS: Compared with the blank control group, the body mass, food intake, the Lee's index, epididymal fat and perirenal fat mass, and serum TG, TC and LDL-C contents and the expression level of IL-6 protein were significantly increased (P<0.01, P<0.05, P<0.001), and the brown adipose mass, serum HDL-C and NE contents, the expression levels of UCP1, PGC-1α, PRDM16, PPARγ and Nrg4 mRNAs, and the protein expression levels of AMPKα, Sirt1 and Nrg4 proteins in both white and brown adipose tissues were significantly decreased in the model group (P<0.01, P<0.05). After EA intervention, the increased levels of body mass, food intake, Lee's index, epididymal fat and perirenal fat mass, serum TG, TC and LDL-C contents, and the expression of IL-6 protein, and the decreased levels of brown adipose mass, serum HDL-C and NE contents, expression levels of UCP1, PGC-1α, PRDM16, PPARγ and Nrg4 mRNAs, and those of AMPKα, Sirt1 and Nrg4 proteins in both white and brown adipose tissues were apparently reversed(P<0.05, P<0.01, P<0.001). H.E. staining showed an increase of the volume and content of intracellular vacuoles of both white and brown adipose tissues, disordered arrangement of cells with vague boundary in the model group, which was relatively milder including a decrease of volume and content of vacuoles of both white and brown adipose, neat arrangement of cells with clear boundary. CONCLUSION: EA intervention can improve lipid metabolism and promote white adipose tissue browning in middle-aged and aged obese rats, which is possibly associated with its functions in activating AMPK/Sirt1 signaling pathway and up-regulating the level of Nrg4.


Asunto(s)
Electroacupuntura , Metabolismo de los Lípidos , Animales , Masculino , Ratas , Tejido Adiposo Pardo , Tejido Adiposo Blanco , Proteínas Quinasas Activadas por AMP/genética , LDL-Colesterol , Interleucina-6 , Metabolismo de los Lípidos/genética , Obesidad/genética , Obesidad/terapia , PPAR gamma , Ratas Sprague-Dawley , Sirtuina 1/genética
19.
Int J Mol Sci ; 24(13)2023 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-37445866

RESUMEN

Endoglucanase (EG) is a key enzyme during enzymatic preparation of cellulose nanocrystals (CNCs). Myceliophthora thermophila is a thermophilic fungus that has thermal properties and a high secretion of endoglucanases (EGs), and could serve as potential sources of EGs for the preparation of CNCs. In this work, four different GH families (GH5, GH7, GH12, and GH45) of EGs from M. thermophila were expressed and purified, and their enzymatic characteristics and feasibility of application in CNC preparation were investigated. It was shown that the MtEG5A from M. thermophila has good potential in the enzymatic preparation of CNCs using eucalyptus dissolving pulp as feedstock. It was also observed that there was a synergistic effect between the MtEG5A and other MtEGs in the preparation of CNCs, which improved the yield and properties of CNCs obtained by enzymatic hydrolysis. This study provides a reference for understanding the enzymatic characteristics of different families of EGs from M. thermophile and their potential application in nanocellulose production.


Asunto(s)
Celulasa , Eucalyptus , Nanopartículas , Celulasa/química , Celulosa/química , Eucalyptus/química , Nanopartículas/química
20.
Eur J Pharmacol ; 953: 175825, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37269973

RESUMEN

Polycystic ovary syndrome (PCOS) is characterized by reproductive, endocrine, and metabolic disorders. Icariin has been shown to regulate endocrine and metabolic imbalances. This study aimed to determine the therapeutic effect and pharmacological mechanism of icariin in PCOS rats. Rats were fed a high-fat diet and gavaged with letrozole to induce PCOS. Thirty-six female rats were randomly divided into four groups: control, model, low-dose, and high-dose icariin. After 30 days of treatment, we evaluated the therapeutic effects on weight and diet, sex hormone levels, ovarian morphology, estrous cycle, inflammatory factors, and indicators of glucolipid metabolism. Combined with the ovarian transcriptome, we verified the key markers of apoptosis and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway by RT-qPCR for mRNA level, western blot, and immunohistochemistry for protein expression. Icariin significantly improved ovarian function and reproductive endocrine disorders by regulating sex hormones, restoring the estrous cycle, and reducing ovarian morphological damage in PCOS rats. Icariin-treated rats had lower weight gain and reduced triglycerides, fasting insulin, HOMA-IR, TNF-α, and interleukin-6 with higher high-density lipoprotein cholesterol levels than PCOS rats. TUNEL staining showed icariin improved apoptosis in the ovaries. This was supported by an increase in Bcl2 and a decrease in Bad and Bax. Icariin decreased the ratios of p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3, and p-STAT5a/STAT5a, decreased IL-6, gp130 expression, and increased cytokine-inducible SH2-containing protein (CISH) and suppressor of cytokine signaling 1 (SOCS1) expression. The pharmacological mechanism may be related to the reduction in ovarian apoptosis and inhibition of the IL-6/gp130/JAK2/STATs pathway.


Asunto(s)
Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Humanos , Ratas , Femenino , Animales , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Letrozol/efectos adversos , Interleucina-6/efectos adversos , Dieta Alta en Grasa/efectos adversos , Receptor gp130 de Citocinas/uso terapéutico , Hormonas Esteroides Gonadales
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