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1.
World J Clin Cases ; 11(1): 210-217, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36687193

RESUMO

BACKGROUND: Ochronosis, also known as alkaptonuria, is a rare autosomal recessive self-metabolic disease arising from deficiency of homogentisate 1,2 dioxygenase enzyme. It affects several organs and muscoskeletal structures. We herein report a case of a patient who presented with severe hip arthropathy complicated with late stage ochronosis. CASE SUMMARY: A 56-year-old male patient was admitted in our department in 2019 with complaints of chronic low backache and left hip pain. After the required investigations were done, lumbar disc herniation and severe hip arthritis were the initial diagnosis. A total left hip arthroplasty was performed. Ochronotic osteoarthritis was only obtained post-surgery as confirmatory diagnosis. He was again admitted mid 2022 with the same complaints on the right hip. Subsequently, he underwent a total right hip arthroplasty. Post-operative recovery and follow-ups were deemed very satisfactory. CONCLUSION: Ochronosis is an unusual diagnosis for a patient who presents with typical hip arthritis. Thus, unless meticulous history taking and advanced laboratory tests, the diagnosis can easily be missed by surgeons.

2.
Sci Rep ; 13(1): 958, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653468

RESUMO

Hypertrophic cardiomyopathy (HCM) is a genetic heart disease that is associated with many pathological features, such as a reduction in global longitudinal strain (GLS), myofiber disarray and hypertrophy. The effects of these features on left ventricle (LV) function are, however, not clear in two phenotypes of HCM, namely, obstructive and non-obstructive. To address this issue, we developed patient-specific computational models of the LV using clinical measurements from 2 female HCM patients and a control subject. Left ventricular mechanics was described using an active stress formulation and myofiber disarray was described using a structural tensor in the constitutive models. Unloaded LV configuration for each subject was first determined from their respective end-diastole LV geometries segmented from the cardiac magnetic resonance images, and an empirical single-beat estimation of the end-diastolic pressure volume relationship. The LV was then connected to a closed-loop circulatory model and calibrated using the clinically measured LV pressure and volume waveforms, peak GLS and blood pressure. Without consideration of myofiber disarray, peak myofiber tension was found to be lowest in the obstructive HCM subject (60 kPa), followed by the non-obstructive subject (242 kPa) and the control subject (375 kPa). With increasing myofiber disarray, we found that peak tension has to increase in the HCM models to match the clinical measurements. In the obstructive HCM patient, however, peak tension was still depressed (cf. normal subject) at the largest degree of myofiber disarray found in the clinic. The computational modeling workflow proposed here can be used in future studies with more HCM patient data.


Assuntos
Cardiomiopatia Hipertrófica , Ventrículos do Coração , Feminino , Humanos , Cardiomiopatia Hipertrófica/patologia , Função Ventricular Esquerda/fisiologia
3.
Huan Jing Ke Xue ; 44(1): 94-103, 2023 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-36635799

RESUMO

Quzhou county is a county in the North China Plain with intensive agricultural production. Based on data collected on the local anthropogenic activity level and the ammonia (NH3) emission factor, the anthropogenic NH3 emission inventory in Quzhou county from 2002 to 2019 was established using the emission factor method, and the NH3 emission inventory in 2019 was optimized using the locally measured nitrogen (N) fertilizer application NH3 emission factor and activity data from farmer surveys. We found that the total NH3 emission in Quzhou county showed a bimodal pattern: it increased from 6682.9 t in 2002 to 7195.0 t in 2004 and then decreased to 5872.0 t in 2008. The second peak occurred in 2015 (7010.5 t) and then gradually decreased to 5636.3 t in 2018. Livestock husbandry (61%-75%) and N fertilizer application (14%-28%) were the primary NH3 emission sources. In 2019, the total NH3 emission in Quzhou county was 6559.7 t, of which N fertilizer application and livestock husbandry contributed 28% and 61%, respectively. Wheat planting contributed the highest NH3 emissions, accounting for 40% of the total NH3 emission of crop production. Laying hens had the largest NH3 emission in livestock production, contributing 40% of the total emissions. NH3 emissions were higher in the south than those in the north at the county level, with the average NH3 emission intensity reaching 13.5 t·km-2. Nanliyue and Baizhai towns were hot spots of NH3 emission. Taken together NH3 emission reduction in wheat production and layer hen breeding will help to control atmospheric NH3 pollution in the North China Plain.


Assuntos
Poluentes Atmosféricos , Animais , Feminino , Poluentes Atmosféricos/análise , Galinhas , Amônia/análise , Fertilizantes/análise , Agricultura , China , Gado , Nitrogênio/análise , Triticum
4.
Org Biomol Chem ; 21(3): 494-498, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36516063

RESUMO

Here we developed an efficient Ni-catalyzed C-F bond phosphorylation of aryl fluorides via the crucial intermediates of P-P(O) and P(O)OR. P-P(O) mediated organophosphorus generation is observed for active aryl fluorides, whereas inactive aryl fluorides can also be activated and phosphorylated via a P(O)OR-mediated pathway, which is barely reported yet. Facile scale-up to the gram level and the upgrading of the bioactive molecule make this protocol to have promising applications in synthetic chemistry.


Assuntos
Fluoretos , Catálise
5.
Pharmacol Biochem Behav ; 222: 173510, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36565790

RESUMO

Nicotine is an addictive compound that interacts with nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA), inducing a release of dopamine in the nucleus accumbens (NAc). When neurons undergo repeated exposure to nicotine, several adaptive changes in neuroplasticity occur. Activation of nAChRs involves numerous intracellular signaling cascades that likely contribute to neuroplasticity and ultimately the establishment of nicotine addiction. Nevertheless, the molecular mechanisms underlying this adaptation remain unclear. To explore the effects of nicotine on neuroplasticity, a stable nicotine-induced conditioned place preference (CPP) model was constructed by intravenous injection in mice. Using a PCR array, we observed significant changes in the expression of synaptic plasticity-related genes in the VTA (16 mRNAs) and NAc (40 mRNAs). When mice were pre-treated with PD98059, an extracellular signal-regulated kinase (ERK) inhibitor, more gene expression changes in the VTA (53 mRNAs) and NAc (60 mRNAs) were found. Moreover, PD98059 pre-treatment blocked the increased p-ERK/ERK and p-CREB/CREB ratios and decreased the expression of synaptic plasticity-related proteins such as SAP102, PSD95, synaptophysin, and BDNF, these changes might contribute to preventing the establishment of nicotine-induced CPP. Furthermore, neurons from the VTA and NAc of nicotine CPP mice had an increased dendritic spine density and complexity of dendritic morphology by Golgi staining. PD98059 also blocked this dynamic. These results demonstrate that repeated exposure to nicotine may remold the expression of neuroplasticity-related genes by activating the ERK signaling pathway in the VTA and NAc, and is related to the establishment of nicotine-induced CPP.


Assuntos
Nicotina , Receptores Nicotínicos , Camundongos , Masculino , Animais , Nicotina/farmacologia , Nicotina/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Recompensa , Transdução de Sinais , Núcleo Accumbens/metabolismo , Área Tegmentar Ventral/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Plasticidade Neuronal
6.
J Colloid Interface Sci ; 633: 657-667, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36473356

RESUMO

Melanoma is an aggressive tumor located in skin with high rates of recurrence and metastasis. Due to the limited traditional therapies, the development of novel strategies against melanoma is urgently quested. To reduce the side effects of traditional administration ways and amplify the killing effect, an injectable sodium alginate (SA)-based hydrogels were developed, in which CaCO3/polydopamine nanoparticles (CaCO3/PDA NPs) were embedded for the synergistic photothermal/calcium ions interference therapy of melanoma. In the study, the formation conditions and mechanical properties of CaCO3/PDA-SA hydrogels were characterized, and their antitumor efficiency and mechanism against mouse melanoma cells were investigated. Wheninjectedintratumorally, CaCO3/PDA-SA fluid was converted into hydrogel in situ through the interaction of pH-sensitive released Ca2+ and alginate chains, which increased the retention time of photothermal agents (CaCO3/PDA NPs) at tumor sites and thereby was more conducive to produce hyperthermia via photothermal conversion to combat melanoma. Moreover, in acidic tumor microenvironment, the residual CaCO3/PDA NPs in hydrogels continuously decomposed and released Ca2+ to destroy the Ca2+ buffering capacity and evoke the mitochondrial Ca2+-overloading, resulting in the inhibition of adenosine triphosphate production to accelerate cell death. Notably, besides the heat elevation, the near-infrared light (NIR) irradiation would further enhance the release of Ca2+ to promote the Ca2+-involved cell death. Therefore, a pH/NIR-responsive and injectable SA-based hydrogels were successfully established and showed enhanced treatment efficacy of melanoma through the synergism of photothermal therapy and calcium ions interference therapy.

7.
Plant Biotechnol J ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36458856

RESUMO

Recombination is crucial for crop breeding because it can break linkage drag and generate novel allele combinations. However, the high-resolution recombination landscape and its driving forces in soybean are largely unknown. Here, we constructed 8 recombinant inbred line (RIL) populations and genotyped individual lines using the high-density 600K SoySNP array, which yielded a high-resolution recombination map with 5,636 recombination sites at a resolution of 1.37 kb. The recombination rate was negatively correlated with transposable element density and GC content but positively correlated with gene density. Interestingly, we found that meiotic recombination was enriched at the promoters of active genes. Further investigations revealed that chromatin accessibility and active epigenetic modifications promoted recombination. Our findings provide important insights into the control of homologous recombination and thus will increase our ability to accelerate soybean breeding by manipulating meiotic recombination rate.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36461925

RESUMO

Bioadhesives are widely used in a variety of medical settings due to their ease of use and efficient wound closure and repair. However, achieving both strong adhesion and removability/reusability is highly needed but challenging. Here, we reported an injectable mesoporous bioactive glass nanoparticle (MBGN)-incorporated biopolymer hydrogel bioadhesive that demonstrates a strong adhesion strength (up to 107.55 kPa) at physiological temperatures that is also removable and reusable. The incorporation of MBGNs in the biopolymer hydrogel significantly enhances the tissue adhesive strength due to an increased cohesive and adhesive property compared to the hydrogel adhesive alone. The detachment of bioadhesive results from temperature-induced weakening of interfacial adhesive strength. Moreover, the bioadhesive displays injectability, self-healing, and excellent biocompatibility. We demonstrate potential applications of the bioadhesive in vitro, ex vivo, and in vivo for hemostasis and intestinal leakage closure and accelerated skin wound healing compared to surgical wound closures. This work provides a novel design of strong and removable bioadhesives.

9.
Int J Gen Med ; 15: 8353-8363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465269

RESUMO

Coronavirus disease 2019 (COVID-19) remains an uncontained, worldwide pandemic. While battling the disease in China, the Chinese government has actively promoted the use of traditional Chinese medicine, and many studies have been conducted to determine the efficacy of traditional Chinese medicine for treating COVID-19. The present review discusses the effectiveness and safety of traditional Chinese medicine in curing COVID-19 and provides clinical evidence from all confirmed cases in China. Applications of traditional Chinese medicine and specific recipes for treating other viral infections, such as those caused by severe acute respiratory syndrome coronavirus and influenza A viruses (including H1N1), are also discussed. Studies have reported that traditional Chinese medicine treatment plays a significant role in improving clinical symptoms. Therefore, further investigation may be of high translational value in revealing novel targeted therapies for COVID-19.

10.
RSC Adv ; 12(52): 33988-34005, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36544995

RESUMO

The built-in distorted stress field of graphene (Gr) and its derivatives in defective state will induce local geometrical buckling due to the geometry of monatomic layer. The random distribution and types of functional groups (FGOs) and defects will have a significant impact on the stress accumulation and geometrical deformation of two-dimensional (2D) materials. By using molecular dynamics (MD), structure design and nonlinear mechanics theory, a new model (combining both planar 2D heterostructures and graphene oxide (GO)) was established to study geometrical effects, stress accumulation, bonding energies and mechanical properties of 2D interface (key point) at stress distortion field and accumulated stress field. The results show that grain boundaries (GBs), nanoholes and FGOs have different effects on the mechanical properties and out-of-plane deformation of 2D materials. By using Von-mises stresses and statistical mechanics, the geometrical effects, built-in distortion stress transfer and attenuation appeared in the each domain of 2D materials during the order-disorder transition processes. Moreover, there are two opposite aspects of stress accumulation, transmission, attenuation and geometrical effects of grain boundary (GBs), FGOs and nanoholes with distance. The ratio of strain energy (bond length and angle) is very sensitive to each domain of 2D materials. Finally, the 2D planar configuration gradually changes to a negative Gaussian surface, and the softening and weakening effects induced by GBs, nanoholes and FGOs are gradually enhanced. It is hoped that the current results can be used as a guide to adjust the geometry and stress accumulation of 2D materials in the new growth point.

11.
Front Bioeng Biotechnol ; 10: 1028691, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561042

RESUMO

Protein is one of the most important biological macromolecules in life, which plays a vital role in cell growth, development, movement, heredity, reproduction and other life activities. High quality isolation and purification is an essential step in the study of the structure and function of target proteins. Therefore, the development of protein purification technologies has great theoretical and practical significance in exploring the laws of life activities and guiding production practice. Up to now, there is no forthcoming method to extract any proteins from a complex system, and the field of protein purification still faces significant opportunities and challenges. Conventional protein purification generally includes three steps: pretreatment, rough fractionation, and fine fractionation. Each of the steps will significantly affect the purity, yield and the activity of target proteins. The present review focuses on the principle and process of protein purification, recent advances, and the applications of these technologies in the life and health industry as well as their far-reaching impact, so as to promote the research of protein structure and function, drug development and precision medicine, and bring new insights to researchers in related fields.

12.
Mol Biomed ; 3(1): 46, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36536188

RESUMO

Proteolysis targeting chimeras (PROTACs) technology has emerged as a novel therapeutic paradigm in recent years. PROTACs are heterobifunctional molecules that degrade target proteins by hijacking the ubiquitin-proteasome system. Currently, about 20-25% of all protein targets are being studied, and most works focus on their enzymatic functions. Unlike small molecules, PROTACs inhibit the whole biological function of the target protein by binding to the target protein and inducing subsequent proteasomal degradation. PROTACs compensate for limitations that transcription factors, nuclear proteins, and other scaffolding proteins are difficult to handle with traditional small-molecule inhibitors. Currently, PROTACs have successfully degraded diverse proteins, such as BTK, BRD4, AR, ER, STAT3, IRAK4, tau, etc. And ARV-110 and ARV-471 exhibited excellent efficacy in clinical II trials. However, what targets are appropriate for PROTAC technology to achieve better benefits than small-molecule inhibitors are not fully understood. And how to rationally design an efficient PROTACs and optimize it to be orally effective poses big challenges for researchers. In this review, we summarize the features of PROTAC technology, analyze the detail of general principles for designing efficient PROTACs, and discuss the typical application of PROTACs targeting different protein categories. In addition, we also introduce the progress of relevant clinical trial results of representative PROTACs and assess the challenges and limitations that PROTACs may face. Collectively, our studies provide references for further application of PROTACs.

13.
Int J Mol Sci ; 23(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36555571

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic disease manifested in hepatic steatosis, inflammation, fibrosis, etc., which affects over one-quarter of the population around the world. Since no effective therapeutic drugs are available to cope with this widespread epidemic, the functional research of genes with altered expression during NAFLD helps understand the pathogenesis of this disease and the development of new potential therapeutic targets for drugs. In the current work, we discovered via the analysis of the Gene Expression Omnibus (GEO) dataset that cysteine sulfinic acid decarboxylase (CSAD) decreased significantly in NAFLD patients, which was also confirmed in multiple NAFLD mouse models (HFD-fed C57BL/6J, db/db and HFHFrHC-fed C57BL/6J mice). Next, CSAD's function in the progression of NAFLD was explored using AAV-mediated liver-directed gene overexpression in an HFD-fed mouse model, where the overexpression of CSAD in the liver could alleviate NAFLD-associated pathologies, including body weight, liver/body weight ratio, hepatic triglyceride and total cholesterol, and the degree of steatosis. Mechanically, we found that the overexpression of CSAD could increase the expression of some genes related to fatty acid ß-oxidation (Acad1, Ppara, and Acox1). Furthermore, we also detected that CSAD could improve mitochondrial injury in vitro and in vivo. Finally, we proposed that the effect of CSAD on lipid accumulation might be independent of the taurine pathway. In conclusion, we demonstrated that CSAD is involved in the development of NAFLD as a protective factor, which suggested that CSAD has the potential to become a new target for drug discovery in NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Peso Corporal , Lipídeos/farmacologia , Metabolismo dos Lipídeos/genética
14.
Nutrients ; 14(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36501102

RESUMO

The placenta contains multiple biologically active substances, which exert antioxidation, anti-inflammatory, immunomodulatory, and delayed aging effects. Its extract can improve hepatic morphology and function: on the one hand, it can reduce liver interstitial collagen deposition, lipogenesis, and inflammatory cell infiltration and improve fibrosis; on the other hand, it can prevent hepatocellular degeneration by scavenging reactive oxygen species (ROS) and inhibiting inflammatory cytokine production, further improve hepatocyte apoptosis and necrosis, and promote hepatocyte regeneration, making it a promising liver-protective agent. Current research on placenta extract (PE) mainly focuses on treating a specific type of liver injury, and there are no systematic reports. Therefore, this review comprehensively summarizes the treatment reports of PE on liver injury and analyzes its mechanism of action.


Assuntos
Hepatopatias , Fígado , Gravidez , Feminino , Humanos , Fígado/metabolismo , Hepatócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Hepatopatias/metabolismo , Apoptose , Estresse Oxidativo
15.
Front Cell Neurosci ; 16: 998512, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439197

RESUMO

Background: 4-Hydroxynonenal (4-HNE), an α, ß-unsaturated hydroxyalkenal, has been found to be associated with aspirin resistance, which is a risk factor for recurrent cerebral infarction. However, its effect on recurrent cerebral infarction is less defined. We designed this study to investigate the association between 4-HNE and increased risk of recurrent cerebral infarction. Methods: We recruited 189 patients with primary cerebral infarction from 2017 to 2019. According to the recurrence of cerebral infarction during the 3-year follow-up period, they were divided into two groups, namely, the non-recurrence group (n = 93) and the recurrence group (n = 96). All patients were analyzed to explore the risk factors for the recurrence of primary cerebral infarction and the predictive value of serum 4-HNE for the recurrence of cerebral infarction. Results: The levels of serum 4-HNE in patients of the recurrence group were significantly higher than that in patients of the non-recurrence group. There was a positive correlation between serum 4-HNE levels and the serum levels of triglyceride (r = 0.448, p = 0.008) and low-density lipoprotein cholesterol (LDL-C; r = 0.442, p = 0.002) in primary cerebral infarction patients. Cox proportional hazards modeling showed that demographic and certain clinical parameters, such as age, serum triglyceride levels, the National Institutes of Health Stroke Scale (NIHSS) scores, and serum 4-HNE levels, were independent factors for the recurrence in patients. The results of the receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) value of serum 4-HNE in patients with cerebral infarction recurrence was 0.703, and when the cutoff value of serum 4-HNE was set at 42.34 ng/ml, the sensitivity and specificity values of serum 4-HNE in predicting recurrent cerebral infarction were 79.20 and 52.70%, respectively. Conclusion: Serum 4-HNE is an independent risk factor for the recurrence of patients with primary cerebral infarction, and it may become a new intervention way to prevent the recurrence of patients with cerebral infarction.

16.
Ann Med ; 54(1): 2951-2965, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36382675

RESUMO

BACKGROUND: Cytopenia is one of the most common adverse events following the CAR-T cell infusion, affecting the quality of life and potentially leading to life-threatening bleeding and infection. This study aimed to systematically review the cytopenias following anti-CD19 CAR-T therapy and further analyse the contributing factors. METHODS: Databases including PubMed, MEDLINE, Embase and Cochrane were systematically searched on 8 May 2022. A random-effect meta-analysis was used to estimate the incidence of cytopenia, and subgroup analyses were applied to explore heterogeneity. RESULTS: A total of 68 studies involving 2950 patients were included in this study. The overall incidence of all grade anaemia, thrombocytopenia, neutropenia, leukopoenia, lymphocytopenia and febrile neutropenia was 65%, 55%, 78%, 62%, 70% and 27%, respectively, and the corresponding cytopenias of grade 3 or worse were 33%, 31%, 61%, 45%, 46%, and 21%, respectively. Subgroup analysis showed increased incidence of cytopenias in subgroups with lower median age, proportion of males (<65%) and proportion of bridging therapy (<80%) and in the subgroup with a median line of prior therapy ≥3. In terms of disease and therapeutic target, cytopenias were more frequent in ALL patients and in dual-target CAR-T therapies (targeting CD19 in combination with other targets). Furthermore, CAR-T products manufactured by lentiviral vectors and those with the costimulatory domain of CD28 were more likely to cause haematological toxicity. No significant differences were observed in cytopenia between patients treated with CAR-T products with murine and humanized scFv. CONCLUSION: In conclusion, neutropenia is the most frequent cytopenia after CAR-T therapy, both in all grades or grade ≥3. The incidence of cytopenias following CAR-T therapy is influenced by the age, sex, disease and number of prior therapy lines of the patients, as well as the target and costimulatory domain of CAR-T cells, and viral vectors used for manufacturing.KEY MESSAGESNeutropenia is the most frequent cytopenia after CAR-T therapy.The clinical characteristics of the patients, the design of CAR-T cells and the protocol of CAR-T treatment can influence the occurrence of cytopenias following the CAR-T therapy.


Assuntos
Anemia , Neutropenia , Receptores de Antígenos Quiméricos , Trombocitopenia , Masculino , Humanos , Camundongos , Animais , Qualidade de Vida , Antígenos CD19/uso terapêutico , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Trombocitopenia/terapia , Neutropenia/epidemiologia , Neutropenia/etiologia , Neutropenia/tratamento farmacológico , Terapia Baseada em Transplante de Células e Tecidos
17.
Chem Biol Interact ; 369: 110265, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36375515

RESUMO

Irisin, a muscle-secreted cytokine involved in maintaining glucose homeostasis and improving insulin resistance, is generated from the precursor fibronectin type Ⅲ domain-containing protein 5 (FNDC5) by specific proteases. Zinc-finger protein Zfp57, a transcription factor that maintains the methylation during early embryonic development, is also reported to be associated with diabetes mellitus. However, the association between Zfp57 and FNDC5 is still unclear. In our study, we explored the detailed regulatory effect of Zfp57 on FNDC5 expression. In this study, we found that high-fat diet or saturated fatty acid palmitate increased the Zfp57 expression and decreased FNDC5 expression in muscle tissue or C2C12 myotubes. RNA sequencing analysis disclosed effects of the high-fat diet on genes associated with insulin resistance and the AMP-activated protein kinase (AMPK) signaling pathway in muscle tissue of mice. Chromatin immunoprecipitation experiments revealed that Zfp57 binds the FNDC5 gene promoter at positions -308 to -188. Moreover, Zfp57 overexpression inhibited FNDC5 expression, and Zfp57 knockdown alleviated the inhibitory effect of palmitate on FNDC5 expression in C2C12 myotubes. In addition, in vivo and in vitro studies demonstrated that activation of the AMPK pathway by 5-Aminoimidazole-4-carboxamide riboside (AICAR) or metformin mitigated the inhibitory effect of Zfp57 on FNDC5 expression and improved insulin resistance. These findings collectively suggest that high-fat diet and palmitate inhibit the AMPK pathway to increase Zfp57 expression, which in turn induces FNDC5 inhibition, to further aggravate insulin resistance.

18.
ACS Nano ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36412574

RESUMO

Preventing local tumor recurrence and simultaneously improving bone-tissue regeneration are in great demand for osteosarcoma therapy. However, the current therapeutic implants fail to selectively suppress tumor growth and enhance osteogenesis, and antitumor therapy may compromise osseointegration of the bone implant. Here, based on the different responses of bone tumor cells and osteoblasts to different electric stimulations, we constructed ferroelectric BaTiO3 nanorod arrays (NBTO) on the surface of titanium implants with switchable dynamic and static electrical stimulation for selective bone-tumor therapy and bone tissue regeneration. Polarized NBTO (PNBTO) generated a sustained dynamic electrical stimulus in response to wireless ultrasonic irradiation ("switch-on"), which disrupted the orientation of the spindle filaments of the tumor cell, blocked the G2/M phase of mitosis, and ultimately led to tumor cell death, whereas it had almost no cytotoxic effect on normal bone cells. Under the switch-off state, PNBTO with a high surface potential provided static electrical stimulation, accelerating osteogenic differentiation of mesenchymal stem cells and enhancing the quality of bone regeneration both in vitro and in vivo. This study broadens the biomedical potential of electrical stimulation therapy and provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration in osteosarcoma.

19.
Nutrients ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364921

RESUMO

Placental extract has been used for skin care and delaying skin aging. Cow placenta is an abundant resource with a large mass, which has not been harnessed effectively. Cow placenta extract (CPE) has the functions of antioxidation, anti-inflammatory, promoting growth and development, and promoting hair growth. However, little is known about the effect of oral administration of cow placenta extract on skin conditions. Therefore, the present study aimed to investigate the antioxidant capacity of CPE in vitro and in vivo and its protective effect on d-galactose (D-gal) induced skin aging in mice. The results showed that CPE had strong free radical scavenging, reducing and metal chelating activities. CPE can increase the activity of catalase (CAT), glutathione peroxidase (GSH-Px), peroxidase (POD), superoxide dismutase (SOD), and the content of glutathione (GSH), decrease the content of malondialdehyde (MDA). Moreover, CPE can decrease the gene and protein expression of matrix metalloproteinase 1a (MMP-1a) and matrix metalloproteinase 3 (MMP-3) and increase the expression of transforming growth factor-ß (TGF-ß) and tissue inhibitor of metalloproteinase 1 (TIMP-1) of mouse skin. Histopathological analysis showed CPE reduced the collagen damage caused by D-gal, increased collagen synthesis and reduced its degradation to delay skin aging.


Assuntos
Antioxidantes , Envelhecimento da Pele , Animais , Bovinos , Feminino , Camundongos , Gravidez , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Galactose/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo , Placenta/metabolismo , Extratos Vegetais/farmacologia , Superóxido Dismutase/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo
20.
Comput Methods Programs Biomed ; 227: 107188, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36334525

RESUMO

BACKGROUND AND OBJECTIVE: The myocardial demand-supply feedback system plays an important role in augmenting blood supply in response to exercise-induced increased myocardial demand. During this feedback process, the myocardium and coronary blood flow interact bidirectionally at many different levels. METHODS: To investigate these interactions, a novel computational framework that considers the closed myocardial demand-supply feedback system was developed. In the framework coupling the systemic circulation of the left ventricle and coronary perfusion with regulation, myocardial work affects coronary perfusion via flow regulation mechanisms (e.g., metabolic regulation) and myocardial-vessel interactions, whereas coronary perfusion affects myocardial contractility in a closed feedback system. The framework was calibrated based on the measurements from healthy subjects under graded exercise conditions, and then was applied to simulate the effects of graded exercise on myocardial demand-supply under different physiological and pathological conditions. RESULTS: We found that the framework can recapitulate key features found during exercise in clinical and animal studies. We showed that myocardial blood flow is increased but maximum hyperemia is reduced during exercise, which led to a reduction in coronary flow reserve. For coronary stenosis and myocardial inefficiency, the model predicts that an increase in heart rate is necessary to maintain the baseline cardiac output. Correspondingly, the resting coronary flow reserve is exhausted and the range of heart rate before exhaustion of coronary flow reserve is reduced. In the presence of metabolic regulation dysfunction, the model predicts that the metabolic vasodilator signal is higher at rest, saturates faster during exercise, and as a result, causes quicker exhaustion of coronary flow reserve. CONCLUSIONS: Model predictions showed that the coronary flow reserve deteriorates faster during graded exercise, which in turn, suggests a decrease in exercise tolerance for patients with stenosis, myocardial inefficiency and metabolic flow regulation dysfunction. The findings in this study may have clinical implications in diagnosing cardiovascular diseases.


Assuntos
Circulação Coronária , Estenose Coronária , Animais , Circulação Coronária/fisiologia , Retroalimentação , Miocárdio , Simulação por Computador
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