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1.
Bioact Mater ; 19: 75-87, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35441117

RESUMEN

Osteoporosis is one of the most disabling consequences of aging, osteoporotic fractures and higher risk of the subsequent fractures leading to substantial disability and deaths, indicating both local fractures healing and the early anti-osteoporosis therapy are of great significance. Teriparatide is strong bone formation promoter effective in treating osteoporosis, while side effects limit clinical applications. Traditional drug delivery is lack of sensitive and short-term release, finding a new non-invasive and easily controllable drug delivery to not only repair the local fractures but also improve total bone mass has remained a great challenge. Thus, bioinspired by the natural bone components, we develop appropriate interactions between inorganic biological scaffolds and organic drug molecules, achieving both loaded with the teriparatide in the scaffold and capable of releasing on demand. Herein, biomimetic bone microstructure of mesoporous bioglass, a near-infrared ray triggered switch, thermosensitive liposomes based on a valve, and polydopamine coated as a heater is developed rationally for osteoporotic bone regeneration. Teriparatide is pulsatile released from intelligent delivery, not only rejuvenating osteoporotic bone defect, but also presenting strong systemic anti-osteoporosis therapy. This biomimetic bone carrying novel drug delivery platform is well worth expecting to be a new promising strategy and clinically commercialized to help patients survive from the osteoporotic fracture.

2.
Front Pharmacol ; 13: 841330, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35496300

RESUMEN

Background: Doxorubicin (DOX) has been widely used in cancer treatment. However, DOX can cause a range of significant side effects, of which hepatotoxicity is a common one, and therefore limits its clinical use. Pterostilbene (PTS) has been shown to exhibit anti-oxidant and anti-inflammatory effects in the treatment of liver diseases but whether PTS could protect against hepatotoxicity in DOX-treated mice is unknown. Methods: In our study, we use C57/BL6J mice and the HepG2 cell line. We divided the mice in 4 groups: the control, the PTS treatment, the DOX treatment, and the DOX + PTS treatment group. Liver histopathology was judged by performing hematoxylin-eosin and Masson staining. Immunohistochemistry was used to perform the expression of NLRP3. The levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) were evaluated. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and DCFH-DA staining were used to evaluate the oxidative injury. Western blot and real-time PCR were applied to evaluate the expressions of proteins and mRNA. MTT was used to evaluate DOX-induced cell injury and the protective effects of PTS. Recombinant Trx-1 was used to analyze the mechanism of PTS. A TUNEL assay was used to detect apoptosis in DOX-induced HepG2 cells and the protective effects of PTS. Results: PTS ameliorated DOX-induced liver pathological changes and the levels of AST and ALT. PTS also decreased the level of MDA, increased the level of SOD, GSH, and the expression of Trx-1 in DOX-treated mice. PTS decreased the levels of NLRP3 and IL-1ß mRNA and the expressions of their proteins in DOX-treated mice. In addition, PTS also decreased the expression of Cleaved Caspase-3 and BAX and increased the expression of BCL-2. In vitro, after treatment with recombinant Trx-1, ROS and NLRP3 inflammasome were both decreased. Treatment with PTS could rescue the downregulation of Trx-1, decreased the ROS level and the NLRP3 inflammasome, and protected HepG2 cells against DOX-induced apoptosis. Conclusion: The results show that PTS exhibits protective effects against DOX-induced liver injuries via suppression of oxidative stress, fibrosis, NLRP3 inflammasome stimulation, and cell apoptosis which might lead to a new approach of preventing DOX-induced hepatotoxicity.

3.
Gen Psychiatr ; 35(1): e100751, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35372787

RESUMEN

China's population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated, especially Alzheimer's disease (AD) and related dementias (ADRD). AD's incidence rate, morbidity, and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals, families and society. The 'Healthy China Action' plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD. This report describes related epidemiological trends, evaluates the economic burden of the disease, outlines current clinical diagnosis and treatment status and delineates existing available public health resources. More specifically, it examines the public health impact of ADRD, including prevalence, mortality, costs, usage of care, and the overall effect on caregivers and society. In addition, this special report presents technical guidance and supports for the prevention and treatment of AD, provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.

4.
Cell Mol Biol Lett ; 27(1): 2, 2022 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-34979914

RESUMEN

Sestrins (Sesns), highly conserved stress-inducible metabolic proteins, are known to protect organisms against various noxious stimuli including DNA damage, oxidative stress, starvation, endoplasmic reticulum (ER) stress, and hypoxia. Sesns regulate metabolism mainly through activation of the key energy sensor AMP-dependent protein kinase (AMPK) and inhibition of mammalian target of rapamycin complex 1 (mTORC1). Sesns also play pivotal roles in autophagy activation and apoptosis inhibition in normal cells, while conversely promoting apoptosis in cancer cells. The functions of Sesns in diseases such as metabolic disorders, neurodegenerative diseases, cardiovascular diseases, and cancer have been broadly investigated in the past decades. However, there is a limited number of reviews that have summarized the functions of Sesns in the pathophysiological processes of human diseases, especially musculoskeletal system diseases. One aim of this review is to discuss the biological functions of Sesns in the pathophysiological process and phenotype of diseases. More significantly, we include some new evidence about the musculoskeletal system. Another purpose is to explore whether Sesns could be potential biomarkers or targets in the future diagnostic and therapeutic process.


Asunto(s)
Proteínas Nucleares , Sestrinas , Autofagia , Proteínas de Choque Térmico/metabolismo , Humanos , Proteínas Nucleares/metabolismo , Estrés Oxidativo/fisiología , Transducción de Señal/fisiología
5.
Int J Biol Sci ; 18(7): 2882-2897, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35541895

RESUMEN

Cold-inducible RNA-binding protein (CIRBP) is documented to be required for maintaining cardiac function, however, its role in chemotherapy-induced cardiotoxicity remains obscured. Herein, we report that CIRBP decreases cardiomyocyte apoptosis and attenuates cardiotoxicity through disrupting OGF-OGFR signal. CIRBP deficiency is involved in diverse chemotherapeutic agents induced cardiomyocyte apoptosis. Delivery of exogenous CIRBP to the mouse myocardium significantly mitigated doxorubicin-induced cardiac apoptosis and dysfunction. Specifically, OGFR was identified as a downstream core effector responsible for chemotherapy-induced cardiomyocyte apoptosis. CIRBP was shown to interact with OGFR mRNA and to repress OGFR expression by reducing mRNA stability. CIRBP-mediated cytoprotection against doxorubicin-induced cardiac apoptosis was demonstrated to largely involve OGFR repression by CIRBP. NTX as a potent antagonist of OGFR successfully rescued CIRBP ablation-rendered susceptibility to cardiac dyshomeostasis upon exposure to doxorubicin, whereas another antagonist ALV acting only on opioid receptors did not. Taken together, our results demonstrate that CIRBP confers myocardium resistance to chemotherapy-induced cardiac apoptosis and dysfunction by dampening OGF/OGFR axis, shedding new light on the mechanisms of chemo-induced cardiotoxicity and providing insights into the development of an efficacious cardioprotective strategy for cancer patients.


Asunto(s)
Cardiotoxicidad , Doxorrubicina , Encefalina Metionina , Animales , Apoptosis/efectos de los fármacos , Cardiotoxicidad/etiología , Cardiotoxicidad/metabolismo , Cardiotoxicidad/patología , Proliferación Celular , Doxorrubicina/toxicidad , Encefalina Metionina/metabolismo , Encefalina Metionina/farmacología , Humanos , Ratones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Proteínas de Unión al ARN/genética
6.
Artículo en Inglés | MEDLINE | ID: mdl-35561839

RESUMEN

BACKGROUND: The mitochondrial fission protein, dynamin related protein 1 (Drp1), has been suggested to regulate mast cell (MC) activation by certain stimuli in vitro but its functions in MCs activated by various stimuli in vivo has not been examined. OBJECTIVE: Analyze Drp1 function in both mouse and human MCs. METHODS: We used human peripheral blood-derived cultured MCs (PBCMCs) and two genetic mouse models in which MCs were depleted of Drp1: Drp1fl/flMcpt5cre+/- mice and Drp1fl/flCpa3cre+/- mice. RESULTS: In mice, Drp1 depletion enhanced FcεRI-induced MC activation while suppressing substance P (SP)-stimulated MC activation in vitro and in vivo. This was also true in human PBCMCs in vitro after pharmacological inhibition of Drp1. CONCLUSION: Our work shows that Drp1 differentially regulates MC activation by various stimuli. These findings suggest that promoting Drp1 activation might represent a novel therapy for suppressing IgE-dependent MC activation while inhibiting Drp1 activation might mitigate other MC-dependent responses, such as those induced by substance P.

7.
Plant Cell ; 2022 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-35567529

RESUMEN

Signaling by the evolutionarily conserved mitogen-activated protein kinase or extracellular signal-regulated kinase (MAPK/ERK) plays critical roles in converting extracellular stimuli into immune responses. However, whether MAPK/ERK signaling induces virus immunity by directly phosphorylating viral effectors remains largely unknown. Barley yellow striate mosaic virus (BYSMV) is an economically important plant cytorhabdovirus that is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus) in a propagative manner. Here, we found that the barley (Hordeum vulgare) MAPK MPK3 (HvMPK3) and the planthopper ERK (LsERK) proteins interact with the BYSMV nucleoprotein (N) and directly phosphorylate N protein primarily on serine 290. Overexpression of HvMPK3 inhibited BYSMV infection, whereas barley plants treated with the MAPK pathway inhibitor U0126 displayed greater susceptibility to BYSMV. Moreover, knockdown of LsERK promoted virus infection in SBPHs. A phosphomimetic mutant of the N Ser290 (S290D) completely abolished virus infection because of impaired self-interaction of BYSMV N and formation of unstable N-RNA complexes. Altogether, our results demonstrate that the conserved MAPK and ERK directly phosphorylate the viral nucleoprotein to trigger immunity against cross-kingdom infection of BYSMV in host plants and its insect vectors.

8.
Phys Rev Lett ; 128(16): 163602, 2022 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-35522487

RESUMEN

We demonstrate that stimulated microwave optical sideband generation using parametric frequency conversion can be utilized as a powerful technique for coherent state detection in atomic physics experiments. The technique has advantages over traditional absorption or polarization rotation-based measurements and enables the isolation of signal photons from probe photons. We outline a theoretical framework that accurately models sideband generation using a density matrix formalism. Using this technique, we demonstrate a novel intrinsic magnetic gradiometer that detects magnetic gradient fields between two spatially separated vapor cells by measuring the frequency of the beat note between sidebands generated within each cell. The sidebands are produced with high efficiency using parametric frequency conversion of a probe beam interacting with ^{87}Rb atoms in a coherent superposition of magnetically sensitive hyperfine ground states. Interference between the sidebands generates a low-frequency beat note whose frequency is determined by the magnetic field gradient between the two vapor cells. In contrast to traditional gradiometers the intermediate step of measuring the magnetic field experienced by the two vapor cells is unnecessary. We show that this technique can be readily implemented in a practical device by demonstrating a compact magnetic gradiometer sensor head with a sensitivity of 25 fT/cm/sqrt[Hz] with a 4.4 cm baseline, while operating in a noisy laboratory environment unshielded from Earth's field.

9.
Jpn J Clin Oncol ; 2022 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-35532291

RESUMEN

BACKGROUND: Few studies have focused on DNA methylation in endometrial cancer. The aim of our study is identify its role in endometrial cancer prognosis. METHODS: A publicly available dataset was retrieved from The Cancer Genome Atlas. For validation of expression alteration due to methylation, RNA sequencing data were obtained from other independent cohorts. MethSurv was used to search for candidate CpG probes, which were then filtered by least absolute shrinkage and selection operator Cox regression and multivariate Cox regression analyses to identify final set of CpG probes for overall survival. A methylation-based risk model was developed and receiver operating characteristic analysis with area under curve was used for evaluation. Patients were divided into high- and low-risk groups using an optimal cut-off point. Comprehensive bioinformatic analyses were conducted to identify hub genes, key transcription factors, and enriched cancer-related pathways. Kaplan-Meier curve was used for survival analysis. RESULTS: A 5-CpG signature score was established. Its predictive value for 5-year overall survival was high, with area under curve of 0.828, 0.835 and 0.816 for the training, testing and entire cohorts. cg27487839 and cg12885678 had strong correlation with their gene expression, XKR6 and PTPRN2, and lower PTPRN2 expression was associated with poorer survival in both The Cancer Genome Atlas and the validation datasets. Low-risk group was associated with significantly better survival. Low-risk group harboured more mutations in hub genes and key transcription factors, and mutations in SP1 and MECP2 represented favourable outcome. CONCLUSION: We developed a methylation-based prognostic stratification system for endometrial cancer. Low-risk group was associated with better survival and harboured more mutations in the key regulatory genes.

10.
Ying Yong Sheng Tai Xue Bao ; 33(3): 671-676, 2022 Mar.
Artículo en Chino | MEDLINE | ID: mdl-35524518

RESUMEN

Clarifying the differences of maize yield and its stability under long-term no-tillage with different stover mulching amounts can provide theoretical and technical supports for establishing and evaluating long-term conservation tillage pattern and promoting grain production. Based on a long-term conservation tillage field experiment in the mollisol area of Northeast China since 2007, we analyzed the interannual variation, variation coefficient and stability of maize yield during 2013 and 2019 across five treatments, i.e., no-tillage stover-free mulching (NT0), no-tillage with 33% stover mulching (NT33), no-tillage with 67% stover mulching (NT67) and no-tillage with 100% stover mulching (NT100), with the traditional ridge cropping (RT) as the control. The results showed that compared with RT, long-term no-tillage with stover mulching treatments could increase maize yield. NT100 had the highest increasing rate of 11.4%, followed by NT67 and NT0, with the increasing rate of 11.0% and 10.4%, respectively. Maize yield exhibited a nonlinear relationship with the amount of stover mulch. The variation coefficient of maize yield under multi-year no-tillage with different stover mulching could be sorted as NT67NT0>NT100>RT>NT33, indicating that NT67 treatment could significantly reduce the interannual fluctuation of maize yield and had better sustainability of yield. No-tillage stover mulching significantly increased soil total carbon and total nitrogen contents, which were significantly positively correlated with maize yield. In conclusion, compared with traditional tillage, no-tillage stover mulching could increase maize yield and soil carbon and nitrogen contents. Appropriate stover mulching (NT67)had the potential to improve the stability and sustainability of maize yield.


Asunto(s)
Agricultura , Zea mays , Agricultura/métodos , Carbono , China , Nitrógeno/análisis , Suelo
11.
Methods Enzymol ; 667: 685-727, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35525559

RESUMEN

Kinase inhibition continues to be a major focus of pharmaceutical research and discovery due to the central role of these proteins in the regulation of cellular processes. One family of kinases of pharmacological interest, due to its role in activation of immunostimulatory pathways, is the Janus kinase family. Small molecule inhibitors targeting the individual kinase proteins within this family have long been sought-after therapies. High sequence and structural similarity of the family members makes selective inhibitors difficult to identify but critical because of their inter-related multiple cellular regulatory pathways. Herein, we describe the identification of inhibitors of the important Janus kinase, TYK2, a regulator of type I interferon response. In addition, the biochemical and structural confirmation of the direct interaction of these small molecules with the TYK2 pseudokinase domain is described and a potential mechanism of allosteric regulation of TYK2 activity through stabilization of the pseudokinase domain is proposed.


Asunto(s)
Quinasas Janus , TYK2 Quinasa , Regulación Alostérica , Quinasas Janus/metabolismo , Transducción de Señal , TYK2 Quinasa/química , TYK2 Quinasa/metabolismo
12.
Mitochondrial DNA B Resour ; 7(5): 719-721, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35528251

RESUMEN

Pithecellobium clypearia (Jack) Benth. 1844 belongs to the genus Pithecellobium in the family Fabaceae. The complete chloroplast genome of P. clypearia was sequenced and analyzed by Illumina sequencing in this study. The full length of the complete chloroplast genome is 176,770 bp, containing a pair of inverted repeat regions of 39,693 bp (IRa and IRb) separated by a large single-copy (LSC) region of 92,500 bp and a small single-copy (SSC) region of 4,884 bp. The P. clypearia chloroplast genome encodes 137 genes, comprising 92 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on complete chloroplast genomes revealed that P. clypearia is closely related to Archidendron lucyi and Pithecellobium flexicaule. This study provides useful resources for further study and development of this species.

13.
Redox Biol ; 52: 102322, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35504134

RESUMEN

Mitochondrial dysfunction and oxidative stress-mediated inflammasome activation play critical roles in the pathogenesis of the non-alcoholic fatty liver disease (NAFLD). Non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1), or growth differentiation factor-15 (GDF15), is associated with many biological processes and diseases, including NAFLD. However, the role of NAG-1/GDF15 in regulating oxidative stress and whether this process is associated with absent in melanoma 2 (AIM2) inflammasome activation in NAFLD are unknown. In this study, we revealed that NAG-1/GDF15 is significantly downregulated in liver tissues of patients with steatosis compared to normal livers using the Gene Expression Omnibus (GEO) database, and in free fatty acids (FFA, oleic acid/palmitic acid, 2:1)-induced HepG2 and Huh-7 cellular steatosis models. Overexpression of NAG-1/GDF15 in transgenic (Tg) mice significantly alleviated HFD-induced obesity and hepatic steatosis, improved lipid homeostasis, enhanced fatty acid ß-oxidation and lipolysis, inhibited fatty acid synthesis and uptake, and inhibited AIM2 inflammasome activation and the secretion of IL-18 and IL-1ß, as compared to their wild-type (WT) littermates without reducing food intake. Furthermore, NAG-1/GDF15 overexpression attenuated FFA-induced triglyceride (TG) accumulation, lipid metabolism deregulation, and AIM2 inflammasome activation in hepatic steatotic cells, while knockdown of NAG-1/GDF15 demonstrated opposite effects. Moreover, NAG-1/GDF15 overexpression inhibited HFD- and FFA-induced oxidative stress and mitochondrial damage which in turn reduced double-strand DNA (dsDNA) release into the cytosol, while NAG-1/GDF15 siRNA showed opposite effects. The reduced ROS production and dsDNA release may be responsible for attenuated AIM2 activation by NAG-1/GDF15 upon fatty acid overload. In conclusion, our results provide evidence that other than regulating lipid homeostasis, NAG-1/GDF15 protects against hepatic steatosis through a novel mechanism via suppressing oxidative stress, mitochondrial damage, dsDNA release, and AIM2 inflammasome activation.


Asunto(s)
Factor 15 de Diferenciación de Crecimiento/metabolismo , Melanoma , Enfermedad del Hígado Graso no Alcohólico , Animales , ADN/metabolismo , Proteínas de Unión al ADN/metabolismo , Dieta Alta en Grasa , Ácidos Grasos/metabolismo , Ácidos Grasos no Esterificados/efectos adversos , Factor 15 de Diferenciación de Crecimiento/genética , Humanos , Inflamasomas/genética , Inflamasomas/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Melanoma/metabolismo , Ratones , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Estrés Oxidativo
14.
Technol Cancer Res Treat ; 21: 15330338221097215, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35491725

RESUMEN

Although the American Joint Commission on Cancer (AJCC) staging has been widely used to predict the survival of cancer patients, there are still some limitations. The high accuracy of lncRNA-based signature prediction has attracted widespread attention. The data were obtained from the RNA sequencing data of nonsmall cell lung cancer (NSCLC) in the Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) were identified. Using univariate Cox proportional hazard regression (CPHR) analysis, least absolute shrinkage and selection operator method, and multivariate CPHR, 5 lncRNAs (LINC00460, LINC00857, LINC01116, RP11-253E3.3, and RP11-359E19.2) related to patient survival were successfully screened. Combined with age, gender, AJCC staging, and 5 lncRNAs, a nomogram with a better prognosis prediction ability than traditional parameters was constructed. Prognostic accuracy was evaluated using the receiver operating characteristic (ROC) curve and area under the ROC value. In addition, through co-expression analysis, we found that 5 lncRNA target genes have 34 DEMs. Gene ontology function analysis showed that these DEMs were mainly enriched in enzyme inhibitor activity and other aspects. Finally, these DEMs were found to be involved in the formation of the tumor immune microenvironment. In short, the nomogram based on 5 lncRNAs can effectively predict the overall survival rate of NSCLC and may guide the formulation of treatment plans for NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , ARN Largo no Codificante , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Nomogramas , Pronóstico , ARN Largo no Codificante/genética , Microambiente Tumoral
15.
Int J Cardiol ; 2022 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-35490785

RESUMEN

BACKGROUND: Plaque rupture occurs when the structural stress inside plaques exceeds the capacity of the overlying fibrous cap. Plaque structural stress has been acknowledged as an index to evaluate the risk of plaque rupture. However, impacting factors associated with the level of plaque structural stress in ST-segment elevated myocardial infarction patients with ruptured plaques remain unknown. METHODS: Based on optical coherence tomography, we analyzed the plaque characteristics and calculated the maximal plaque stress of the culprit lesions in 162 patients with plaque rupture by performing finite element analysis. All enrolled patients were divided into two groups according to the level of maximal plaque stress. Cardiovascular risk factors, laboratory findings and clinical outcomes were compared between the two groups. RESULTS: Hemoglobin A1c (HbA1c) was significantly higher in the high stress group than in the low stress group (7.0% ± 1.8 vs. 6.3% ± 1.2, p = 0.003). The maximal plaque stress of patients with diabetes was significantly higher than that of patients without diabetes (538.7 kPa [346.2-810.6] vs. 425.9 kPa [306.2-571.4], p = 0.006). Moreover, the level of maximal plaque stress was significantly associated with HbA1c (Pearson's correlation coefficient: r = 0.289, P < 0.001). OCT findings showed that the fibrous cap thickness and maximal lipid arc were significantly associated with maximal plaque stress (r = -0.163, p = 0.038; r = 0.194, p = 0.013, respectively). CONCLUSION: OCT-based finite-element analysis showed that HbA1c was independently associated with the level of maximal plaque stress in STEMI patients with plaque rupture, thus indicating the importance of glucose control in patients with coronary atherosclerotic disease.

16.
Biomed Res Int ; 2022: 8557936, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35502338

RESUMEN

Objective: A case-control study was conducted to explore the effect of acupuncture combined with rehabilitation training on limb function and nerve injury rehabilitation in elderly patients with stroke. Methods: A total of 72 elderly patients with stroke treated from March 2019 to June 2021 in our hospital were enrolled as the object of study. The clinical data were collected and divided into two groups according to their different treatment methods. The patients cured with routine treatment combined with rehabilitation training were taken as the control group and the patients cured with acupuncture combined with rehabilitation training as the study group. The clinical efficacy was recorded, and the cognition and activities of daily living were evaluated by Terrell Cognitive Assessment scale, limb motor function score, and activities of daily living scale. The National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) were employed to compare the neurological function before and after treatment. Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS) were adopted to evaluate the functional prognosis. The simplified Fugl-Meyer assessment of motor recovery score was employed to evaluate the limb function of the patients. The Wolf Motor Function Test (WMFT) score was adopted to evaluate the functional rehabilitation effect of the patients. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the serum neurological function indexes such as nerve growth factor, Smur100B protein, and glial fibrillary acidic protein. The cerebral blood flow (CBF), peak time, average transit time, and cerebral blood volume were measured by CT perfusion imaging, and the incidence of side effects during treatment was recorded. Results: Regarding the recovery of cognitive function and daily function after treatment, after treatment, the MoCA and ADL scores were increased, and the comparison indicated that the MoCA and ADL scores of the study group were remarkably higher compared to the control group (P < 0.05). With regard to the FMA-UE scores after treatment, the Fugl-Meyer scores were gradually increased, and the Fugl-Meyer scores in the study group were remarkably higher compared to the control group (P < 0.05) in the next two months. After 2 weeks, 4 weeks, 6 weeks, and 6 weeks of treatment, the WMFT scores gradually increased, and the WMFT score of the study group was remarkably higher compared to the control group. After treatment, the levels of nerve growth factor and S-100B protein were decreased, and the level of glial fibrillary acidic protein was increased. Comparison between the two groups, it indicated the improvement degree of each neurological function index in the study group was remarkably better (P < 0.05). With regard to cerebral hemodynamic indexes after treatment, 1 week after treatment, the CBF and average transit time of the observation group were remarkably higher compared to the control group, and the levels of cerebral blood volume and peak time were remarkably lower compared to the control group (P < 0.05). After 4 weeks of treatment, the cerebral hemodynamic indexes of the observation group did not change remarkably, and they were all lower than 1 week after the treatment. In the terms of side effects, 1 case of limb dysfunction, 1 case of swallowing dysfunction, 1 case of electrolyte disturbance, and none of infection in the study group, the incidence of adverse reactions was 8.33%. In the control group, there were 3 cases of limb dysfunction, 2 cases of swallowing dysfunction, 2 cases of electrolyte disturbance, and 3 cases of infection, and the incidence of adverse reactions was 27.78%. Compared between groups, the incidence of adverse reactions in the study group was lower (P < 0.05). Conclusion: Early use of acupuncture combined with rehabilitation training has a remarkable therapeutic effect on elderly stroke patients. It can remarkably promote the recovery of the patient's condition, remarkably enhance their neurological function, cognitive function, motor function, and daily life function, and effectively strengthen the patient's prognosis score. It has important clinical application value to reduce the incidence of adverse reactions.


Asunto(s)
Terapia por Acupuntura , Accidente Cerebrovascular , Actividades Cotidianas , Anciano , Estudios de Casos y Controles , Electrólitos , Proteína Ácida Fibrilar de la Glía , Humanos , Factores de Crecimiento Nervioso , Estudios Retrospectivos , Estados Unidos
17.
Food Chem ; 386: 132776, 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-35509162

RESUMEN

Four types of pure lipid, namely lauric acid (LA), glycerol monolaurate (MAG), diglycerol laurate (DAG) and triglyceride laurate (TAG) were used to prepare oleofoams. The relationship between crystal profiles and their performance in oleofoams was established. DAG formed small needle-like crystals while MAG formed large flake-like crystals in oleogels, and crystal shells around air bubbles were observed in LA-, MAG- and DAG-based oleofoams. LA and DAG displayed higher over-run whereas DAG-stabilised foam possessed smaller bubbles and higher physical stability due to the presence of small ß and ß' crystals. Upon heating, DAG and TAG-based foams showed varying extents of oil drainage indicating the crystals were distributed in a different manner. Therefore, DAG was shown to be an excellent gelator in the fabrication of ultra-stable oleofoams. This work extends the lipid varieties with nutritional features and allows a better understanding on the stabilization mechanisms of lauric acid lipids in oleofoams.


Asunto(s)
Ésteres , Glicerol , Diglicéridos/química , Lauratos , Ácidos Láuricos
18.
Bioengineered ; 13(4): 11187-11207, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35510387

RESUMEN

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas, with high mortality and poor prognoses worldwide. Succinate dehydrogenase (SDH) consists of four nuclear-encoded subunits and it is the only complex involved in both the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). Previous studies have shown decreased SDH activity in ccRCC. However, the role and underlying molecular mechanisms of SDH in ccRCC initiation and development remain unclear. In the present study, pan-cancer analysis of SDH gene expression was analyzed and the relationship between SDH gene expression and clinicopathological parameters was assessed using different databases. cBioPortal, UACLAN, and Tumor Immune Estimation Resource (TIMER) were subsequently utilized to analyze genetic alterations, methylation, and immune cell infiltration of SDH genes in ccRCC patients. We found SDHs were significantly downregulated in ccRCC tissues and correlated with ccRCC progression. Increased methylation and high SDH promoter mutation rates may be the cause of reduced expression of SDHs in ccRCC. Moreover, the interaction network showed that SDH genes were correlated with ferroptosis-related genes. We further demonstrated that SDH inhibition dampened oxidative phosphorylation, reduced ferroptotic events, and restored ferroptotic cell death, characterized by eliminated mitochondrial ROS levels, decreased cellular ROS and diminished peroxide accumulation. Collectively, this study provides new insights into the regulatory role of SDH in the carcinogenesis and progression of ccRCC, introducing a potential target for advanced antitumor therapy through ferroptosis.


Asunto(s)
Carcinoma de Células Renales , Ferroptosis , Neoplasias Renales , Carcinogénesis/genética , Carcinoma de Células Renales/metabolismo , Femenino , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/metabolismo , Masculino , Especies Reactivas de Oxígeno/metabolismo , Succinato Deshidrogenasa/genética , Succinato Deshidrogenasa/metabolismo
19.
Nat Chem Biol ; 2022 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-35513512

RESUMEN

Lanthipeptides are an important group of natural products with diverse biological functions, and their biosynthesis requires the removal of N-terminal leader peptides (LPs) by designated proteases. LanPM1 enzymes, a subgroup of M1 zinc-metallopeptidases, have been recently identified as bifunctional proteases with both endo- and aminopeptidase activities to remove LPs of class III and class IV lanthipeptides. Herein, we report the biochemical and structural characterization of EryP as the LanPM1 enzyme from the biosynthesis of class III lanthipeptide erythreapeptin. We determined X-ray crystal structures of EryP in three conformational states, the open, intermediate and closed states, and identified a unique interdomain Ca2+ binding site as a regulatory element that modulates its domain dynamics and proteolytic activity. Inspired by this regulatory Ca2+ binding, we developed a strategy to engineer LanPM1 enzymes for enhanced catalytic activities by strengthening interdomain associations and driving the conformational equilibrium toward their closed forms.

20.
Plant J ; 2022 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-35514123

RESUMEN

Tomato has undergone extensive selections during domestication. Recent progress has shown that genomic structural variants (SVs) have contributed to gene expression dynamics during tomato domestication, resulting in changes of important traits. Here, we performed comprehensive analyses of small RNAs (sRNAs) from nine representative tomato accessions. We demonstrate that SVs substantially contribute to the dynamic expression of the three major classes of plant sRNAs: microRNAs (miRNAs), phased secondary short interfering RNAs (phasiRNAs), and 24-nt heterochromatic siRNAs (hc-siRNAs). Changes in the abundance of phasiRNAs and 24-nt hc-siRNAs likely contribute to the alteration of mRNA gene expression in cis during tomato domestication, particularly for genes associated with biotic and abiotic stress tolerance. We also observe that miRNA expression dynamics are associated with imprecise processing, alternative miRNA-miRNA* selections, and SVs. SVs mainly affect the expression of less-conserved miRNAs that do not have established regulatory functions or low abundant members in highly expressed miRNA families. Our data highlight different selection pressures on miRNAs compared to phasiRNAs and 24-nt hc-siRNAs. Our findings provide insights into plant sRNA evolution as well as SV-based gene regulation during crop domestication. Furthermore, our dataset provides a rich resource for mining the sRNA regulatory network in tomato.

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