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1.
Phytomedicine ; 128: 155432, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38518645

RESUMEN

BACKGROUND: Cancer, the second leading cause of death worldwide following cardiovascular diseases, presents a formidable challenge in clinical settings due to the extensive toxic side effects associated with primary chemotherapy drugs employed for cancer treatment. Furthermore, the emergence of drug resistance against specific chemotherapeutic agents has further complicated the situation. Consequently, there exists an urgent imperative to investigate novel anticancer drugs. Steroidal saponins, a class of natural compounds, have demonstrated notable antitumor efficacy. Nonetheless, their translation into clinical applications has remained unrealized thus far. In light of this, we conducted a comprehensive systematic review elucidating the antitumor activity, underlying mechanisms, and inherent limitations of steroidal saponins. Additionally, we propose a series of strategic approaches and recommendations to augment the antitumor potential of steroidal saponin compounds, thereby offering prospective insights for their eventual clinical implementation. PURPOSE: This review summarizes steroidal saponins' antitumor activity, mechanisms, and limitations. METHODS: The data included in this review are sourced from authoritative databases such as PubMed, Web of Science, ScienceDirect, and others. RESULTS: A comprehensive summary of over 40 steroidal saponin compounds with proven antitumor activity, including their applicable tumor types and structural characteristics, has been compiled. These steroidal saponins can be primarily classified into five categories: spirostanol, isospirostanol, furostanol, steroidal alkaloids, and cholestanol. The isospirostanol and cholestanol saponins are found to have more potent antitumor activity. The primary antitumor mechanisms of these saponins include tumor cell apoptosis, autophagy induction, inhibition of tumor migration, overcoming drug resistance, and cell cycle arrest. However, steroidal saponins have limitations, such as higher cytotoxicity and lower bioavailability. Furthermore, strategies to address these drawbacks have been proposed. CONCLUSION: In summary, isospirostanol and cholestanol steroidal saponins demonstrate notable antitumor activity and different structural categories of steroidal saponins exhibit variations in their antitumor signaling pathways. However, the clinical application of steroidal saponins in cancer treatment still faces limitations, and further research and development are necessary to advance their potential in tumor therapy.


Asunto(s)
Antineoplásicos Fitogénicos , Saponinas , Esteroides , Saponinas/farmacología , Saponinas/química , Saponinas/uso terapéutico , Humanos , Esteroides/farmacología , Esteroides/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Neoplasias/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos
2.
Cancer Res ; 84(6): 855-871, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38486485

RESUMEN

Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain refractory to ICIs, and druggable targets for upregulating MHC-I are limited. Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Mechanistically, FASN inhibition reduced palmitoylation of MHC-I that led to its lysosomal degradation. The palmitoyltransferase DHHC3 directly bound MHC-I and negatively regulated MHC-I protein levels. In an orthotopic HCC mouse model, Fasn deficiency enhanced MHC-I levels and promoted cancer cell killing by tumor-infiltrating CD8+ T cells. Moreover, the combination of two different FASN inhibitors, orlistat and TVB-2640, with anti-PD-L1 antibody robustly suppressed tumor growth in vivo. Multiplex IHC of human HCC samples and bioinformatic analysis of The Cancer Genome Atlas data further illustrated that lower expression of FASN was correlated with a higher percentage of cytotoxic CD8+ T cells. The identification of FASN as a negative regulator of MHC-I provides the rationale for combining FASN inhibitors and immunotherapy for treating HCC. SIGNIFICANCE: Inhibition of FASN increases MHC-I protein levels by suppressing its palmitoylation and lysosomal degradation, which stimulates immune activity against hepatocellular carcinoma and enhances the efficacy of immune checkpoint inhibition.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Humanos , Ratones , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular , Acido Graso Sintasa Tipo I , Neoplasias Hepáticas/genética , Proteínas
3.
Heliyon ; 10(4): e26145, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38390090

RESUMEN

Underwater light attenuation leads to decreased image contrast. This reduction in contrast subsequently decreases target visibility. Additionally, marine target detection is challenging due to multi-scale problems from varying target-to-device distances, complex target clustering, and noise from waterborne particulates.To address these issues, we propose MTD-YOLOv5.Initially, we enhance image contrast with grayscale equalization and mitigate color shift issues through color space transformation.We then introduce a novel feature extraction module, PCBR, combining max pooling and convolution layers for more effective target feature extraction from the background.Furthermore, we present the Multi-Scale Perceptual Hybrid Pooling (MHP) module.This module integrates horizontal and vertical receptive fields to establish long-range dependencies, thereby capturing hidden target information in deep network feature maps. In the Labeled Fishes in the Wild test datasets, MTD-YOLOv5 achieves a precision of 88.1% and a mean Average Precision (mAP[0.5:.95]) of 49.6%.These results represent improvements of 2.6% in precision and 0.4% in mAP over the original YOLOv5.

4.
Sci Total Environ ; 912: 169321, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38103607

RESUMEN

Epiphytic and superficial sediment biofilm-dwelling microbial communities play a pivotal role in water quality regulation and biogeochemical cycling in shallow lakes. However, the interactions are far from clear between water physicochemical parameters and microbial community on aquatic plants and in surface sediments of lake in trophic agriculture area. This study employed Illumina sequencing, Partial Least Squares Path Modeling (PLS-PM), and physico-chemical analytical methods to explore the interactions between water quality and microbes (bacteria and eukaryotes) in three substrates of trophic shallow Lake Cyohoha North, Rwanda. The Lake Cyohoha was significantly polluted with total phosphorus (TP), total nitrogen (TN), nitrate nitrogen (NO3-N), and ammonia nitrogen (NH3-N) in the wet season compared to the dry season. PLS-PM revealed a strong positive correlation (+0.9301) between land use types and physico-chemical variables in the rainy season. In three substrates of the trophic lake, Proteobacteria, Cyanobacteria, Firmicutes, and Actinobacteria were dominant phyla in the bacterial communities, and Rotifers, Platyhelminthes, Gastrotricha, and Ascomycota dominated in microeukaryotic communities. As revealed by null and neutral models, stochastic processes predominantly governed the assembly of bacterial and microeukaryotic communities in biofilms and surface sediments. Network analysis revealed that the microbial interconnections in Ceratophyllum demersum were more stable and complex compared to those in Eichhornia crassipes and sediments. Co-occurrence network analysis (|r| > 0.7, p < 0.05) revealed that there were complex interactions among physicochemical parameters and microbes in epiphytic and sediment biofilms, and many keystone microbes on three substrates played important role in nutrients removal, food web and microbial community stable. These findings emphasize that eutrophic water influence the structure, composition, and interactions of microbes in epiphytic and surface sediment biofilms, and provided new insights into the interconnections between water quality and microbial community in presentative substrates in tropical lacustrine ecosystems in agriculturally polluted areas. The study provides useful information for water quality protection and aquatic plants restoration for policy making and catchment management.


Asunto(s)
Cianobacterias , Microbiota , Lagos/microbiología , Calidad del Agua , Biopelículas , Nitrógeno , Sedimentos Geológicos/microbiología , China
5.
Plant Phenomics ; 5: 0098, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37791248

RESUMEN

Plant phenomics aims to perform high-throughput, rapid, and accurate measurement of plant traits, facilitating the identification of desirable traits and optimal genotypes for crop breeding. Salvia miltiorrhiza (Danshen) roots possess remarkable therapeutic effect on cardiovascular diseases, with huge market demands. Although great advances have been made in metabolic studies of the bioactive metabolites, investigation for S. miltiorrhiza roots on other physiological aspects is poor. Here, we developed a framework that utilizes image feature extraction software for in-depth phenotyping of S. miltiorrhiza roots. By employing multiple software programs, S. miltiorrhiza roots were described from 3 aspects: agronomic traits, anatomy traits, and root system architecture. Through K-means clustering based on the diameter ranges of each root branch, all roots were categorized into 3 groups, with primary root-associated key traits. As a proof of concept, we examined the phenotypic components in a series of randomly collected S. miltiorrhiza roots, demonstrating that the total surface of root was the best parameter for the biomass prediction with high linear regression correlation (R2 = 0.8312), which was sufficient for subsequently estimating the production of bioactive metabolites without content determination. This study provides an important approach for further grading of medicinal materials and breeding practices.

6.
MethodsX ; 11: 102423, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37846353

RESUMEN

To extend the network life, an ordinal potential game is introduced into network topology control, and a network topology control algorithm based on the Theil entropy measure is designed by improving the revenue function. The revenue function is based on the Theil entropy measure, whose factors are in the residual energy of the nodes and their neighbors. By using a primary payoff function that considers all initial network factors and a secondary one that addresses connectivity in case of reduced residual energy, a segmentation function can calculate the model's payoff. Simulation experiments show that compared to the existing game algorithms of 3DK-RNG, DEBA, and EFPC, the proposed algorithm can effectively eliminate redundant links, reduce node degree and network link length, balance node energy consumption, enhance network load, and extend the network life cycle.•A Network Topology Control Algorithm Based on the Fusion of Thiel Entropy and Ordinal Potential Games.•A network topology control method for extending the network lifecycle is successfully established.•It proposes that the performance of the fusion topology control algorithm is significantly superior to other single algorithms in the paper.

7.
J Gastrointestin Liver Dis ; 32(2): 139, 2023 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-37345591

RESUMEN

This report showed the clinical manifestations of a 26-year-old patient who was admitted to our hospital with epigastric discomfort. Computed tomography (CT) showed a hyper-density linear object Esophagogastroduodenoscopy (EGD) revealed a submucosal bulge in the gastric antrum. And endoscopic ultrasonography (EUS) demonstrated a hyperechoic lesion with a posterior shadowing in the anechoic area. Based on the above results, a diagnosis of fishbone invasion into the antral submucosa was considered. Then endoscopic submucosal dissection (ESD) was performed and a 3-cm-long fishbone was extracted with the forceps. As a rare case, the imaging findings of the fishbone under the endoscopy and the computed tomography were described.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Humanos , Adulto , Antro Pilórico/diagnóstico por imagen , Antro Pilórico/cirugía , Neoplasias Gástricas/patología , Endosonografía , Endoscopía Gastrointestinal , Resección Endoscópica de la Mucosa/métodos
8.
Org Biomol Chem ; 21(16): 3355-3359, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37038891

RESUMEN

A simple and novel Pd-catalysed cross-coupling reaction of allenylic carbonates with different gem-diborylalkanes was developed. Under mild reaction conditions, synthetically useful and versatile isoprenylboronates could be obtained selectively in moderate to high yields. Furthermore, the utility of the novel isoprenylboronate is demonstrated through isoprenylboration and homologation.

9.
Chin Herb Med ; 15(1): 57-62, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36875427

RESUMEN

Objective: The content of saikosaponins in genus Bupleurum is increased with numbers of lateral root, but the genetic mechanisms are largely unknown. This study aims to identify the heme oxygenase (HO) gene family members of B. chinense and B. scorzonerifolium, and assess their role in the root development in Bupleurum. Methods: The gene sequences of HO family were selected from iso-seq full-length transcriptome data of B. chinense and B. scorzonerifolium, and were analyzed in physicochemical properties, conserved domains, motifs and phylogenetic relationship. In addition, the expression patterns of HO gene in different parts of roots were compared via transcriptome sequencing and qRT-PCR in the two species. Results: Five Bupleurum HO genes (BcHO1-BcHO5) belonging to the HO1 subfamily were identified from the transcriptome data, whereas the HO2 subfamily member was not identified. The expression levels of BcHO1 and BcHO2 were significantly higher than those of other three HO members in the transcriptome analysis. In addition, the expression profile of BcHO1 showed consistency with lateral root development in B. chinense and B. scorzonerifolium. Conclusion: Hos might participate in the auxin-induced morphogenesis of lateral roots. The yield of saikosaponin may be improved by manipulating expression of these genes.

10.
Pharm Biol ; 61(1): 288-297, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36815239

RESUMEN

CONTEXT: Fibroblast senescence was reported to contribute to the pathological development of idiopathic pulmonary fibrosis (IPF), and baicalein is reported to attenuate IPF. OBJECTIVE: This study explores whether baicalein attenuates lung fibrosis by regulating lung fibroblast senescence. MATERIALS AND METHODS: Institute of Cancer Research (ICR) mice were randomly assigned to control, bleomycin (BLM), baicalein and BLM + baicalein groups. Lung fibrosis was established by a single intratracheal dose of BLM (3 mg/kg). The baicalein group received baicalein orally (100 mg/kg/day). Sirtuin 3 (Sirt3) siRNA (50 µg) was injected through the tail vein once a week for 2 weeks to explore its effect on the anti-pulmonary fibrosis of baicalein. RESULTS: BLM-treated mice exhibited obvious lung fibrosis and fibroblast senescence by showing increased levels of collagen deposition (27.29% vs. 4.14%), hydroxyproline (208.05 vs. 40.16 ng/mg), collagen I (25.18 vs. 9.15 µg/mg), p53, p21, p16, MCP-1, PAI-1, TNF-α, MMP-10 and MMP-12 in lung tissues, which were attenuated by baicalein. Baicalein also mitigated BLM-mediated activation of TGF-ß1/Smad signalling pathway. Baicalein restored the BLM-induced downregulation of Sirt3 expression in lung tissues and silencing of Sirt3 abolished the inhibitory role of baicalein against BLM-induced lung fibrosis, fibroblast senescence and activation of TGF-ß1/Smad signalling pathway. CONCLUSIONS: Baicalein preserved the BLM-induced downregulation of lung Sirt3 expression, and thus the suppression of TGF-ß1/Smad signalling pathway and lung fibrosis, which might provide an experimental basis for treatment of IPF.


Asunto(s)
Fibrosis Pulmonar , Sirtuina 3 , Ratones , Animales , Fibrosis Pulmonar/patología , Bleomicina/efectos adversos , Factor de Crecimiento Transformador beta1/metabolismo , Sirtuina 3/metabolismo , Sirtuina 3/farmacología , Sirtuina 3/uso terapéutico , Pulmón , Fibroblastos , Colágeno/metabolismo
11.
Plant Biotechnol Rep ; 17(2): 159-169, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35873882

RESUMEN

Bupleurum chinense DC is an important medicinal plant with many active ingredients that are used for the treatment of different types of diseases and valued in pharmaceutical markets. In vitro shoot regeneration can efficiently contribute to the improvement of B. chinense. In the present study, we investigated the effects of the explant type and plant growth regulators (PGRs) on embryogenic callus induction and plant regeneration in B. chinense. Our investigation demonstrated that 2 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) combined with 1 mg/L thidiazuron (TDZ) played a major role in promoting callus induction from leaf, hypocotyl and stem 2 explants, whereas the most effective treatment for stem 1 callus formation was Murashige and Skoog (MS) medium supplemented with 1 mg/L 2,4-D, 0.5 mg/L 6-benzyladenine (BA) and 0.5 mg/L kinetin (Kin). The highest shoot regeneration rate (57.14%) was obtained from hypocotyl-induced calli in MS medium with 0.5 mg/L Kin after 12 weeks of cultivation. This regeneration protocol can be used in large-scale cultivation and may be useful for future genetic modifications of B. chinense .

12.
Acta Pharmaceutica Sinica ; (12): 2468-2475, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-999138

RESUMEN

Dengzhan Shengmai capsule, as a compound Chinese patent medicine, consists of four herbs: Herba Erigerontis, Ginseng, Ophiopogon, and Schisandrae Chinensis Fructus, and contains significant components of flavonoids, lignans, saponins, and organic acids. It is widely used clinically to treat cerebrovascular diseases such as chronic cerebral hypoperfusion and dementia with remarkable efficacy. This study proposes a research strategy for multi-component traditional Chinese medicine metabolites based on prediction databases and unfolds the analysis using Dengzhan Shengmai capsule as an example. Using the UPLC-Q-TOF/MS method, the analytical method was established and detected biological samples such as urine, feces, and bile of rats before and after administration based on the prediction of theoretical metabolites of Dengzhan Shengmai capsule. The possible secondary fragment ion information of metabolites was identified by comparing the detected results with prediction databases. The metabolites were identified based on the archetypal component mass spectrometric cleavage law and multistage mass spectrometric data. 51 metabolites, mainly flavonoid, organic acid, and lignan constituents, were finally identified from rat biosamples based on 306 theoretical metabolites of Dengzhan Shengmai capsule. This study provides a new strategy for the identification of metabolites in vivo and the analysis of metabolic pathways of TCM. The study complied with the procedures established by the Animal Experiment Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethics examine (No. 00003645).

13.
Chinese Pharmacological Bulletin ; (12): 807-811, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013798

RESUMEN

Rutin is extracted from Ruta graveolens L. with many pharmacological activities such as anti-inflammation, anti-oxidation , protecting cardiovascular system and analgesia. As a natural product, rutin has the advantages of low side effects and difficult tolerance, but its instability and low bioavailability still limit its clinical application. This paper summarizes the analgesic mechnism of rutin, and looks forward to the clinical applica¬tion of rutin based on its derivative and dosage forms. It is expected to provide ideas for further analgesic research and drug development and application of rutin in the future.

14.
Chinese Pharmacological Bulletin ; (12): 2338-2345, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013680

RESUMEN

Aim To observe the effect of corticotropin-releasing factor ( CRF) -expressing neurons on presympathetic neurons in hypothalamic paraventricular nucleus ( PVN) of normotensive Wistar Kyoto ( WKY) rats or spontaneously hypertensive rats (SHR) , and to elucidate the underlying neuronal circuit mechanism of central sympathetic hyperexcitability. Methods The expression levels of CRF protein in WKY rats and SHR PVN were determined by Western blot. Meanwhile, the WKY and SHR PVN CRF-expressing neurons and presympathetic neurons were observed by immunofluo-rescent staining. Adult WKY rats and SHR were used in this study. By microinjection of Cre-dependent ade-no-associated viruses ( AAV) that specifically recognized the CRF promoter and AAV of chemogenetics into the PVN, CRF-expressing neurons expressed designer receptors exclusively activated by designer drugs (DREADDs). Human M3 muscarinic DREADD coupled to Gq receptor ( hM3 Dq) was specifically expressed in PVN CRF-expressing neurons in WKY rats, while human M4 muscarinic DREADD coupled to Gi receptor ( hM4Di) was specifically expressed in PVN CRF-expressing neurons in SHR. Clozapine-N-oxide (CNO) , as a designer ligand, would couple to excitatory hM3Dq or inhibitory hM4Di to regulate the excitability of PVN CRF-expressing neurons. Then the PVN presympathetic neurons were retrogradely labeled by microinjection of fluosecent tracer into the intermedio-lateral column (IML) of spinal cord. Lastly, whole cell patch clamp was used to determine the effect of CNO (10 jjumol L~ ) on spontaneous excitatory postsynaptic currents ( sEPSCs) and current-evoked firing of PVN presympathtic neurons of WKY rats and SHR. Results The expression of CRF protein in the PVN of SHR was significantly higher than that of WKY rats, and the activity and number of CRF-expressing neurons in the PVN of SHR were increased. PVN CRF-expressing neurons were expressed with chemogenetic DREADDs and PVN presympathetic neurons were retrogradely labeled with fluorescent tracer in WKY rats and SHR. In SHR expressed with chemogenetic inhibitory hM4Di-mCherry of PVN CRF-expressing neurons, bath application of CNO to the brain slices resulted in a significant decrease in sEPSCs frequency, but no change in their amplitude of labeled PVN presympathetic neurons. In contrast, in WKY rats expressed with excitatory hM3Dq-eGFP of PVN CRF-expressing neurons, CNO had no obvious effect on the sEPSCs frequency and amplitude in PVN presympathetic neurons. Furthermore, bath application of CNO had no significant effect on current-evoked firing of PVN presympathetic neurons of either WKY rats with hM3Dq-eGFP expression in CRF neurons or SHR with hM4Di-mCherry expression in CRF neurons. Conclusions The activity and number of PVN CRF-expressing neurons are increased in SHR, and CRF-expressing neurons enhance the excitability of presympathetic neurons, which acts as a regulatory neuronal microcircuit between CRF neurons and presympathetic neurons in the PVN.

15.
Chinese Journal of Pathology ; (12): 902-906, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1012332

RESUMEN

Objective: To investigate the histopathological and immunohistochemical characteristics of benign apocrine cystic papillary hyperplasia of the breast with loss of myoepithelial cell layer. Methods: The clinical data, histopathological features and immunohistochemical profile of patients with benign apocrine cystic papillary hyperplasia of breast with loss of myoepithelial cell layer from January 2016 to December 2021 were examined, in which six patients were identified. Results: All six patients were female, aged 36-61 years (median 46 years), who presented with a breast mass; three cases were from the left breast and three cases were from the right breast. Microscopic examination of all cases showed breast hyperplasia with apocrine cysts, accompanied by different degrees of micropapillary and papillary hyperplasia of apocrine cells. One case was associated with lobular carcinoma in situ, and one case was associated with apocrine ductal carcinoma in situ with intraductal dissemination in adenosis. Immunohistochemical staining of CK5/6, p63, SMA, SMMHC, Calponin and CD10 showed complete absence of myoepithelial cell layer surrounding ducts in apocrine cystic papillary hyperplasia. Conclusions: The myoepithelial cells of apocrine cystic papillary hyperplasia of the breast may undergo abnormal changes and may even be completely lost. The diagnosis should be comprehensively considered along with cytomorphological and histological features to avoid overdiagnosis.


Asunto(s)
Femenino , Humanos , Adulto , Persona de Mediana Edad , Células Epiteliales/patología , Hiperplasia/patología , Papiloma/patología , Glándulas Mamarias Humanas/patología , Neoplasias de la Mama/patología , Carcinoma Lobular/complicaciones , Carcinoma Ductal/complicaciones
16.
Acta Physiologica Sinica ; (6): 487-496, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1007763

RESUMEN

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.


Asunto(s)
Ratas , Animales , Ratas Endogámicas SHR , Núcleo Hipotalámico Paraventricular/fisiología , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Ratas Endogámicas WKY , Hormona Liberadora de Corticotropina/metabolismo , Neuronas/fisiología , Hipertensión , Sistema Nervioso Simpático
17.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-965248

RESUMEN

@#By regulating gene expression, nucleic acid drugs functioning in the cytoplasm or nucleus are of great significance in the treatment of acquired or inherited diseases and vaccine development.A variety of nucleic acid delivery vectors currently developed are suffering from low transfection efficiency due to endosome/lysosome entrapment.This paper introduces and summarizes the nucleic acid delivery strategies that bypass the endosomal/lysosomal pathway, including membrane translocation, membrane fusion, receptor/transporter-mediated non-endocytic uptake and caveolae-mediated endocytosis, and discusses the problems and challenges facing such strategies, aiming to facilitate the development of intracellular delivery of nucleic acid drugs bypassing lysosomal pathway.

18.
Acta Physiologica Sinica ; (6): 137-150, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-970114

RESUMEN

The solute carrier family 4 (SLC4) includes 10 members (SLC4A1-5, SLC4A7-11), which are expressed in multiple tissues in the human body. The SLC4 family members differ in their substrate dependence, charge transport stoichiometry and tissue expression. Their common function is responsible for the transmembrane exchange of multiple ions, which is involved in many important physiological processes, such as erythrocyte CO2 transport and the regulation of cell volume and intracellular pH. In recent years, many studies have focused on the role of SLC4 family members in the occurrence of human diseases. When SLC4 family members have gene mutations, a series of functional disorders will occur in the body, leading to the occurrence of some diseases. This review summarizes the recent progress about the structures, functions and disease correlation of SLC4 members, in order to provide clues for the prevention and treatment of related human diseases.


Asunto(s)
Humanos , Mutación , Proteínas SLC4A/fisiología
19.
Chinese Journal of School Health ; (12): 1226-1229, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-985594

RESUMEN

Objective@#To explore the relationship between handgrip strength (HGS) and pulmonary function (PF) in college students with sedentary lifestyle, so as to provide a reference for taking HGS as an essential factor of PF.@*Methods@#In March 1-5, 2023, a total of 44 college students were recruited and were divided into the sedentary group (22) and exercise group (22) according to the International Physical Activity Questionaire (IPAQ), with 22 students in each group. Independent sample t-test was used to compare the indexes between groups, pearson correlation coefficient was used to determine the correlation between HGS and PF. Multiple linear regression analysis was used to determine the predictive model of PF.@*Results@#There were statistical significance of the correlations between HGS and FVC, MEP, PEF, FEV1, FIVC, MIP, and PIF ( r=0.79, 0.47, 0.44, 0.60, 0.72, 0.53 , 0.49, P <0.01). When gender, physical activity, age, height, weight, and HGS were included as predictors in the regression model, height and HGS had significant effects on FVC ( R 2=0.75, F= 60.55 , P <0.01), weight and HGS had a good predictive effect on FIVC ( R 2=0.67, F=41.77, P <0.01).@*Conclusion@#HGS is significantly associated with PF in college students with sedentary lifestyle. Therefore, HGS can be used as an important indicator to predict the PF status of habitual sedentary college students.

20.
Journal of Forensic Medicine ; (6): 596-600, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1009392

RESUMEN

Wound age estimation is the core content in the practice of forensic medicine. Accurate estimation of wound age is a scientific question that needs to be urgently solved by forensic scientists at home and abroad. Metabolomics techniques can effectively detect endogenous metabolites produced by internal or external stimulating factors and describe the dynamic changes of metabolites in vivo. It has the advantages of strong operability, high detection efficiency and accurate quantitative results. Machine learning algorithm has special advantages in processing high-dimensional data sets, which can effectively mine biological information and truly reflect the physiological, disease or injury state of the body. It is a new technical means for efficiently processing high-throughput big data. This paper reviews the status and advantages of metabolomic techniques combined with machine learning algorithm in the research of wound age estimation, and provides new ideas for this research.


Asunto(s)
Algoritmos , Aprendizaje Automático , Medicina Legal , Metabolómica , Macrodatos
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