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1.
Heliyon ; 10(12): e32727, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38994078

RESUMEN

Multiple cell death pathways are involved in neuronal death in ischemic stroke (IS). However, the role of different cell death pathways in different cell types has not been elucidated. By analyzing three single-nucleus RNA sequencing (snRNA-seq) data of IS, we first found that a variety of programmed cell death (PCD) -related genes were significantly changed in different cell types. Based on machine learning and virtual gene knockout, we found that ferroptosis related genes, ferritin heavy chain 1 (Fth1) and ferritin light chain (Ftl1), play a key role in IS. Ftl1 and Fth1 can promote microglia activation, as well as the production of inflammatory factors and chemokines. Cell communication analysis showed that activated microglia could enhance chemotactic peripheral leukocyte infiltration, such as macrophages and neutrophils, through Spp1-Cd44 and App-Cd74 signaling, thereby aggravating brain tissue damage. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) showed that P2ry12 and Mef2c were significantly decreased in oxygen-glucose deprivation (OGD) group, while Ftl1, Fth1, Apoe, Ctsb, Cd44 and Cd74 were significantly increased in OGD group. Collectively, our findings suggested targeted therapy against microglia Ftl1 and Fth1 might improve the state of microglia, reduce the infiltration of peripheral immune cells and tissue inflammation, and then improve the ischemic brain injury in mouse.

2.
FASEB J ; 38(2): e23387, 2024 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-38193649

RESUMEN

Human brain microvascular endothelial cells (HBMVECs) and microglia play critical roles in regulating cerebral homeostasis during ischemic stroke. However, the role of HBMVECs-derived exosomes in microglia polarization after stroke remains unknown. We isolated exosomes (Exos) from oxygen glucose deprivation (OGD)-exposed HBMVECs, before added them into microglia. Microglia polarization markers were tested using RT-qPCR or flow cytometry. Inflammatory cytokines were measured with ELISA. Endothelial cell damage was assessed by cell viability, apoptosis, apoptosis-related proteins, oxidative stress, and angiogenic activity using CCK-8, flow cytometry, western blot, ELISA, and endothelial tube formation assay, respectively. We also established middle cerebral artery occlusion (MCAO) mice model to examine the function of circ_0000495 on stroke in vivo. Our study found that HBMVECs-Exos reduced M2 markers (IL-10, CD163, and CD206), increased M1 markers (TNF-α, IL-1ß, and IL-12), CD86-positive cells, and inflammatory cytokines (TNF-α and IL-1ß), indicating the promotion of microglial M1-polarization. Microglial M1-polarization induced by HBMVECs-Exos reduced viability and promoted apoptosis and oxidative stress, revealing the aggravation of endothelial cell damage. However, circ_0000495 silencing inhibited HBMVECs-Exos-induced alterations. Mechanistically, circ_0000495 adsorbed miR-579-3p to upregulate toll-like receptor 4 (TLR4) in microglia; miR-579-3p suppressed HBMVECs-Exos-induced alterations via declining TLR4; furthermore, Yin Yang 1 (YY1) transcriptionally activated circ_0000495 in HBMVECs. Importantly, circ_0000495 aggravated ischemic brain injury in vivo via activating TLR4/nuclear factor-κB (NF-κB) pathway. Collectively, OGD-treated HBMVECs-Exos transmitted circ_0000495 to regulate miR-579-3p/TLR4/NF-κB axis in microglia, thereby facilitating microglial M1-polarization and endothelial cell damage.


Asunto(s)
Exosomas , MicroARNs , Accidente Cerebrovascular , Animales , Ratones , Humanos , Células Endoteliales , Microglía , Receptor Toll-Like 4/genética , FN-kappa B , Factor de Necrosis Tumoral alfa , Encéfalo , Hipoxia , Oxígeno , Citocinas , MicroARNs/genética
3.
World J Clin Cases ; 12(1): 76-85, 2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38292623

RESUMEN

BACKGROUND: Lung cancer is a common disease with high mortality, and psychological support is very important in the diagnosis and treatment of postoperative patients with cancer pain. AIM: To explore the application effect of the narrative nursing method in postoperative lung cancer patients in the intensive care unit. METHODS: A total of 120 patients diagnosed with lung cancer and experiencing cancer-related pain were randomly allocated into two groups: an observation group and a control group, each consisting of 60 cases. The control group was given routine analgesic and psychological care, while the research group applied the five-step narrative nursing method based on routine care, comparing the visual analogue scale scores, sleep status, anxiety and depression status, and quality of life of the two groups of patients before and after the intervention. RESULTS: The pain scores, anxiety scores, and depression scores of the study group were lower than those of the control group after the intervention using the narrative nursing method, and the difference was statistically significant (P < 0.05). CONCLUSION: Using narrative nursing methods to intervene in patients with lung cancer combined with cancerous pain can help patients to correctly recognize their disease, adjust their mentality, establish confidence, alleviate patients' subjective pain feelings, and improve their adverse emotions.

4.
Neuroscience ; 538: 95-109, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-37778691

RESUMEN

OBJECTIVE: Depression is a common mental illness. Neural stem cell-derived extracellular vesicles (NSC-EVs) are involved in repairing neuronal injury. We estimated the mechanism of miR-16-5p in depression rats. METHODS: EVs were extracted from NSCs. The depression rat model was established by corticosterone (CORT) induction and treated with NSC-EVs. The depression behavioral/pathological changes in rats were assessed using forced swimming test, open field test, sucrose consumption test and western blotting. The neuronal apoptosis in hippocampal tissue were detected. CORT-induced PC12 cell model was established. EV uptake by PC12 cells was measured and PC12 cell apoptosis was detected. The downstream targets of miR-16-5p were predicted and verified. The expressions of miR-16-5p and MYB in rats, PC12 cells, and EVs were measured. Functional rescue experiments were conducted to verify the role of miR-16-5p and MYB in PC12 cell apoptosis. RESULTS: CORT induction increased neuronal apoptosis in hippocampal tissue and induced depression-like behaviors in rats, while NSC-EV treatment improved depression-like behaviors and apoptosis in rats. In PC12 cells, NSC-EVs decreased CORT-induced PC12 cell apoptosis. NSC-EVs carried miR-16-5p into PC12 cells. miR-16-5p knockdown in EVs partially reversed the inhibitory effects of NSC-EVs on CORT-induced PC12 cell apoptosis. miR-16-5p targeted to inhibit MYB to repress CORT-induced PC12 cell apoptosis. In vivo experiments further verified that NSC-EVs reduced neuronal injury in CORT-induced depression rats via the miR-16-5p/MYB axis. CONCLUSION: NSC-EVs-mediated alleviation on neuronal injury by carrying miR-16-5p to target MYB was highly likely one of the mechanisms by which NSC-EVs mediated miR-16-5p in neuroprotection of depression rats.


Asunto(s)
Vesículas Extracelulares , MicroARNs , Células-Madre Neurales , Animales , Ratas , Corticosterona , Depresión/inducido químicamente
5.
Adv Clin Exp Med ; 33(2): 151-161, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37501511

RESUMEN

BACKGROUND: Resistance to cisplatin (DDP) in ovarian cancer therapy has been a major clinical barrier. Drug-resistant cancers have been shown to downregulate the proapoptotic protein B-cell lymphoma-2 (Bcl-2) to inhibit apoptosis. Therefore, we explored whether tasquinimod could modulate resistance to DDP through apoptotic pathways. OBJECTIVES: We aimed to explore the relationship between tasquinimod, Nur77-Bcl-2 apoptosis pathway and sensitivity of the ovarian carcinoma cell line SKOV3 and the DDP-resistant strain SKOV3/DDP cells to DDP. MATERIAL AND METHODS: First, SKOV3 and SKOV3/DDP cells were treated with 2 µg/mL DDP or 40 µM tasquinimod. Western blot and quantitative real-time polymerase chain reaction (qPCR) were then used to analyze the expression of histone deacetylase 4 (HDAC4), Nur77, Bcl-2 (BH3 domain-specific), and caspase-3. Flow cytometry, scratch-wound assay and immunofluorescence were used to detect apoptosis, migration rate, and related expression of Nur77 and Bcl-2 (BH3 domain-specific). Subsequently, 5×107 SKOV3 or SKOV3/DDP cells cultured with 2 µg/mL DDP were injected into 4-week-old female BALB/c nude mice. Then, the mice were administered 4 mg/kg DDP and 50 mg/kg tasquinimod every 3 days. Finally, the changes in tumor diameter and weight were measured. RESULTS: After treatment of SKOV3 and SKOV3/DDP cells with tasquinimod, cell migration and HDAC4 expression levels were significantly reduced, while Nur77 expression was increased. Tasquinimod treatment enhanced the expression of Nur77 and caspase-3, and cells transfected with si-Nur77 showed the opposite result. Transfection of si-Nur77 reduced the expression of caspase-3 and Nur77 in the SKOV3/DDP cells that were treated with both DDP and tasquinimod. After injection of SKOV3/DDP cells into the mice, the tumor diameter, mass and in vivo HDAC4 level were significantly decreased by tasquinimod. Meanwhile, the levels of Nur77 and Bcl-2 (BH3 domain-specific) were increased. CONCLUSIONS: Tasquinimod upregulated the Nur77/Bcl-2 pathway to induce apoptosis in SKOV3/DDP cells and enhanced the anti-tumor effect of DDP in SKOV3/DDP xenografts. Therefore, tasquinimod can be expected to find clinical applications in enhancing DDP resistance.


Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Quinolonas , Animales , Femenino , Humanos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular , Cisplatino/farmacología , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos , Ratones Desnudos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética
6.
Kidney Int ; 105(3): 524-539, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38158182

RESUMEN

The urinary tract is constantly exposed to microorganisms. Host defense mechanisms in protection from microbial colonization and development of urinary tract infections require better understanding to control kidney infection. Here we report that the lectin collectin 11 (CL-11), particularly kidney produced, has a pivotal role in host defense against uropathogen infection. CL-11 was found in mouse urine under normal and pathological conditions. Mice with global gene ablation of Colec11 had increased susceptibility to and severity of kidney and to an extent, bladder infection. Mice with kidney-specific Colec11 ablation exhibited a similar disease phenotype to that observed in global Colec11 deficient mice, indicating the importance of kidney produced CL-11 for protection against kidney and bladder infection. Conversely, intravesical or systemic administration of recombinant CL-11 reduced susceptibility to and severity of kidney and bladder infection. Mechanism analysis revealed that CL-11 can mediate several key innate defense mechanisms (agglutination, anti- adhesion, opsonophagocytosis), and limit local inflammatory responses to pathogens. Furthermore, CL-11-mediated innate defense mechanisms can act on clinically relevant microorganisms including multiple antibiotic resistant strains. CL-11 was detectable in eight of 24 urine samples from patients with urinary tract infections but not detectable in urine samples from ten healthy individuals. Thus, our findings demonstrate that CL-11 is a key factor of host defense mechanisms in kidney and bladder infection with therapeutic potential for human application.


Asunto(s)
Cistitis , Infecciones por Escherichia coli , Infecciones Urinarias , Humanos , Ratones , Animales , Vejiga Urinaria , Riñón , Colectinas/genética
7.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1006561

RESUMEN

ObjectiveThe active ingredients, action targets, and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques, and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform (TCMSP), Swiss Target Prediction, Pharmmapper, and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases, and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction (PPI). The gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group, a model group, a Cuscutae Semen group, and an estradiol valerate group, and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline, and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg-1·d-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg-1·d-1. After four weeks, samples were collected, and hematoxylin-eosin (HE) staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), Muller's tube inhibitor/anti-Muller's tube hormone (AMH), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of extracellular regulatory protein kinase (ERK), nuclear transcription factor-κB p65 (NF-κB p65), nuclear transcription factor-κB suppressor α (IκBα), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened, mainly including tumor protein p53 (TP53), protein kinase B1 (Akt1), sarcoma (SRC), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis, TNF signaling pathway, and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group, the Cuscutae Semen group can significantly upregulate AMH, E2, and HDL-C (P<0.05, P<0.01), significantly downregulate LH, TC, and LDL-C (P<0.01), greatly reduce IL-1β, IL-6, and TNF-α protein levels, as well as ERK, NF-κB p65, and their phosphorylation levels (P<0.01). ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component, multi-target, and multi-pathway approach, and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.

8.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031399

RESUMEN

Collateral vessels in cutaneous regions are the channel of qi, blood and body fluids transmission among the skin and striae and interstices, and is also the path of pathogens invasion. It is believed that the key pathogenesis of polymorphic light eruption (PLE) was toxins damaging to the skin, in which the cutaneous collaterals fail to nourish, insecurity of the muscle surface as the basis of disease, the pathogens offending qi collaterals and heat constraint to toxins as the driving factors, gradually affecting fluid collaterals and dryness-dampness coexist as the middle link, and latent pathogens in blood level and waiting for the opportunity to onset as the final stage. It is proposed that the basic treatment is to resolve toxins and tranquilize collaterals, and the internal and external treatments are combined together. The internal treatment is to resolve toxins, strengthen collaterals, and assist in unblocking the collaterals, and the modified self-prescribed Wuteng Decoction (五藤饮) plus Yigong Powder (异功散) were selected as the basic formulas, which promotes the discharge of toxin pathogens and strengthens the power of the cutaneous collaterals to protect against pathogens. For external treatment, according to the performance of skin lesions, scraping, tapping with medicinal solution, ointment were selected to drive away pathogens and resolve toxins, and soothe the cutaneous collaterals. In the early stage, the skin temperature rose with itching, tingling and no rash, scraping with the self-prescribed Yinhuangcao Clearing Oil (银黄草清解油) could be used to activate blood and regulate qi, relieve heat and resolve toxins; if the lesions showed erythema, pimples, itching, tapping with the self-prescribed Qian'ai Xunxi Formula (千艾熏洗方) could be used to diffuse qi and fluid, unblock the collaterals and clean toxins; if the skin lesions thickened with scales, the self-prescribed Yufu Ointment (愈肤膏) for external application could be used to resolve toxins and activate collaterals, moisten skin and heal up sore.

9.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031427

RESUMEN

To summarize the clinical experience of Professor AI Rudi in treating acne with triple Chinese medicinal groups combined with Chinese medicinal mask. It is believed that the pathogenesis and treatment of male and female acne are different. The key mechanism of male acne is the dysfunction of the "lung-spleen and stomach-large intestine" axis, and the method of three jiao differentiation should be used. Clinically, the triple Chinese medicinal group, Rendongteng (Lonicera japonica) - Qishe (Portulaca oleracea) - Shicangpu (Acorus gramineus), can scatter wind to relieve heat, and diffuse and disperse upper jiao; group Baihua Sheshecao (Scleromitrion diffusum) - Baixianpi (Dictamnus dasycarpus) - Tanxiang (Santalum album) can clear heat and drain dampness, and regulate middle jiao; group Huaimi (Styphnolobium japonicum) - Juemingzi (Senna tora) - Baizhu (Atractylodes macrocephala) can tonify and moisten to unblock the lower jiao. The core mechanism of female acne is the imbalance of the function of the "liver and kidney- Tiangui (reproduction-stimulating essence, corresponds with the tenth heavenly stem) - Chong and ren" axis, and the method of staged tratment based on menstrual cycle should be used. Before the menstrual period, group Tusizi (Cuscuta chinensis) - Yujing (Curcuma longa) - Qianghuoyu (Hansenia forbesii) can tonify kidney and relax liver; during the menstrual period, group Chuanxiong (Rhizoma Ligustici Chuangxiong) - Yimucao (Leonurus japonicus)- Cansha (Bombycis Faeces) can invigorate blood and regulate menstrual flow; after the menstrual period, group Huangjing (Polygonatum sibiricum) - Shanyurou (Corni Fructus) - Roucongrong (Cistanche deserticola) can nourish blood, assist yang and boost yin. Meanwhile, we attached importance to the internal and external treatment. Based on the internal administration of traditional Chinese medicine, Chinese medicinal masks were used for external application, commonly used in self-prescribed Xianglian Jinhuang Powder (香连金黄散) combined with Huoxue Powder (活血散) as the prescription for Chinese medicinal mask.

10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031496

RESUMEN

To summarize Professor AI Rudi's experience in the staged external treatment of eczema by traditional Chinese medicine (TCM). It is believed that dampness is the key pathological factor of eczema, and the treatment for dampness should be carried out throughout the whole process, with the leading idea of “three-stage treatment, dampness as the root, and treatment according to the symptoms”. The preparation and formulas of the external treatment can be applied according to the pathogenesis and lesion characteristics of each stage. In acute stage with wind-dampness and heat in the skin as the main mechanism, the treatment is to clear heat and astringe, resolve toxins and relieve itching, and the preparation is mostly solution and lotion, and the formula could be Yangzheng Xi Formula (痒症洗方), Jingfang Kushen Decoction (荆防苦参汤), Kuding Erhuang Decoction (苦丁二黄汤), and Xianglian Jinhuang Powder (香连金黄散). In subacute stage with phlegm-dampness and heat as the main mechanism, the treatment is to remove dampness and turbidity, clean up the residual heat; the preparation is mostly ointment, and the formula include Shehuang Ointment (蛇黄软膏), Huanglian Ointment (黄连膏), and Zihuan Diding Ointment (紫花地丁软膏). In chronic stage with phlegm-dampness stagnation as the main mechanism, the treatment is to remove dampness and eliminate phlegm, remove blood stasis and stop itching, and the formula could be Zhiyang soft Ointment (止痒软膏), Runji Ointment (润肌膏), Yufu Ointment (愈肤膏); jojoba oil and olive oil are often used as external moisturiser for daily care.

11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031520

RESUMEN

The membranous tube of sanjiao (三焦) is not only the path of the transport of fluid and qi, but the way of the invasion of pathogenic factors, therefore, it cooperates with the skin mucous membrane physically and influence on each other pathologically. It is believed that the core pathogenesis of chronic urticaria is pathogens intruding sanjiao, membrane collaterals acute spasm, and fluid and qi disturbance, of which defense qi insufficiency and pathogens intruding sanjiao initiates the disease, while struggle between healthy and pathogenic qi and membrane collaterals acute spasm is the intermediate stage, and disturbed fluid, qi and blood movement is the terminal stage. Following the core treatment principle of dredging sanjiao, the internal treatment is to open striae and interstices and dispel pathogens out using self-made Guben Shufeng Decoction(固本疏风汤)modifications, and the external treatment is to dredge and regulate membrane collaterals, move qi and fluid, and treat sanjiao simultaneously, commonly using cutting therapy on Danzhong (RN 17) to move qi and fluid, seal umbilical therapy on Shenque (RN 8) to supplement and nourish ying-wei (营卫), and natural moxibustion on Xuehai (SP 10) to move blood and unblock collaterals.

12.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031544

RESUMEN

This article summarized the clinical experience of Professor AI Rudi in staged treatment according to pattern differentiation of systemic lupus erythematosus (SLE). It is believed that SLE is characterized by kidney yin deficiency and heat toxin obstruction as the core disease mechanism. The staged treatment principle is to nourish yin and clear heat, invigorate blood and resolve toxins. In the early stage of heat toxins accumulation, the focus is on treating the branch and strengthen the kidneys as early as possible, recommending self-designed Liangxue Xiaofeng Powder (凉血消风散) with modifications. In the middle stage, there is yin deficiency with internal heat, which requires nourishing kidney yin and eliminating pathogenic factors. The prescription suggested is self-designed Shouwu Dihuang Decoction (首乌地黄汤). In the late stage, there is yin impairment affecting yang, which requires a gradual consolidation of the foundation and harmonization of yin and yang, usually with Zhenwu Decoction (真武汤) and Zishen Tongguan Powder (滋肾通关散) with modifications. At the same time, the treatment emphasizes the integration of Chinese and Western medicine, and use of self-designed Ershen Dihuang Pill (二参地黄丸) after initial remission to consolidate the effect and prevent relapse. External treatment should also be given importance to, and Hongyou Ointment (红油膏) can be used to treat SLE skin lesions, reduce swelling, and relieve pain.

13.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031867

RESUMEN

ObjectiveTo observe the effect of Youguiwan on the leptin/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in the lung tissue of the rat model of chronic obstructive pulmonary disease (COPD) due to kidney-Yang deficiency. MethodForty rats were modeled for COPD with the syndrome of kidney-Yang deficiency by intratracheal instillation of lipopolysaccharide on day 1 and day 14 and continuous fumigation for 6 weeks, during which hydrocortisone was injected intramuscularly at an interval of 3 days. The modeled rats were randomized into model, high- (11.7 g·kg-1), medium- (5.85 g·kg-1), and low-dose (2.93 g·kg-1) Youguiwan, and aminophylline (0.054 g·kg-1) group. In addition, 8 SD rats were set as the blank group. After the completion of modeling, the rats in each group were administrated with the corresponding drug by gavage for 28 consecutive days. After the last administration, samples were collected. A lung function analyzer was used to evaluate the lung function of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-17A (IL-17A), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the bronchoalveolar lavage fluid (BALF). Hematoxylin-eosin staining was employed to observe the pathological changes in the lung tissue, and Masson staining was employed to observe the deposition of blue collagen fibers around bronchi in the lung tissue and calculate the inflammation score. The immunofluorescence assay was employed to measure the protein content of collagen type Ⅰ (ColⅠ) and α-smooth muscle actin (α-SMA) in the bronchi. The protein and mRNA levels of leptin, IL-17A, JAK2, and STAT3 in the lung tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction, respectively. ResultCompared with the blank group, the model group showed decreased lung function (P<0.01), elevated levels of IL-6, IL-17A, and TNF-α in the BALF (P<0.01), and increased lung inflammation score, deposition of subcutaneous collagen fibers in the airway, and ColⅠ and α-SMA proteins (P<0.01). Furthermore, the modeling up-regulated the proteins and mRNA levels of leptin, IL-17A, JAK2, and STAT3 in the lung tissue (P<0.01) and enhanced the phosphorylation of JAK2 and STAT3 (P<0.01). Compared with the model group, high- and medium-dose Youguiwan improved the lung function, decreased the inflammation score, reduced collagen fiber deposition and ColⅠ and α-SMA proteins, lowered the levels of IL-6, IL-17A, and TNF-α in the BALF, down-regulated the mRNA and protein levels of leptin, JAK2, STAT3, and IL-17A, and weakened the phosphorylation of JAK2 and STAT3 (P<0.05, P<0.01). The aminophylline group had higher IL-17A and TNF-α levels than the high-dose Youguiwan group, lower IL-17A level than the medium and low-dose Youguiwan groups, and lower TNF-α level than the low-dose Youguiwan group. Compared with the aminophylline group, the high- and medium-dose Youguiwan groups showed reduced deposition of collagen fibers and protein levels of ColⅠ and α-SMA around the bronchi in the lung tissue (P<0.05, P<0.01), decreased inflammation score, and down-regulated protein and mRNA levels of leptin, JAK2, STAT3, and IL-17A in the lung tissue. ConclusionYouguiwan can prevent airway remodeling by inhibiting IL-17A to reduce inflammation and collagen deposition in COPD rats, which may be related to the inhibition of the leptin/JAK2/STAT3 signaling pathway.

14.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1039625

RESUMEN

ObjectiveTo investigate the effect of Zuoguiwan on the ovarian function in the rat model of cyclophosphamide-induced premature ovarian failure (POF) based on the changes of ferroptosis pathway. MethodForty SD rats were randomized into blank, model, and low- and high-dose (2, 8 g·kg-1, respectively) Zuoguiwan groups, with 10 rats in each group. The rats in the other groups except the normal group were intraperitoneally injected with CTX at a dose of 50 mg·kg-1 on the first day and 8 mg·kg-1 from the second day to the fifteenth day for the modeling of POF. After modeling, the rats were administrated with corresponding drugs or normal saline by gavage for four weeks. Hematoxylin-eosin staining was performed to observe the pathological changes in the ovarian tissue. The mitochondria of the ovarian tissue was observed by electron microscopy. The serum levels of follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), anti-Mullerian hormone (AMH), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and iron ion were measured by biochemical methods and enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain (FTH1), and acyl-CoA synthetase long chain family member 4 (ACSL4). ResultCompared with the blank group, the model group showcased significantly increased atretic follicles, atrophied, fragmented, and vacuolated mitochondria, and reduced, loose, and disordered cristae in mitochondria. Compared with the model group, high-dose Zuoguiwan increased mature follicles, the volume of mitochondria in the ovary, alleviated the vacuolation, and improved the number and arrangement of mitochondrial cristae. Compared with the blank group, the modeling elevated the levels of iron, MDA, FSH, and LH, up-regulated the expression of GPX4, SLC7A11, and FTH1 (P<0.05, P<0.01), decreased the activities of SOD and CAT, lowered the levels of E2 and AMH, and down-regulated the expression of ACSL4 (P<0.05, P<0.01). Compared with the model group, drug interventions lowered the levels of iron, MDA, FSH, and LH, down-regulated the expression of GPX4, SLC7A11, and FTH1 (P<0.05, P<0.01), increased the activity of CAT, elevated the levels of E2 and AMH, and up-regulated the expression of ACSL4 (P<0.05, P<0.01). ConclusionZuoguiwan may inhibit the occurrence of ferroptosis by regulating the SLC7A11/GPX4 axis, thereby improving the ovarian function of POF rats.

15.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1039626

RESUMEN

ObjectiveTo observe the effect of Zuoguiwan on ovarian reserve in the female offspring rat model of prenatal stress (PS) and explore the mechanism based on Toll-like receptor 4/nuclear factor-κB p65 (TLR4/NF-κB p65) signaling pathway. MethodThirty-two pregnant rats were prepared and randomized into four groups (n=8): control, model, Zuoguiwan (18.9 mg·kg-1), and vitamin E (1.44 mg·kg-1). Except the control group, the other three groups were subjected to chronic unpredictable mild stress (CUMS) from day 11 of pregnancy, and the modeling was accompanied by gavage with corresponding drugs until delivery. The PS model was evaluated by the sucrose preference test, open field test, and serum corticosterone (CORT) level. The estrous cycle was monitored and the morphological changes in the ovarian tissue were observed. The serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Mullerian hormone (AMH) in the 75-day-old offspring rats were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the ovarian reserve. The ovary and uterus indices were calculated. The serum levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The morphology of the ovarian tissue in the offspring on the day of birth and day 75 after birth was observed by hematoxylin-eosin staining. The transport of NF-κB p65 to the nucleus in the ovaries of the 75-day-old offspring was detected by the immunofluorescence (IF) assay. The expression of TLR4, NF-κB p65 and other related proteins in the ovarian tissue was determined by Western blot. ResultCompared with the control group, the model group showed reduced primordial follicles in the offspring on the day of birth (P<0.01) as well as disturbed estrous cycle, decreased ovary index and uterus index (P<0.01), reduced corpus luteum, increased atretic follicles (P<0.01), lowered serum levels of AMH and E2 (P<0.01), elevated serum levels of LH, FSH, IL-1β, and TNF-α (P<0.05, P<0.01), and up-regulated protein levels of TLR4, NF-κB p65, recombinant myeloid differentiation factor 88 (MyD88), and phosphorylated NF-κB inhibitor (p-IκBα) (P<0.01) in the 75-day-old offspring rats. Compared with the model group, Zuoguiwan and vitamin E increased the primordial follicles in the offspring on the day of birth (P<0.01). Moreover, they resumed the estrous cycle, increased the ovary and uterine indices (P<0.05, P<0.01) and corpus luteum (P<0.01), reduced atretic follicles (P<0.01), elevated the serum levels of AMH and E2 (P<0.05, P<0.01), lowered the serum levels of LH, FSH, IL-1β, and TNF-α (P<0.05, P<0.01), and down-regulated the expression of TLR4, NF-κB p65, MyD88, and p-IκB-α (P<0.05, P<0.01) in the 75-day-old offspring. ConclusionZuoguiwan can improve the ovarian reserve in the offspring rat model of congenital kidney deficiency by regulating the TLR4/NF-κB p65 signaling pathway.

16.
Chinese Journal of School Health ; (12): 375-378, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013525

RESUMEN

Objective@#The study aims to explore the neural mechanism of cognitive differences in college students with posttraumatic stress disorder under verbal fluency task based on functional near infrared spectroscopy (fNIRS), so as to provide neuroimaging support for the evaluation, diagnosis and treatment of posttraumatic stress disorder(PTSD).@*Methods@#Posttaumatic Stress Disorder Checklist Combat(PCL-C) was used to screen the subjects, including 21 students in PTSD group (PCL-C≥38) and 30 students in control group from September to Novenber in 2020. A 53 channel near infrared spectroscopy device was used to collect cerebral blood oxygen signals under the verbal fluency task, and correlation analysis, Mann Whitney U test and independent sample t test were performed on the results.@*Results@#The difference in the total average score of PCL-C Scale between PTSD group and the control group(46.38±6.96,25.57±6.09) was statistically significant ( t=11.33, P <0.05). Correlation analysis showed that Avg-HbO in left dorsolateral prefrontal lobe was negatively correlated with PCL-C Score ( r=-0.37, P <0.05). Mann Whitney U test showed that in the left dorsolateral prefrontal lobe (Ch6), the Avg-HbO change in PTSD group [0.19(-0.09, 0.86)mmol/(L〖KG*7〗·mm)] was significantly lower than the control group [0.79( 0.37 , 1.47)mmol/(L ·mm)] ( Z=2.16, P <0.05), which was statistically significant.@*Conclusions@#The degree of PTSD was negatively correlated with the index of oxygenated hemoglobin in the left dorsolateral prefrontal lobe, and the oxygenated hemoglobin content in the PTSD group was lower than that in the normal group. In the future, fNIRS may be used to collect blood oxygen signals from the left dorsolateral prefrontal lobe in cognitive tasks to provide imaging evidence for the identification of PTSD.

17.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1016458

RESUMEN

ObjectiveTo study the effects of Epimedii Folium polysaccharides on mice with exercise-induced fatigue and explore its possible mechanism of action. MethodICR male mice screened by swimming training were randomly divided into a control group, model group, vitamin C group, and low, medium, and high dose groups of Epimedii Folium polysaccharides, with eight mice in each group. The exercise-induced fatigue model was established by weight-bearing swimming training in each group except for the control group. After two weeks of weight-bearing swimming, the Epimedii Folium polysaccharide groups were given 100, 200, 400 mg∙kg-1 of Epimedii Folium polysaccharides by gavage, and the vitamin C group was given 200 mg∙kg-1 of vitamin C by gavage. The control group and the model group were given equal amounts of saline for 14 d. At the end of the experimental period, the body mass of the mice in each group and the time of last swimming due to exhaustion were recorded. Serum urea nitrogen (BUN), lactic acid (LA), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidation (GSH-Px), myoglycogen (MG) in skeletal muscle, hepatic glycogen (HG) in the liver were detected by kits. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in muscle tissue. Western blot was used to detect the protein expression of p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation (p)-p38 MAPK, extracellular signal-regulated kinase1/2 (ERK1/2), nuclear factor-κB (NF-κB), p-NF-κB, interleukin-1β (IL-1β), and interleukin-6 (IL-6) in muscle tissue. The immunofluorescence (IF) method was used to detect the expression of tumor necrosis factor-α (TNF-α) in skeletal muscle tissue of mice in each group. ResultCompared with the control group, the body mass of mice in the model group decreased, and the time of last swimming due to exhaustion decreased (P<0.01). In addition, there were significantly higher serum levels of the fatigue metabolites LA, LDH, BUN, and lipid peroxidation product MDA (P<0.01) and decreased levels of MG, HG, SOD, and GSH-Px (P<0.01). The protein expressions of p-p38 MAPK, ERK1/2, p-NF-κB, IL-1β, IL-6, and TNF-α in skeletal muscle tissue were significantly higher than those of the control group (P<0.01). Compared with the model group, the body mass and time of last swimming due to exhaustion of the mice in the low, medium, and high dose groups of Epimedii Folium polysaccharides and the vitamin C group were increased (P<0.05, P<0.01), and the contents of LA, LDH, BUN, and MDA were significantly decreased (P<0.05, P<0.01). The levels of MG, HG, SOD, and GSH-Px increased (P<0.05, P<0.01), and the protein expression levels of p-p38 MAPK, ERK, p-NF-κB, IL-1β, IL-6, and TNF-α in skeletal muscle tissue decreased (P<0.05, P<0.01). ConclusionEpimedii Folium polysaccharides can play a role in alleviating exercise-induced fatigue by inhibiting the p38 MARK/NF-κB signaling pathway, thereby reducing the accumulation of metabolites, improving the activity of antioxidant enzymes, increasing the glycogen content of the body, and reducing inflammation in skeletal muscle.

18.
Artículo en Inglés | MEDLINE | ID: mdl-38021364

RESUMEN

Background: The endoscopic nasojejunal (NJ) placement plays a pivotal role in the nutritional support of critically ill patients. However, the conventional endoscopy-guided tube insertion method presents issues of excessive procedural duration. We have enhanced the traditional endoscopy-guided catheter placement method, enabling a faster and more convenient catheter insertion. Methods: We improved the traditional endoscopically guided technique by incorporating an extra silk thread knot at the 25 cm mark on the jejunal segment of the NJ tube to assist endoscopists in accurate tube placement. We conducted the improved NJ tube placement on critically ill patients in need of enteral nutrition (EN). Laboratory data were retrospectively collected before and after the 7-day period of NJ tube placement and EN treatment to evaluate the effectiveness and safety of the improved method. Results: A total of 88 critically ill patients, with an average age of 59.6±15.5 years, and a male ratio of 86.4%, who underwent the improved NJ tube placement method were enrolled into analysis finally, achieving a 100% success rate of NJ tube insertion. The average time for tube insertion was 5.9±2.2 min, with a mean insertion depth of 108.8±12.5 cm. The EN tolerance score was 0.79±0.98. Following 7 days of EN therapy, the patients showed significant improvement in serum albumin levels compared to baseline (36.42 vs. 33.66 g/L, P<0.001). Conclusions: The improved endoscopically guided NJ tube placement technique is a rapid and safe procedure with excellent patient tolerance. It significantly improves the nutritional status of critically ill patients and facilitates the administration of EN, which requires further validation through randomized controlled trials.

19.
Eur J Neurosci ; 58(4): 2961-2984, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37518943

RESUMEN

Post-stroke depression, a common complication after stroke, severely affects the recovery and quality of life of patients with stroke. Owing to its complex mechanisms, post-stroke depression treatment remains highly challenging. Hippocampal synaptic plasticity is one of the key factors leading to post-stroke depression; however, the precise molecular mechanisms remain unclear. Numerous studies have found that neurotrophic factors, protein kinases and neurotransmitters influence depressive behaviour by modulating hippocampal synaptic plasticity. This review further elaborates on the role of hippocampal synaptic plasticity in post-stroke depression by summarizing recent research and analysing possible molecular mechanisms. Evidence for the correlation between hippocampal mechanisms and post-stroke depression helps to better understand the pathological process of post-stroke depression and improve its treatment.


Asunto(s)
Depresión , Calidad de Vida , Humanos , Depresión/etiología , Plasticidad Neuronal/fisiología , Hipocampo/metabolismo , Factores de Crecimiento Nervioso/metabolismo
20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(1): 149-154, 2023 Feb.
Artículo en Chino | MEDLINE | ID: mdl-36861169

RESUMEN

Acute coronary syndrome (ACS),with increasing mortality year by year,has become a major public health problem in China.Exercise rehabilitation as an important part of the out-of-hospital rehabilitation for the patients with heart diseases can further reduce the mortality of patients on the basis of drug treatment.The available studies have proved that high-intensity interval training (HIIT) is more effective and efficient than moderate-intensity continuous training (MICT) such as walking and jogging on chronic cardiovascular diseases such as heart failure,stable coronary heart disease,and hypertension and has high security.According to the latest research,HIIT can reduce the platelet response,mitigate myocardial ischemia-reperfusion injury,and increase the exercise compliance of ACS patients more significantly than MICT.Moreover,it does not increase the risk of thrombotic adverse events or malignant arrhythmia.Therefore,HIIT is expected to become an important part of exercise prescription in out-of-hospital cardiac rehabilitation strategy for the patients with ACS.


Asunto(s)
Síndrome Coronario Agudo , Rehabilitación Cardiaca , Insuficiencia Cardíaca , Entrenamiento de Intervalos de Alta Intensidad , Humanos , Plaquetas
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