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1.
Mol Med ; 29(1): 168, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38093172

RESUMEN

BACKGROUND: Shenqi Compound (SQC) has been used in clinic for several decades in the prevention and treatment of diabetes and its complications. But this is merely a heritage of experience. The primary aim of this study is to scientifically validate the therapeutic effects of SQC on diabetic vascular calcification (DVC) in an animal model and, simultaneously, uncover its potential underlying mechanisms. METHOD: Spontaneous diabetic rat- Goto Kakizaki (GK) rats were selected for rat modeling. We meticulously designed three distinct groups: a control group, a model group, and an SQC treatment group to rigorously evaluate the influence of SQC. Utilizing a comprehensive approach that encompassed methods such as pathological staining, western blot analysis, qRT-PCR, and RNA sequencing, we thoroughly investigated the therapeutic advantages and the underlying mechanistic pathways associated with SQC in the treatment of DVC. RESULT: The findings from this investigation have unveiled the extraordinary efficacy of SQC treatment in significantly mitigating DVC. The underlying mechanisms driving this effect encompass multifaceted facets, including the restoration of aberrant glucose and lipid metabolism, the prevention of phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteogenic-like states, the subsequent inhibition of cell apoptosis, the modulation of inflammation responses, the remodeling of the extracellular matrix (ECM), and the activation of the Hippo-YAP signaling pathway. Collectively, these mechanisms lead to the dissolution of deposited calcium salts, ultimately achieving the desired inhibition of DVC. CONCLUSION: Our study has provided compelling and robust evidence of the remarkable efficacy of SQC treatment in significantly reducing DVC. This reduction is attributed to a multifaceted interplay of mechanisms, each playing a crucial role in the observed therapeutic effects. Notably, our findings illuminate prospective directions for further research and potential clinical applications in the field of cardiovascular health.


Asunto(s)
Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Calcificación Vascular , Ratas , Animales , Estudios Prospectivos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Diabetes Mellitus Tipo 2/metabolismo , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/complicaciones , Calcificación Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo
2.
J Cardiovasc Pharmacol ; 81(4): 300-316, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36701487

RESUMEN

ABSTRACT: Vascular endothelial cells, which make up the inner wall of blood arteries, are susceptible to damage from oxidative stress and apoptosis caused by hyperglycemia. According to certain reports, noncoding RNAs are involved in controlling oxidative stress and apoptosis. ShenQi Compound (SQC), a traditional herbal remedy, has been successfully treating diabetic vascular disease in China for more than 20 years. Although it is well established that SQC protects the vascular endothelium, the molecular mechanism remains unknown. Goto-Kakizaki rats, spontaneous type II diabetes rats, that consistently consume a high-fat diet were chosen as model animals. Six groups (control group, model group, metformin group, and 7.2 g/kg/d SQC group, 14.4 g/kg/d SQC group, and 28.8 g/kg/d SQC group) were included in this work, 15 rats each group. The approach of administration was gavage, and the same volume (5.0 mL/kg/d) was given in each group, once a day, 12 weeks. The thoracic aortas were removed after the rats were sacrificed. Oxidative reduction profile in thoracic aorta, histopathological observation of thoracic aorta, endothelial cell apoptosis in thoracic aorta, whole transcriptome sequencing, bioinformatic analyses, and qRT-PCR were conducted. As a result, SQC prevented the oxidative stress and apoptosis induced by a high glucose concentration. Under hyperglycemia condition, noncoding RNAs, including 1 downregulated novel circRNA (circRNA.3121), 3 downregulated lncRNAs (Skil.cSep08, Shawso.aSep08-unspliced, and MSTRG.164.2), and 1 upregulated mRNA (Pcdh17), were clearly reverse regulated by SQC. SQC plays a role in protecting vascular endothelial cells from high glucose mainly by mediating ncRNA to inhibit cell apoptosis and oxidative stress.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , ARN Largo no Codificante , Ratas , Animales , ARN Largo no Codificante/genética , ARN Circular , ARN Mensajero/genética , Células Endoteliales , Secuenciación del Exoma , Glucosa
3.
Phytother Res ; 37(10): 4587-4606, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37353982

RESUMEN

Ferroptosis, an iron-dependent cell death characterized by lethal lipid peroxidation, is involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Therefore, ferroptosis inhibition represents an attractive strategy for COPD therapy. Herein, we identified natural flavonoid scutellarein as a potent ferroptosis inhibitor for the first time, and characterized its underlying mechanisms for inhibition of ferroptosis and COPD. In vitro, the anti-ferroptotic activity of scutellarein was investigated through CCK8, real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, flow cytometry, and transmission electron microscope (TEM). In vivo, COPD was induced by lipopolysaccharide (LPS)/cigarette smoke (CS) and assessed by changes in histopathological, inflammatory, and ferroptotic markers. The mechanisms were investigated by RNA-sequencing (RNA-seq), electrospray ionization mass spectra (ESI-MS), local surface plasmon resonance (LSPR), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and molecular dynamics. Our results showed that scutellarein significantly inhibited Ras-selective lethal small molecule (RSL)-3-induced ferroptosis and mitochondria injury in BEAS-2B cells, and ameliorated LPS/CS-induced COPD in mice. Furthermore, scutellarein also repressed RSL-3- or LPS/CS-induced lipid peroxidation, GPX4 down-regulation, and overactivation of Nrf2/HO-1 and JNK/p38 pathways. Mechanistically, scutellarein inhibited RSL-3- or LPS/CS-induced Fe2+ elevation through directly chelating Fe2+ . Moreover, scutellarein bound to the lipid peroxidizing enzyme arachidonate 15-lipoxygenase (ALOX15), which resulted in an unstable state of the catalysis-related Fe2+ chelating cluster. Additionally, ALOX15 overexpression partially abolished scutellarein-mediated anti-ferroptotic activity. Our findings revealed that scutellarein alleviated COPD by inhibiting ferroptosis via directly chelating Fe2+ and interacting with ALOX15, and also highlighted scutellarein as a candidate for the treatment of COPD and other ferroptosis-related diseases.


Asunto(s)
Apigenina , Ferroptosis , Enfermedad Pulmonar Obstructiva Crónica , Ratones , Animales , Araquidonato 15-Lipooxigenasa/metabolismo , Lipopolisacáridos , Enfermedad Pulmonar Obstructiva Crónica/patología , Quelantes del Hierro , Hierro
4.
Molecules ; 28(4)2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36838978

RESUMEN

The kidney is an important organ in the human body, with functions such as urine production, the excretion of metabolic waste, the regulation of water, electrolyte and acid-base balance and endocrine release. The morbidity and mortality of kidney diseases are increasing year by year worldwide, and they have become a serious public health problem. In recent years, natural products derived from fungi, plants and animals have become an important alternative source of treatment for kidney diseases because of their multiple pathways, multiple targets, safety, low toxicity and few side effects. Tanshinone IIA (Tan IIA) is a lipid-soluble diterpene quinone isolated from the Chinese herb Salvia miltiorrhiza, considered as a common drug for the treatment of cardiovascular diseases. As researchers around the world continue to explore its unknown biological activities, it has also been found to have a wide range of biological effects, such as anti-cancer, anti-oxidative stress, anti-inflammatory, anti-fibrotic, and hepatoprotective effects, among others. In recent years, many studies have elaborated on its renoprotective effects in various renal diseases, including diabetic nephropathy (DN), renal fibrosis (RF), uric acid nephropathy (UAN), renal cell carcinoma (RCC) and drug-induced kidney injury caused by cisplatin, vancomycin and acetaminophen (APAP). These effects imply that Tan IIA may be a promising drug to use against renal diseases. This article provides a comprehensive review of the pharmacological mechanisms of Tan IIA in the treatment of various renal diseases, and it provides some references for further research and clinical application of Tan IIA in renal diseases.


Asunto(s)
Abietanos , Enfermedades Renales , Animales , Humanos , Abietanos/farmacología , Extractos Vegetales/farmacología , Riñón , Enfermedades Renales/tratamiento farmacológico , Fibrosis
5.
Zhongguo Zhong Yao Za Zhi ; 47(4): 1120-1125, 2022 Feb.
Artículo en Zh | MEDLINE | ID: mdl-35285213

RESUMEN

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , China , Medicamentos Herbarios Chinos/uso terapéutico , Prescripciones , Salud Pública
6.
Environ Sci Technol ; 55(14): 9721-9729, 2021 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-34196183

RESUMEN

Soil has always been the most complex biomaterial on the planet. The rapid determination of the components in the soil and their original source is a prerequisite for soil quality, environmental, and human health risk assessments. In this study, the chemical compositions and source apportionment of surface soil samples collected from five sites in Shanghai, China, were successfully investigated using a laboratory-developed laser ablation single-particle aerosol mass spectrometry (LA-SPAMS) instrument combined with an adaptive resonance theory-based neural network algorithm (ART-2a) data-processing method for the first time. In total, more than 35,000 particles, ranging from 200 to 2000 nm, were sized, and around 15-20% of the particles were chemically analyzed by LA-SPAMS to generate both positive and negative mass spectra. The results show that there are significant differences in particle size distribution among the five samples, with peaks of various sizes and different profiles, while all five soil samples contain crustal elements, heavy metals, organic and inorganic components, and so forth. The chemical composition of each sample varied considerably, so different classes of SPAMS particle classes were identified, which were later grouped into seven general categories: EC-rich (containing elemental carbon), secondary components, organic nitrogen, crust, HM (containing heavy metal), PAH (containing polycyclic aromatic hydrocarbons), and NaK-rich particles, based on the dominant marked ions. The composition analysis and source apportionment showed that soil components in different areas have been affected by the local environment, such as local industrial emissions and automobile exhaust, which are usually characterized by varying degrees of mixing between the crust and environmental aerosols. In combination with the ART-2a method, LA-SPAMS enables rapid and direct analysis of soil samples based on real-time single-particle measurements, which will help in understanding the distribution, transport, and fate of the soil components, thus providing new insights into soil-quality assessment. Moreover, the established LA-SPAMS can also be practically applied to other daily inspection tasks, such as rocks, minerals, metals, ceramics, polymers, and other solid materials for ingredient analysis and quality evaluation.


Asunto(s)
Contaminantes Atmosféricos , Terapia por Láser , Metales Pesados , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , China , Monitoreo del Ambiente , Humanos , Espectrometría de Masas , Metales Pesados/análisis , Tamaño de la Partícula , Material Particulado/análisis , Suelo
7.
Phytother Res ; 35(2): 587-602, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32939932

RESUMEN

This study aims to evaluate the efficacy and safety of Qiming granule (QG) on diabetic macular edema (DME). PubMed, Embase, the Cochrane Library, CNKI, Wanfang, qvip and China Biology Medicine Disc were searched. Randomized controlled trials (RCTs) about participants with a diagnosis of DME were included. Risk of bias assessment was conducted by Cochrane risk-of-bias tool for RCT. Random-effects model was implemented to pool results. Among 16 included studies, QG combined with conventional treatment was administered 13.5 g daily for a period ranging from 2 to 6 months. Results showed combination therapy was more effective than conventional treatment alone in central macular thickness (weighted mean difference (WMD) = -29.43, 95% confidence interval (CI) (-39.56 to -19.29), p = .0001), optimum corrected vision (pooled standardized mean difference (SMD) = -0.962, 95%CI (-1.35 to -0.57), p = .0001) and overall effective rate (RR = 1.25, 95%CI = [1.13 to 1.35], p < .0001). Only three studies reported adverse effects. The quality of evidence is low. Due to a lack of placebo control, the net efficacy of QG is still uncertain. More high-quality RCTs are needed to confirm the efficacy and safety of QG in DME.


Asunto(s)
Retinopatía Diabética/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Edema Macular/tratamiento farmacológico , Medicamentos sin Prescripción/uso terapéutico , Quimioterapia Combinada , Humanos , Medicina Tradicional China , Fitoterapia , Ensayos Clínicos Controlados Aleatorios como Asunto
8.
Zhongguo Zhong Yao Za Zhi ; 45(4): 709-714, 2020 Feb.
Artículo en Zh | MEDLINE | ID: mdl-32237469

RESUMEN

Guided by the basic theory of traditional Chinese medicine and using modern scientific methods, Dao-di herbs pharmacology studies the nature, performance, interaction with the body and its clinical application.It is a bridge between the basic research and clinical application of Dao-di herbs. It can objectively describe the law of efficacy of Dao-di herbs, scientifically explain the mechanism of efficacy of Dao-di herbs, explore and establish the standards and methods of Dao-di herbs based on biological effect and clinical efficacy, and provide scientific basis for the special properties, pharmacology and clinical value of Dao-di herbs.Furthermore, we put forward a new idea of building the standard of Dao-di herbs based on the curative effect rather than the origin.The Dao-di herbs standard should come from the systematic research of traditional Dao-di herbs producing areas and form a new characteristic system, through the extraction of environmental, genetic, character, chemical, pharmacological and other characteristics.This standard originates from the tradition, but it is higher than the tradition. It may not have the origin meaning of strict administrative division, but it can better reflect the pharmacological characteristics and excellent clinical value of Dao-di herbs.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/normas , Plantas Medicinales/química , China , Medicina Tradicional China
9.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(9): 1078-85, 2014 Sep.
Artículo en Zh | MEDLINE | ID: mdl-25335332

RESUMEN

OBJECTIVE: To investigate the protective effect and mechanism of Shenqi Compound on diabetic angiopathy modeled rats. METHODS: Totally 18 SD rats were randomized into 3 groups, i.e., the normal control group, the diabetic mellitus (DM) group, and Shenqi Compound group, 6 in each group. The DM rat model was established by feeding high-fat diet (to induce hyperlipidemia) +intraperitoneal injection of small dose streptozotocin (STZ). Shenqi Compound was given to rats in the Shenqi Compound group at the daily dose of 2 g/kg. Equal volume of normal saline was given to rats in the model group and the normal control group by gastrogavage. All treatment was lasted for 12 weeks. Then 2-D and ultrasonic integrated backscatter technique were used to evaluate structural and functional changes of abdominal aorta in the progression of diabetic macroangiopathy. The fibrosis degree of the aorta vessel and myocardium capillaries were observed by using HE and Masson trichrome staining. The tension of the aortic vascular ring was determined. The transforming growth factor beta (TGF-beta) mRNA expression was detected by real time PCR (RT-PCR). The protein expression of TGF-beta, collagen I, collagen III, connective tissue growth factor (CTGF), and phosphorylation P38 MAPK were detected by Western blot. RESULTS: Compared with the normal control group, abdominal aortic systolic inner diameter, diastolic inner diameter, Peterson elastic modulus, stiffness index, and backscatter integral significantly increased; the rangeability of integral backscatter and the extension coefficient of cross section significantly decreased in the DM group (all P < 0.05). After 12 weeks aforesaid indices were obviously improved in the Shenqi Compound group (P < 0.05). Results of HE and Masson staining showed that the fibrosis degree of the aorta vessel and myocardium capillaries was obviously alleviated in rats of the Shenqi Compound group (P < 0.05). Results of the aortic vascular ring tension showed that acetylcholine induced vasodilatation and maximum diastolic percent were obviously elevated in the Shenqi Compound group (P < 0.05). Compared with the normal control group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all significantly increased in the DM group (P < 0.05). Compared with the DM group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all decreased (P < 0.05). CONCLUSIONS: Shenqi Compound could effectively improve the arterial function in diabetic marcoangiopathy and microvascular dysfunction. The mechanism might be due to the down-regulating the expression of TGF-beta, and further suppressing the phosphorylation of P38 MAPK, reducing the synthesis of collagen I and collagen III, therefore, ameliorating arterial and myocardial interstitial fibrosis.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Angiopatías Diabéticas/prevención & control , Medicamentos Herbarios Chinos/farmacología , Animales , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
10.
Front Pharmacol ; 15: 1349244, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38708085

RESUMEN

Introduction: Herbal formulations are renowned for their complex biological activities, acting on multiple targets and pathways, as evidenced by in vitro studies. However, the hypoglycemic effect and underlying mechanisms of Shenqi Compound (SQ), a traditional Chinese herbal formula, remain elusive. This study aimed to elucidate the hypoglycemic effects of SQ and explore its mechanisms of action, focusing on intestinal flora and metabolomics. Methods: A Type 2 diabetes mellitus (T2DM) rat model was established through a high-fat diet, followed by variable glucose and insulin injections to mimic the fluctuating glycemic conditions seen in diabetes. Results: An eight-week regimen of SQ significantly mitigated hyperglycemia, inflammation, and insulin resistance in these rats. Notably, SQ beneficially modulated the gut microbiota by increasing populations of beneficial bacteria, such as Lachnospiraceae_NK4A136_group and Akkermansia, while reducing and inhibiting harmful strains such as Ruminococcus and Phascolarctobacterium. Metabolomics analyses revealed that SQ intervention corrected disturbances in Testosterone enanthate and Glycerophospholipid metabolism. Discussion: Our findings highlight the hypoglycemic potential of SQ and its mechanisms via modulation of the gut microbiota and metabolic pathways, offering a theoretical foundation for the use of herbal medicine in diabetes management.

11.
Diabetes Ther ; 15(3): 585-609, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38302838

RESUMEN

Diabetic macroangiopathy, a prevalent and severe complication of diabetes mellitus, significantly contributes to the increased morbidity and mortality rates among affected individuals. This complex disorder involves multifaceted molecular mechanisms that lead to the dysfunction and damage of large blood vessels, including atherosclerosis (AS) and peripheral arterial disease. Understanding the intricate pathways underlying the development and progression of diabetic macroangiopathy is crucial for the development of effective therapeutic interventions. This review aims to shed light on the molecular mechanism implicated in the pathogenesis of diabetic macroangiopathy. We delve into the intricate interplay of chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulated angiogenesis, all of which contribute to the vascular complications observed in this disorder. By exploring the molecular mechanism involved in the disease we provide insight into potential therapeutic targets and strategies. Moreover, we discuss the current therapeutic approaches used for treating diabetic macroangiopathy, including glycemic control, lipid-lowering agents, and vascular interventions.

12.
Eur J Mass Spectrom (Chichester) ; : 14690667241252020, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38706124

RESUMEN

This paper presents a newly developed high-performance mobile single-photon ionization time-of-flight mass spectrometry (M-SPI-TOFMS) system for on-line analysis and stereoscopic monitoring of complex gas mixtures. The system is designed for stereoscopic imaging to map the distribution of volatile organic compounds (VOCs) and trace their emission sources in urban areas and industrial parks. It mainly consists of a SPI-TOFMS instrument, a customized commercial vehicle, a meteorological five-parameter monitor with GPS, a high-power generator, and an uninterruptible power supply. The SPI technique, using a 118 nm VUV lamp, can ionize compounds with an ionization potential below 10.78 eV. Mass spectra obtained using this technique show the profiles of various VOCs and some inorganic compounds. The VOCs composition information and mobile location data are simultaneously sent to the GIS software. In GIS software, this data is used for real-time stereoscopic imaging of VOC distribution and precise tracking of VOC movement. The system can achieve a spatial data resolution of 0.69 mm at 25 km/h due to the microsecond detection speed of the M-SPI-TOFMS instrument. The laboratory test provides a rapid overview characterization of benzene, toluene, and xylene. The M-SPI-TOFMS has limits of detection and mass resolution of 33.7 pptv and 1060, respectively. Several field applications were carried out using M-SPI-TOFMS at various locations to identify VOC sources near different factories. The M-SPI-TOFMS system has a navigation monitoring speed of 25 km/h with a time resolution of 1 s. The widespread use of this system will provide accurate data to support environmental management departments in formulating VOCs pollution control policies and improving control efficiency.

13.
Talanta ; 277: 126327, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38805944

RESUMEN

Single photon ionization time-of-flight mass spectrometry (SPI-TOF-MS) is a powerful analytical technique for real-time detection of trace VOCs. However, efficient ion transmission within the ionization chamber has always been a challenging issue in SPI-TOF-MS. In this study, a novel ion guide termed the Segmented Focus Quadrupole Ion Guide (SFQ-IG) was introduced for SPI-TOF-MS. The SFQ-IG device consists of 12 printed circuit boards (PCB), each containing four quarter-ring electrodes with inner diameters progressively decreasing from 26 to 4 mm. The simulation results demonstrated that SFQ-IG exhibited superior ion transmission efficiency than both ion funnel (IF) field and direct current-only (DC-only) field. By integrating into a SPI-TOF-MS, this ion guide was optimized in terms of the ionization source pressure, direct current gradient, and radio frequency amplitude. Further comparative experiments demonstrated that the SPI-TOF-MS with the SFQ-IG exhibited higher sensitivity than both the IF field (1.3-7.4 times) and DC-only field (3.5-8.8 times) for the test VOCs. The improvements in limit of detection (LOD) with the SFQ-IG ranged from 1.6 to 5.3 times compared to the DC-only field for the test VOCs. Fabricated using PCB technology, the SFQ-IG is characterized by its cost-effectiveness, compact size, and high transmission efficiency, facilitating its integration into other mass spectrometers.

14.
Chem Biol Interact ; 396: 111037, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38719172

RESUMEN

Breast cancer (BC) is the most common cancer in women and is known for its tendency to spread to the bones, causing significant health issues and mortality. In this study, we aimed to investigate whether cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles (ISL@ZLH NPs) could inhibit BC-induced bone destruction and tumor metastasis in both in vitro and animal models. To evaluate the potential of ISL@ZLH NPs, we conducted various experiments. First, we assessed cell viability, colony formation, transwell migration, and wound healing assays to determine the impact of ISL@ZLH NPs on BC cell behavior. Western blotting, TRAP staining and ALP activity were performed to examine the effects of ISL@ZLH NPs on osteoclast formation induced by MDA-MB-231 cell-conditioned medium and RANKL treated RAW 264.7 cells. Furthermore, we assessed the therapeutic impact of ISL@ZLH NPs on tumor-induced bone destruction using a mouse model of BC bone metastasis. Treatment with ISL@ZLH NPs effectively suppressed BC cell proliferation, colony formation, and motility, reducing their ability to metastasize. ISL@ZLH NPs significantly inhibited osteoclast formation and the expression of factors associated with bone destruction in BC cells. Additionally, ISL@ZLH NPs suppressed JAK-STAT signaling in RAW264.7 cells. In the BCBM mouse model, ISL@ZLH NPs led to a significant reduction in osteolytic bone lesions compared to the control group. Histological analysis and TRAP staining confirmed that ISL@ZLH NPs preserved the integrity of bone structure, preventing invasive metastasis by confining tumor growth to the bone marrow cavity. Furthermore, ISL@ZLH NPs effectively suppressed tumor-induced osteoclastogenesis, a key process in BC-related bone destruction. Our findings demonstrate that ISL@ZLH NPs have the potential to inhibit BC-induced bone destruction and tumor metastasis by targeting JAK-STAT signaling pathways and suppressing tumor-induced osteoclastogenesis. These results underscore the therapeutic promise of ISL@ZLH NPs in managing BC metastasis to the bones.


Asunto(s)
Neoplasias Óseas , Neoplasias de la Mama , Chalconas , Quinasas Janus , Nanopartículas , Fosfatidilcolinas , Factores de Transcripción STAT , Transducción de Señal , Zeína , Animales , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Ratones , Quinasas Janus/metabolismo , Nanopartículas/química , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Transducción de Señal/efectos de los fármacos , Humanos , Factores de Transcripción STAT/metabolismo , Línea Celular Tumoral , Chalconas/farmacología , Chalconas/química , Chalconas/uso terapéutico , Zeína/química , Fosfatidilcolinas/química , Fosfatidilcolinas/farmacología , Proliferación Celular/efectos de los fármacos , Células RAW 264.7 , Movimiento Celular/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos
15.
Biomed Pharmacother ; 170: 116072, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38147739

RESUMEN

In recent years, the widespread prevalence of diabetes has become a major killer that threatens the health of people worldwide. Of particular concern is hyperglycemia-induced vascular endothelial injury, which is one of the factors that aggravate diabetic vascular disease. During the process of diabetic vascular endothelial injury, apoptosis is an important pathological manifestation and autophagy is a key regulatory mechanism. Autophagy and apoptosis interact with each other. Hence, the crosstalk mechanism between the two processes is an important means of regulating diabetic vascular endothelial injury. This article reviews the research progress in apoptosis in the context of diabetic vascular endothelial injury and discusses the crosstalk mechanism of autophagy and apoptosis and its role in this injury. The purpose is to guide the prevention and treatment of diabetic vascular endothelial injury in the future.


Asunto(s)
Diabetes Mellitus Experimental , Hiperglucemia , Animales , Humanos , Apoptosis , Autofagia/fisiología , Proteínas Reguladoras de la Apoptosis , Hiperglucemia/complicaciones
16.
Front Pharmacol ; 15: 1339406, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38659573

RESUMEN

Type 2 diabetes presents a significant global health burden and is frequently linked to serious clinical complications, including diabetic cardiomyopathy, nephropathy, and retinopathy. Astragalus polysaccharide (APS), extracted from Astragalus membranaceus, exhibits various biochemical and physiological effects. In recent years, a growing number of researchers have investigated the role of APS in glucose control and the treatment of diabetes and its complications in various diabetes models, positioning APS as a promising candidate for diabetes therapy. This review surveys the literature on APS from several databases over the past 20 years, detailing its mechanisms of action in preventing and treating diabetes mellitus. The findings indicate that APS can address diabetes by enhancing insulin resistance, modulating the immune system, protecting islet cells, and improving the intestinal microbiota. APS demonstrates positive pharmacological value and clinical potential in managing diabetic complications, including diabetic retinopathy, nephropathy, cardiomyopathy, cognitive dysfunction, wound healing, and more. However, further research is necessary to explore APS's bioavailability, optimal dosage, and additional clinical evidence.

17.
Phytomedicine ; 129: 155663, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759345

RESUMEN

BACKGROUNDS: Allergic rhinitis (AR) is a non-infectious chronic inflammation of the nasal mucosa mainly mediated by immunoglobulin E (IgE) in atopic individuals after exposure to allergens. The application of AR guideline-recommended pharmacotherapies can rapidly relieve symptoms of AR but with poor long-term efficacy, and many of these therapies have side effects. Many natural products and their derivatives have shown potential therapeutic effects on AR with fewer side effects. OBJECTIVES: This review aims to expand understanding of the roles and mechanisms of natural compounds in the treatment of AR and to highlight the importance of utilizing natural products in the treatment of AR. MATERIAL AND METHOD: We conducted a systematic literature search using PubMed, Web of Science, Google Scholar, and Clinical Trials. The search was performed using keywords including natural products, natural compounds, bioproducts, plant extracts, naturally derived products, natural resources, allergic rhinitis, hay fever, pollinosis, nasal allergy. Comprehensive research and compilation of existing literature were conducted. RESULTS: This article provided a comprehensive review of the potential therapeutic effects and mechanisms of natural compounds in the treatment of AR. We emphasized that natural products primarily exert their effects by modulating signalling pathways such as NF-κB, MAPKs, STAT3/ROR-γt/Foxp3, and GATA3/T-bet, thereby inhibiting the activation and expansion of allergic inflammation. We also discussed their toxicity and clinical applications in AR therapy. CONCLUSION: Taken together, natural products exhibit great potential in the treatment of AR. This review is also expected to facilitate the application of natural products as candidates for treating AR. Furthermore, drug discovery based on natural products has a promising prospect in AR treatment.


Asunto(s)
Productos Biológicos , Rinitis Alérgica , Humanos , Rinitis Alérgica/tratamiento farmacológico , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Fitoterapia , Animales , Transducción de Señal/efectos de los fármacos , Inmunoglobulina E
18.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(3): 351-5, 2013 Mar.
Artículo en Zh | MEDLINE | ID: mdl-23713249

RESUMEN

OBJECTIVE: To observe the effects of Shenqi Compound (SQC) on the mRNA expression of angiotensin II type 1 receptor (AT1R) in the aorta of Goto-Kakizaki (GK) rats. METHODS: Totally 67 GK rats were randomly divided into 5 groups, i.e., the GK group (n =18), the model group (n =16), the atorvastatin group (n =17), and the SQC group (n =16). Another a normal control group was set up (n =18). The diabetic macrovascular disease model was prepared by adding L-NAME (at the daily dose of 0.10 mg/mL) in drinking water for GK rats. GK rats, except those in the normal control group were fed with high fat diet. Atorvastatin (at the daily dose of 1.60 mg/kg) and SQC (at the daily dose of 1.44 g/kg) were respectively administered by gastrogavage, once daily for 35 successive days. The blood glucose was determined by glucose oxidase method once per week. After 5-week medication, the contents of triglyceride (TG) and total cholesterol (TC) were determined by ELISA. The serum concentrations of angiotensin I (Ang II) were determined by RIA. The mRNA expression of AT1R in the aorta was determined by real-time quantitative reverse transcriptase PCR (RT-PCR). RESULTS: The blood glucose level was obviously lower in both the atorvastatin group and the SQC group after 4 weeks of medication (P <0.05). Besides, it was significantly lower in the SQC group than in the model group by the end of the 4th week (P <0.05). The concentrations of TG, TC and serum Ang II , and the mRNA expression of AT1R in the aorta were significantly higher in the model group than in the normal control group (P <0.01). After 5-week medication, the concentrations of TG, TC and serum Ang I , and the mRNA expression of AT1 R in the aorta were significantly lower in the atorvastatin group and the SQC group than in the model group (P <0.01, P <0.05). The mRNA expression of AT1R was significantly higher in the SQC group than in the atorvastatin group (P <0.05). CONCLUSIONS: SQC could significantly reduce the levels of blood glucose, TG, TC, down-regulate the mRNA expression of AT1R in the aorta, and decrease the expressions of serum Ang II of GK rats with diabetic macrovascular disease. AT1 R might be one of effective targets of SQC in treating diabetic macrovascular diseases.


Asunto(s)
Aorta/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Receptor de Angiotensina Tipo 1/metabolismo , Angiotensina II/sangre , Animales , Aorta/efectos de los fármacos , Glucemia/análisis , Colesterol/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Masculino , ARN Mensajero/genética , Ratas , Receptor de Angiotensina Tipo 1/genética , Triglicéridos/sangre
19.
Biomed Pharmacother ; 166: 115287, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37572639

RESUMEN

Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by impaired insulin secretion and insulin resistance, resulting in elevated blood glucose levels. The dysfunction and loss of pancreatic ß-cells, responsible for producing insulin, contribute to the development of T2D. Traditional Chinese medicine (TCM) has emerged as a potential source of innovative therapeutic interventions. However, limited research exists on Chinese herbal formulations specifically targeting the protection of pancreatic ß-cell function and mass. One such formulation is the Shenqi compound (SQC), widely used in China and consisting of Panax Ginseng, Astragali Radix, Rhizoma Dioscoreae, Corni Fructus, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Radix Trichosanthis, and Rhei Radix et Rhizoma. Understanding the mechanisms underlying the therapeutic effects of SQC is crucial for developing novel treatment strategies for T2D. This study aims to comprehensively investigate the scientific evidence supporting the role of SQC in alleviating T2D by targeting the protection of pancreatic ß-cell function and mass. Spontaneously diabetic GK rats were used as the animal model, receiving SQC (14.4 g/kg/d) for 8 weeks. The results demonstrate multiple beneficial effects of SQC, including significant control of blood glucose levels (P < 0.05), inhibition of insulin resistance (measured by Western Blot), reduction of hyperinsulinemia (P < 0.05), attenuation of oxidative stress (P < 0.05), suppression of inflammation (P < 0.05), protection against islet hypertrophy and beta cell proliferation (evaluated through pathological staining), and inhibition of ß-cell apoptosis and senescence (also assessed through pathological staining). These findings indicate the promotion of ß-cell survival and function. In vitro experiments using isolated islets further support these results, revealing improvements in insulin secretion (P < 0.05) and ß-cell function following SQC therapy (P < 0.05). This represents a significant breakthrough in addressing ß-cell dysfunction and preserving mass within the context of TCM. Overall, SQC shows promise as a natural therapeutic approach for T2D, with potential benefits in preserving pancreatic ß-cell function and mass. This enhances the practical applicability and significance of the research by bridging the gap between experimental findings and clinical practice, thereby providing important clinical value in TCM treatment of T2D. Further research is necessary to elucidate its precise mechanisms of action and optimize its clinical application.


Asunto(s)
Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Resistencia a la Insulina , Ratas , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucemia , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico
20.
Front Endocrinol (Lausanne) ; 14: 1191426, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37441493

RESUMEN

Vascular endothelial injury in diabetes mellitus (DM) is the major cause of vascular disease, which is closely related to the occurrence and development of a series of vascular complications and has a serious negative impact on a patient's health and quality of life. The primary function of normal vascular endothelium is to function as a barrier function. However, in the presence of DM, glucose and lipid metabolism disorders, insulin resistance, inflammatory reactions, oxidative stress, and other factors cause vascular endothelial injury, leading to vascular endothelial lesions from morphology to function. Recently, numerous studies have found that autophagy plays a vital role in regulating the progression of vascular endothelial injury. Therefore, this article compares the morphology and function of normal and diabetic vascular endothelium and focuses on the current regulatory mechanisms and the important role of autophagy in diabetic vascular endothelial injury caused by different signal pathways. We aim to provide some references for future research on the mechanism of vascular endothelial injury in DM, investigate autophagy's protective or injurious effect, and study potential drugs using autophagy as a target.


Asunto(s)
Diabetes Mellitus , Resistencia a la Insulina , Lesiones del Sistema Vascular , Humanos , Calidad de Vida , Estrés Oxidativo , Autofagia
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