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1.
J Pain Res ; 17: 1381-1391, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38618296

RESUMEN

Purpose: Chinese herbal medicine and electroacupuncture (EA) have been used to control pain for many decades in China. We aim to explore the efficacy of intervening patients whose discogenic sciatica symptoms lasting longer than 3 months with these conservative treatments. Patients and Methods: This is a single-center, parallel-group, patient-unblinded Randomized Controlled Trial (RCT) with blinded outcome assessment and statistician. One hundred and twenty-four patients will be assigned randomly into 2 groups including conservative treatment group (Shenxie Zhitong capsule combined with EA treatment) and Nonsteroidal Anti-inflammatory Drugs (Nonsteroidal Anti-inflammatory Drugs, NSAIDs) control group (Celecoxib) in a 1:1 ratio. The trial involves a 4-week treatment along with follow-up for 6 months. The primary outcome is the leg pain intensity measured by the visual analogue scale (VAS) at 6 months after randomization. Secondary outcomes include leg pain intensity at other time points, back pain intensity, leg pain and back pain frequency, functional status, quality of life, return to work status and satisfaction of patients. Adverse events will also be recorded. Strengths and Limitations of This Study: Through this study, we want to observe the efficacy of electroacupuncture combined with Chinese herbal medicine on pain intensity for chronic sciatica secondary to Lumbar Disc Herniation. If the final results are favorable, it is expected to be a safe, economical, and effective treatment for patients. The study design has the following limitations: the setup of control group was less than perfect; patients and doctors could not be blinded in this trial; we skipped the feasibility study. We have tried our best to minimize adverse impacts. Trial Registration: ChiCTR2300070884 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 25th April 2023).

2.
Small ; : e2309940, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38534030

RESUMEN

Ferroptosis is an iron-dependent and lipid peroxides (LPO)-overloaded programmed damage cell death, induced by glutathione (GSH) depletion and glutathione peroxide 4 (GPX4) inactivation. However, the inadequacy of endogenous iron and reactive oxygen species (ROS) restricts the efficacy of ferroptosis. To overcome this obstacle, a near-infrared photo-responsive FeP@PEG NPs is fabricated. Exogenous iron pool can enhance the effect of ferroptosis via the depletion of GSH and further regulate GPX4 inactivation. Generation of ·OH derived from the Fenton reaction is proved by increased accumulation of lipid peroxides. The heat generated by photothermal therapy and ROS generated by photodynamic therapy can enhance cell apoptosis under near-infrared (NIR-808 nm) irradiation, as evidenced by mitochondrial dysfunction and further accumulation of lipid peroxide content. FeP@PEG NPs can significantly inhibit the growth of several types of cancer cells in vitro and in vivo, which is validated by theoretical and experimental results. Meanwhile, FeP@PEG NPs show excellent T2-weighted magnetic resonance imaging (MRI) property. In summary, the FeP-based nanotheranostic platform for enhanced phototherapy/ferroptosis/chemodynamic therapy provides a reliable opportunity for clinical cancer theranostics.

3.
Behav Brain Res ; 465: 114943, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38452974

RESUMEN

The normal aging process is accompanied by cognitive decline, and previous studies have indicated the crucial role of the hypothalamus in regulating both aging and cognition. However, the precise molecular mechanism underlying this relationship remains unclear. Therefore, this present study aimed to identify potential predictors of cognitive decline associated with aging specifically within the hypothalamus. To achieve this, we employed Morris water maze (MWM) testing to assess learning and memory differences between young and aged mice. Additionally, transcriptome sequencing was conducted on the hypothalamus of young and aged mice to identify potential genes. Subsequently, GO and KEGG analyses were performed to investigate the functions of differentially expressed genes (DEGs) and their associated biological pathways. Finally, the results obtained from sequencing analysis were further validated using qRT-PCR. Notably, MWM testing revealed a significant decrease in spatial learning and memory ability among aged mice. According to KEGG analysis, the DEGs primarily encompassed various biochemical signaling pathways related to immune system (e.g., C3; C4b; Ccl2; Ccl7; Cebpb; Clec7a; Col3a1; Cxcl10; Cxcl2; Fosb; Fosl1; Gbp5; H2-Ab1; Hspa1a; Hspa1b; Icam1; Il1b; Itga5; Itgax; Lilrb4a; Plaur; Ptprc; Serpine1; Tnfrsf10b; Tnfsf10), neurodegenerative disease (e.g., Atp2a1; Creb5; Fzd10; Hspa1a; Hspa1b; Il1b; Kcnj10; Nxf3; Slc6a3; Tubb6; Uba1y; Wnt9b), nervous system function (e.g., Chrna4; Chrna6; Creb5; Slc6a3),and aging (e.g., Creb5; Hspa1a; Hspa1b) among others. These identified genes may serve as potential predictors for cognitive function in elderly individuals and will provide a crucial foundation for further exploration into the underlying molecular mechanisms.


Asunto(s)
Disfunción Cognitiva , Enfermedades Neurodegenerativas , Humanos , Ratones , Animales , Anciano , Perfilación de la Expresión Génica , Envejecimiento/genética , Disfunción Cognitiva/genética , Hipotálamo , Transcriptoma
4.
Phytomedicine ; 128: 155490, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38460358

RESUMEN

BACKGROUND: Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Rubiaceae) is widely used to treat respiratory diseases in China. Strictosamide is its main active component and has significant anti-inflammatory activity. However, the effects and molecular mechanisms of strictosamide in the treatment of acute lung injury (ALI) remain largely unknown. PURPOSE: This study aimed to examine the regulatory effects of strictosamide on T helper 17 cells (Th17 cells)/Regulatory T cells (Treg cells) and gut microbiota in ALI-affected mice. MATERIALS AND METHODS: The ALI model was induced using lipopolysaccharide (LPS) intraperitoneal injection. Hematoxylin-eosin (H&E) staining, the number of inflammatory cells in broncho-alveolar lavage fluid (BALF), the Wet/Dry (W/D) ratio, and myeloperoxidase (MPO) activity were utilized as evaluation indices for the therapeutic efficacy of strictosamide on ALI. Flow cytometry (FCM), enzyme-linked immune sorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting were used to determine the regulation of strictosamide on the Th17/Treg cells and the STAT3/STAT5 signaling pathway. The analysis of gut microbiota was conducted using 16S rDNA sequencing. The verification of the relationship between the gut microbiome and immune function was conducted using Spearman analysis. RESULTS: Strictosamide attenuated inflammation on ALI induced by LPS, which reduced the levels of Th17-related factors interleukin (IL)-6 and IL-17 and increased Treg-related factors IL-10 and transforming growth factor (TGF)-ß. In the spleens and whole blood, strictosamide reduced the proportion of Th17 cells and increased the proportion of Treg cells. Furthermore, strictosamide increased Forkhead/winged helix transcription factor 3 (Foxp3) and p-STAT5 protein expression while inhibiting Retinoid-related orphan nuclear receptors-γt (RORγt) and p-STAT3 expression. Moreover, strictosamide reshaped the diversity and structure of the gut microbiota, and influence the associations between immune parameters and gut microbiota in ALI mice. CONCLUSIONS: In summary, the results of the current investigation showed that strictosamide has a therapeutic impact on LPS-induced ALI. The mechanism of action of this effect may be associated with the modulation of Th17 and Treg cells differentiation via the SATA signaling pathway, as well as the impact of the gut microbiota.


Asunto(s)
Lesión Pulmonar Aguda , Microbioma Gastrointestinal , Lipopolisacáridos , Factor de Transcripción STAT3 , Linfocitos T Reguladores , Células Th17 , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Linfocitos T Reguladores/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Células Th17/efectos de los fármacos , Masculino , Ratones , Factor de Transcripción STAT3/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Líquido del Lavado Bronquioalveolar/citología
5.
J Ethnopharmacol ; 325: 117830, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38301983

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L., a traditional Chinese medicine called "Kuzhi" in China, was used traditionally to treat liver diseases (eg. icterus, hepatitis) as well as malaria, asthma, and rheumatism. AIM OF THE STUDY: Our study aimed to investigate the withanolides with anti-hepatic fibrosis effect from P. angulate. MATERIALS AND METHODS: Withanolides were obtained from the EtOH extract of P. angulate by bioassay-molecular networking analysis-guided isolation using column chromatography and normal/reversed-phase semipreparative HPLC. The structures of new withanolides were elucidated by combinations of spectroscopic techniques with NMR and ECD calculations. MTT cell viability assay, AO/EB staining method, cell wound healing assay, ELISA and Western blot experiments were employed to evaluate the anti-hepatic fibrosis activity and to uncover related mechanism. Molecular docking analysis and cellular thermal shift assay were used to evaluate and verify the interaction between the active withanolides and their potential targets. RESULTS: Eight unreported withanolides, withagulides A-H (1-8), along with twenty-eight known ones were obtained from P. angulate. Withanolides 6, 9, 10, 24, 27, and 29-32 showed marked anti-hepatic fibrosis effect with COL1A1 expression inhibition above 50 %. Physalin F (9), the main component in the active fraction, significantly decreased the TGF ß1-stimulated expressions of collagen I and α-SMA in LX-2 cells. Mechanism study revealed that physalin F exerted its anti-hepatic fibrosis effect via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: This study suggested that withanolides were an important class of natural products with marked anti-hepatic fibrosis effect. The main withanolide physalin F might be a promising candidate for hepatic fibrosis treatment. The work provided experimental foundation for the use of P. angulate to treat hepatic fibrosis.


Asunto(s)
Physalis , Witanólidos , Witanólidos/farmacología , Witanólidos/uso terapéutico , Witanólidos/química , Physalis/química , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química
6.
J Sci Food Agric ; 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38415843

RESUMEN

Zinc, a crucial trace element is vital for the growth and development of humans. It is frequently described as 'the flower of life' and 'the source of intelligence'. Zinc supplements play a pivotal role in addressing zinc deficiency by serving as a vital source of this essential micronutrients, effectively replenishing depleted zinc levels in the body. In this paper, we first described the biological behavior of zinc in the human body and briefly described the physiological phenomena associated with zinc levels. The benefits and drawbacks of various zinc supplement forms are then discussed, with emphasis on the most recent zinc supplement formulations. Finally, the application of zinc supplements in food, medicine, and animal husbandry is further summarized. © 2024 Society of Chemical Industry.

7.
Mycoses ; 67(1): e13671, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37897073

RESUMEN

BACKGROUND: Hyperthermia is a common monotherapy for sporotrichosis, but only in patients with special conditions, such as pregnancy and nursing. However, hyperthermia has not been used more widely for sporotrichosis in clinical practice. PATIENTS/METHODS: An HIV-positive adult male with lymphocutaneous sporotrichosis caused by Sporothrix globosa that did not respond to conventional itraconazole therapy lasting >2 months received adjunctive therapy with local hyperthermia. To simulate the effects of heat exposure on the growth and morphology of Sporothrix spp. in vitro, S. globosa, S. schenckii and S. brasiliensis were exposed to intermittent heat (42°C) for 1 h a day for 7 or 28 days and observed under transmission electron microscopy. RESULTS: Itraconazole combined with local hyperthermia significantly improved the lesions, and the patient was successfully cured of sporotrichosis, with no recurrence after 2 years of follow-up. Cultures of Sporothrix spp. treated with 7 days of daily heat exposure in vitro showed obvious decreases in colony diameters, but not numbers, compared with untreated cultures (p < .001). After 28 days of heat exposure in vitro, Sporothrix spp. were unable to thrive (p < .001), and ultrastructural alterations, including loose cell wall structure, incomplete cell membrane, disrupted vacuoles and fragmented nuclei, were noticeable. CONCLUSIONS: Our case findings and in vitro experiments on Sporothrix spp., together with a literature review of previous sporotrichosis cases, suggest that hyperthermia has a clinical role as a treatment adjunct. Large-scale clinical trials are required to examine the utility of hyperthermia in various forms of cutaneous sporotrichosis.


Asunto(s)
Infecciones por VIH , Hipertermia Inducida , Sporothrix , Esporotricosis , Adulto , Humanos , Masculino , Esporotricosis/tratamiento farmacológico , Esporotricosis/patología , Itraconazol/uso terapéutico , Itraconazol/farmacología , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico
8.
J Tradit Complement Med ; 13(6): 538-549, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38020547

RESUMEN

Background and aim: Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway. Experimental procedure: The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN. Results and conclusion: The most frequent Chinese medicine component in XLW was Coptis chinensis. Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.

9.
Medicine (Baltimore) ; 102(41): e35399, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37832117

RESUMEN

BACKGROUND: To compare the effect of different noninvasive external therapies of traditional Chinese medicine (TCM) on the prevention of postpartum urinary retention (PUR) using a network meta-analysis (NMA). METHODS: A search of the China National Knowledge Infrastructure, WanFangDate, VIP, China Biomedical Literature Database, PubMed, The Cochrane Library, Embase, and Web of Science databases were reviewed for related randomized controlled trials dated between database inception and December 31, 2022, on the prevention of PUR by noninvasive TCM. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies; then, a NMA was performed using Revman5.3 software, State13.1 software, and frequency methodology. RESULTS: In total, 16 studies involving 3637 cases of parturients and 9 types of noninvasive TCM external treatments were incorporated into the NMA. The NMA results show that based on routine nursing, in terms of reducing the incidence of urinary retention, acupoint compressing combined with auricular acupressure is ranked first, followed by acupoint hot compress, acupoint massage combined with auricular acupressure, Yin-Yang therapy, acupoint massage, auricular acupressure, acupoint compressing, and routine nursing. In terms of urination time, acupoint compressing combined with auricular acupressure ranked first, followed by acupoint massage combined with auricular acupressure, acupoint electrical stimulation, acupoint compressing, TCM heating therapy, acupoint massage, auricular acupressure, and routine nursing. In terms of reducing residual urine volume after the first urination, acupoint compressing combined with auricular acupressure was ranked first, followed by auricular acupressure, acupoint compressing, acupoint massage, TCM heating therapy, and routine nursing. CONCLUSION: Current evidence shows that acupoint compressing combined with auricular acupressure may be the best noninvasive TCM treatment for preventing PUR based on routine nursing; however, further high-quality clinical randomized controlled trials are needed for validation and support.


Asunto(s)
Acupresión , Terapia por Acupuntura , Retención Urinaria , Humanos , Femenino , Embarazo , Medicina Tradicional China , Metaanálisis en Red , Retención Urinaria/etiología , Retención Urinaria/prevención & control , Terapia por Acupuntura/métodos , Acupresión/métodos , Parto Obstétrico
10.
Int J Mol Sci ; 24(13)2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37445900

RESUMEN

Potato is the world's fourth largest food crop. Due to limited arable land and an ever-increasing demand for food from a growing population, it is critical to increase crop yields on existing acreage. Soil salinization is an increasing problem that dramatically impacts crop yields and restricts the growing area of potato. One possible solution to this problem is the development of salt-tolerant transgenic potato cultivars. In this work, we review the current potato planting distribution and the ways in which it overlaps with salinized land, in addition to covering the development and utilization of potato salt-tolerant cultivars. We also provide an overview of the current progress toward identifying potato salt tolerance genes and how they may be deployed to overcome the current challenges facing potato growers.


Asunto(s)
Solanum tuberosum , Solanum tuberosum/genética , Tolerancia a la Sal/genética , Suelo
11.
Acta Pharmacol Sin ; 44(11): 2151-2168, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37420104

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg-1·d-1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 µM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aß generation by inhibiting the ß-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aß plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aß generation in early AD, which is a potential therapeutic intervention for early AD treatment.


Asunto(s)
Enfermedad de Alzheimer , Neuroblastoma , Enfermedades Neurodegenerativas , Ratones , Humanos , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Ácido Aspártico Endopeptidasas/metabolismo , Ratones Transgénicos , Retina/metabolismo , Modelos Animales de Enfermedad , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo
12.
Phytomedicine ; 116: 154863, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37236048

RESUMEN

BACKGROUND: Ellagitannins (ETs) are a major classification of natural tannins, with relatively large and complex structures. ETs from medicinal plants are focused increasingly due to urolithins, a kind of intestinal metabolite of ETs, which showed promising anti-Alzheimer's disease (AD) effects. Melastoma dodecandrum (MD), a widely used traditional Chinese medicine is rich in ETs, but their chemistry and potential neuroprotective effects have not been investigated. PURPOSE: This study aimed to identify the chemical composition of ETs in the crude extract of MD and to investigate their neuroprotective effects in vivo. METHODS: UPLC-QTOF-MS-based molecular networking (MN) and structural characterization were applied to targeted profiling of the MD-ETs. Animal behavior experiments, including the novel object recognition test (NOR), open field test (OFT), and Morris water maze test (MWM), were conducted to assess the memory improvement effects of MD-ETs in AD model mice. RESULTS: A total of 70 ETs, ranging from monomers to tetramers, were tracked and characterized in the MD extract using MN-guided targeted profiling, with 59 of them reported for the first time in this species. MD-ETs significantly improved memory impairment in AD mice, as indicated by decreased escape latency, increased number of crossings and target quadrant distance in MWM, increased rearing number in OFT, and increased preference index in NOR. CONCLUSION: This study systematically characterized the composition and structural features of ETs in MD using targeted LC-MS profiling, expanding the chemical information of ETs in MD. Furthermore, the results demonstrate that MD-ETs have significant effects on improving impaired memory in AD mice, suggesting their potential as alternative natural medicines for the treatment of neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer , Fármacos Neuroprotectores , Ratones , Animales , Taninos Hidrolizables/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Taninos
13.
Cell Rep ; 42(3): 112200, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36867532

RESUMEN

Thalamoreticular circuitry plays a key role in arousal, attention, cognition, and sleep spindles, and is linked to several brain disorders. A detailed computational model of mouse somatosensory thalamus and thalamic reticular nucleus has been developed to capture the properties of over 14,000 neurons connected by 6 million synapses. The model recreates the biological connectivity of these neurons, and simulations of the model reproduce multiple experimental findings in different brain states. The model shows that inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness. We find that thalamic interactions are responsible for the characteristic waxing and waning of spindle oscillations. In addition, we find that changes in thalamic excitability control spindle frequency and their incidence. The model is made openly available to provide a new tool for studying the function and dysfunction of the thalamoreticular circuitry in various brain states.


Asunto(s)
Tálamo , Vigilia , Ratones , Animales , Tálamo/fisiología , Sueño/fisiología , Núcleos Talámicos/fisiología , Percepción , Corteza Cerebral/fisiología
14.
Front Genet ; 14: 1079631, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36760992

RESUMEN

Background: Our aim was to determine the potential pharmacological mechanisms of the Guizhi decoction (GZD) in the treatment of osteoarthritis (OA) through an integrated approach of network pharmacological analyses, RNA sequencing (RNA-seq), and experimental validation. Methods: The quality control and identification of bioactive compounds of the GZD were carried out by using ultra-performance liquid chromatography (UPLC), and their OA-related genes were identified through overlapping traditional Chinese medicine systems pharmacology database (TCMSP), DrugBank and SEA Search Server databases, and GeneCards. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were implemented after constructing the component-target network. RNA-seq was used to screen differentially expressed genes (DEGs) under intervention conditions with and without the GZD in vitro. The crossover signaling pathways between RNA-seq and network pharmacology were then analyzed. Accordingly, protein-protein interaction (PPI) networks, GO, and KEGG analysis were performed using the Cytoscape, STRING, or DAVID database. The OA rat model was established to further verify the pharmacological effects in vivo. Hematoxylin-eosin (H&E) and safranin O/fast green (S-O) staining were used to grade the histopathological features of the cartilage. We verified the mRNA and protein expressions of the key targets related to the TNF signaling pathways in vivo and in vitro by qPCR, Western blotting (WB), and immunofluorescence assay. In addition, we also detected inflammatory cytokines in the rat serum by Luminex liquid suspension chip, which included tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß). Results: Eighteen compounds and 373 targets of the GZD were identified. A total of 2,356 OA-related genes were obtained from the GeneCards database. A total of three hub active ingredients of quercetin, kaempferol, and beta-sitosterol were determined, while 166 target genes associated with OA were finally overlapped. The RNA-seq analysis revealed 1,426 DEGs. In the KEGG intersection between network pharmacology and RNA-seq analysis, the closest screening relevant to GZD treatment was the TNF signaling pathway, of which TNF, IL-6, and IL-1ß were classified as hub genes. In consistent, H&E and S-O staining of the rat model showed that GZD could attenuate cartilage degradation. When compared with the OA group in vivo and in vitro, the mRNA levels of TNF-α, IL-1ß, IL-6, matrix metalloproteinase 3 (MMP3), and matrix metalloproteinase 9 (MMP9) were all downregulated in the GZD group (all p < 0.05). The expression levels of anabolic proteins (Col2α1 and SOX9) were all higher in the GZD group than in the OA group (p < 0.05), while the expression levels of the catabolic proteins (MMP9 and COX-2) and TNF-α in the GZD group were significantly lower than those in the OA group (p < 0.05). In addition, the expression levels of TNF, IL-6, and IL-1ß were upregulated in the OA group, while the GZD group prevented such aberrations (p < 0.01). Conclusion: The present study reveals that the mechanism of the GZD against OA may be related to the regulation of the TNF signaling pathway and inhibition of inflammatory response.

15.
Phytomedicine ; 112: 154709, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36774843

RESUMEN

BACKGROUND: Mailuo Shutong Pills (MLST) have displayed pharmacological activity against thromboangiitis obliterans (TAO). However, the active ingredients and therapeutic mechanism of MLST against TAO remained to be further clarified. PURPOSE: The aim of this study was to explore the active components of MLST and their synergistic mechanism against TAO by integrating pharmacokinetics (PK) and pharmacometabolomics (PM). METHODS: TAO model rats were established by sodium laurate solution. Firstly, the efficacy of MLST was evaluated by gangrene score, blood flow velocity, and hematoxylin-eosin (H&E) staining. Secondly, PK research was conducted on bioavailable components to characterize their dynamic behaviors under TAO. Thirdly, multiple plasma and urine metabolic biomarkers for sodium laurate-induced TAO rats were found by untargeted metabolomics, and then variations in TAO-altered metabolites following MLST treatment were analyzed utilizing multivariate and bioinformatic analysis. Additionally, metabolic pathway analysis was performed using MetaboAnalyst. Finally, the dynamic link between absorbed MLST-compounds and TAO-associated endogenous metabolites was established by correlation analysis. RESULTS: MLST significantly alleviated gangrene symptoms by improving the infiltration of inflammatory cells and blood supply in TAO rats. Significant differences in metabolic profiles were found in 17 differential metabolites in plasma and 24 in urine between Sham and TAO rats. The 10 bioavailable MLST-compounds, such as chlorogenic acid and paeoniflorin, showed positive or negative correlations with various TAO-altered metabolites related to glutamate metabolism, histidine metabolism, arachidonic acid metabolism and so on. CONCLUSION: This study originally investigated the dynamic interaction between MLST and the biosystem, providing unique insight for disclosing the active components of MLST and their synergistic mechanisms against TAO, which also shed light on new therapeutic targets for TAO and treatment.


Asunto(s)
Medicina Tradicional de Asia Oriental , Tromboangitis Obliterante , Ratas , Animales , Tromboangitis Obliterante/tratamiento farmacológico , Tromboangitis Obliterante/inducido químicamente , Gangrena , Tipificación de Secuencias Multilocus
16.
Clin Endocrinol (Oxf) ; 98(5): 682-691, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36746677

RESUMEN

OBJECTIVES: To quantify the effect of carnitine on glucose and lipid metabolic profiles and fertility outcomes in women with Polycystic ovary syndrome (PCOS). DESIGN: A systematic review and meta-analysis were conducted. PATIENTS: Women with PCOS diagnosed by Rotterdam or Androgen Excess Society (AES) criteria and taking carnitine supplement were assessment. MEASUREMENTS: Fertility outcomes (ovulation, clinical pregnancy, live birth, and miscarriage), lipid parameters (BMI, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein), fasting glucose and insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). RESULTS: In total, 839 participants were included in this analysis. The dosage of carnitine and treatment duration reported by studies varied from 250 mg to 3000 mg daily and 84 to 90 days, respectively. The publication bias was absent. Compared with placebo, carnitine significantly improved ovulation rates (RR 3.42, 95% CI 2.39 to 4.89, I2 = 0%) and pregnancy rates (RR 11.05, 95% CI 1.21 to 100.58, I2 = 79%). None of included studies reported live birth. After treatment, carnitine resulted in significant reductions relative to baseline in body mass index (BMI, MD -0.93 kg/m2, 95% CI -1.15 to -0.70, I2 = 55.0%), insulin levels (MD -2.47 mIU/L, 95% CI -4.49 to -0.45, I2 = 0%) and the Homeostasis Model Assessment index (MD -0.67, 95% CI -1.20 to -0.14, I2 = 0%) than placebo, but not for lipid profiles including triglyceride, total cholesterol, and low-density lipoprotein. CONCLUSION: With the available literature, carnitine seems to improve ovulation and clinical pregnancy and insulin resistance, BMI in women with PCOS. These effects are warranted to be further validated, due to insufficient statistical power.


Asunto(s)
Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Embarazo , Femenino , Humanos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Glucosa , Carnitina , Fertilidad , Insulina , Lipoproteínas LDL , Triglicéridos , Colesterol , Lípidos
17.
Adv Healthc Mater ; 12(4): e2202307, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36349844

RESUMEN

Safe and effective strategies are urgently needed to fight against the life-threatening diseases of various cancers. However, traditional therapeutic modalities, such as radiotherapy, chemotherapy and surgery, exhibit suboptimal efficacy for malignant tumors owing to the serious side effects, drug resistance and even relapse. Phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), are emerging therapeutic strategies for localized tumor inhibition, which can produce a large amount of reactive oxygen species (ROS) or elevate the temperature to initiate cell death by non-invasive irradiation. In consideration of the poor bioavailability of phototherapy agents (PTAs), lots of drug delivery systems have been developed to enhance the tumor targeted delivery. Nevertheless, the carriers of drug delivery systems inevitably bring biosafety concerns on account of their metabolism, degradation, and accumulation. Of note, carrier-free nanomedicine attracts great attention for clinical translation with synergistic antitumor effect, which is characterized by high drug loading, simplified synthetic method and good biocompatibility. In this review, the latest advances of phototherapy with various carrier-free nanomedicines are summarized, which may provide a new paradigm for the future development of nanomedicine and tumor precision therapy.


Asunto(s)
Neoplasias , Fotoquimioterapia , Humanos , Nanomedicina , Fototerapia , Neoplasias/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Línea Celular Tumoral , Nanomedicina Teranóstica
18.
Animal ; 16(12): 100676, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36442324

RESUMEN

Fermented feed has the potential to improve poultry gastrointestinal microecological environment, health condition and production performance. Thus, the present study was undertaken to explore the effects of fermented feed on the laying performance, egg quality, immune function, intestinal morphology and microbiota of laying hens in the late laying cycle. A total of 360 healthy Hy-Line Brown laying hens aged 80 weeks were used to conduct a 56-day study. All hens were randomly separated into two treatment groups, with five replicates of 36 hens each as follows: basal diet containing 0.0% fermented feed (CON) and 20% fermented feed (FF). Subsequent analyses revealed that fermented feed supplementation was associated with significant increases in laying rates together with reduced broken egg rates and feed conversion ratio for hens in FF group (P < 0.05). There were additionally significant increases in both albumen height and Haugh unit values in hens following fermented feed supplementation (P < 0.05). Fermented feed was also associated with increases in duodenal, jejunal and ileac villus height (P < 0.05). Laying hens fed fermented feed had higher immune globulin (Ig)A, IgG, IgM levels (P < 0.01,) and higher interleukin 2, interleukin 6, tumour necrosis factor α and interferon γ (P < 0.05) concentrations than CON. Analysis of the microbiota in these laying hens revealed the alpha diversity was not significantly affected by fermented feed supplementation. Firmicutes abundance was reduced in caecal samples from FF hens relative to those from CON hens (30.61 vs 35.12%, P < 0.05). At the genus level, fermented feed was associated with improvements in relative Lactobacillus, Megasphaera and Peptococcus abundance and decreased Campylobacter abundance in laying hens. These results suggest that fermented feed supplementation may be beneficial to the laying performance, egg quality, immunological function, intestinal villus growth and caecal microecological environment of laying hens at the end of the laying cycle.


Asunto(s)
Suplementos Dietéticos , Microbiota , Animales , Femenino , Alimentación Animal/análisis , Pollos , Dieta/veterinaria , Suplementos Dietéticos/análisis , Inmunidad
20.
World J Clin Cases ; 10(27): 9961-9963, 2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36186206

RESUMEN

To achieve awareness of the initiative practice for health concept in the Chinese population, traditional Chinese medicine (TCM) doctors should popularize TCM culture and knowledge among young people, people with a low level of education, in low-income populations, and in rural populations.

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