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1.
Biology (Basel) ; 13(4)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38666864

RESUMO

This research sought to assess the effects of dietary supplements with Gracilaria lichenoides and Bacillus amyloliquefaciens, either individually or combined, on the growth performance, antioxidant capacity, and intestinal function of Penaeus monodon. A total of 840 shrimps were randomly assigned to 28 tanks with an average initial weight of (1.04 ± 0.03) g (30 shrimp per tank) with 7 different treatment groups and 4 replicates per treatment. The control treatment (C) consisted of a basal diet; in contrast, the experimental groups were complement with varying levels of G. lichenoides (3% or 8%), either alone (S3 and S8) or in combination with B.amyloliquefaciens at different concentrations (3% G. lichenoides and 109 CFU/g-S3B9; 8% G. lichenoides and 1011 CFU/g B. amyloliquefaciens-S8B11; 109 CFU/g B. amyloliquefaciens-S9; 1011 CFU/g B. amyloliquefaciens-B11). The results indicated that the maximum values of final body weight (FBW) (10.49 ± 0.90) g, weight gain rate (WGR) (908.94 ± 33.58) g, and specific growth rate (SGR) (4.20 ± 0.06) g were perceived in the 3% G. lichenoide diet treatment, and compared with the control group, the difference was significant (p < 0.05). The whole-body lipid content of shrimp in the B9 group was significantly higher than that in the B11 group (p < 0.05), but no significant difference was observed when compared with shrimp fed other diets (p > 0.05). The ash content of shrimp in the B9 group was found to be significantly higher than that in the S3B9 group (p < 0.05). Furthermore, the lipase activity in the stomach and intestines of the experimental groups exhibited a statistically significantly increase compared to the control (p < 0.05). In comparison to the control group, the hepatopancreas of the S3 group exhibited a significant increase in the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and antioxidant genes [SOD, catalase (CAT), GSH-Px, thioredoxin (Trx), Hippo, and NF-E2-related factor 2 (Nrf2)] expression levels (p < 0.05). Additionally, the activities of total antioxidant capacity (T-AOC), SOD, peroxidase (POD), and antioxidant genes (CAT, GSH-Px, Trx, and Hippo) in the S3B9 treatment of hepatopancreas showed significant improvement (p < 0.05). The inclusion of dietary G. lichenoides and B. amyloliquefaciens resulted in enhanced relative expression of intestinal lipid metabolism genes (fatty acid synthetase (FAS), lipophorin receptor (LR), fatty acid transport protein 1 (FATP1)) and suppressed the expression of the long-chain fatty acid-CoA ligase 4 (LCL4) gene. Analysis of microbiota sequencing indicated improvements in composition and structure, with notable increases in Firmicutes at the phylum level and Vibrio at the genus level in the S3 group, as well as an increase in Tenericutes at the genus level in the S8B11 group. Overall, the inclusion of dietary G. lichenoides and B. amyloliquefaciens positively impacted the growth, antioxidant capacity, and microbial composition of shrimp, with particular enhancement observed in shrimp fed a supplementary 3% G. lichenoides diet.

2.
Environ Toxicol ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613516

RESUMO

Coriander is a notable medicinal plant known for its diverse properties, including anti-inflammatory, antioxidant, anticancer, analgesic, and anti-diabetic effects. Despite its recognized health benefits, research on its nephroprotective properties is limited. This study aimed to investigate the potential nephroprotective properties of an aqueous extract derived from coriander leaves using an aristolochic acid-intoxicated zebrafish model. To assess kidney abnormalities induced by aristolochic acid (AA), we utilized the transgenic line Tg(wt1b:egfp), which expresses green fluorescent protein (GFP) in the kidney. Our previous report indicated that AA exposure leads to acute renal failure in zebrafish characterized by kidney malformation and impaired renal function. However, pretreatment of coriander extract (CE) can mitigate kidney malformations induced by AA. In addition, CE pretreatment reduces the accumulation of red blood cells in the glomerular region. To verify the nephroprotective effects of CE, we analyzed renal function by measuring the glomerular filtration rate in zebrafish embryos. Results indicate that CE partially mitigates renal function impairment caused by AA exposure, suggesting its potential to attenuate AA-induced renal failure. Mechanistically, pretreatment with CE reduces the expression of proinflammatory and proapoptotic genes induced by AA. This suggests that CE likely alleviates acute renal failure by reducing inflammation and apoptosis. As a result, we regard zebrafish as a valuable model for screening natural compounds that have the potential to alleviate AA-induced nephrotoxicity.

3.
Front Pharmacol ; 15: 1333087, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545553

RESUMO

Tumors are still a major threat to people worldwide. Nanodrug delivery and targeting systems can significantly improve the therapeutic efficacy of chemotherapeutic drugs for antitumor purposes. However, many nanocarriers are likely to exhibit drawbacks such as a complex preparation process, limited drug-loading capacity, untargeted drug release, and toxicity associated with nanocarriers. Therefore, new therapeutic alternatives are urgently needed to develop antitumor drugs. Natural products with abundant scaffold diversity and structural complexity, which are derived from medicinal plants, are important sources of new antitumor drugs. Here, two carrier-free berberine (BBR)-based nanoparticles (NPs) were established to increase the synergistic efficacy of tumor treatment. BBR can interact with glycyrrhetinic acid (GA) and artesunate (ART) to self-assemble BBR-GA and BBR-ART NPs without any nanocarriers, respectively, the formation of which is dominated by electrostatic and hydrophobic interactions. Moreover, BBR-GA NPs could lead to mitochondria-mediated cell apoptosis by regulating mitochondrial fission and dysfunction, while BBR-ART NPs induced ferroptosis in tumor cells. BBR-based NPs have been demonstrated to possess significant tumor targeting and enhanced antitumor properties compared with those of simple monomer mixes both in vitro and in vivo. These carrier-free self-assemblies based on natural products provide a strategy for synergistic drug delivery and thus offer broad prospects for developing enhanced antitumor drugs.

4.
Sci Total Environ ; 923: 171404, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38432381

RESUMO

Increased nitrogen deposition has important effects on below-ground ecological processes. Fine roots are the most active part of the root system in terms of physiological activity and the main organs for nutrient and water uptake by plants. However, there is still a limited understanding of how nitrogen deposition affects the fine root dynamics in subtropical Abies georgei (Orr) forests. Consequently, a three-year field experiment was conducted to quantify the effects of three forms of nitrogen sources ((NH4)2SO4, NaNO3, and NH4NO3) at four levels (0, 5, 15, and 30 kg N·ha-1·yr-1) on the fine root dynamics in Abies georgei forests using a randomized block-group experimental design and minirhizotron technique. The first year of nitrogen addition did not affect the first-class fine roots (FR1, 0 < diameter < 0.5 mm) and second-class fine roots (FR2, 0.5 < diameter < 1.0 mm). The next two years of nitrogen addition significantly increased the production, mortality, and turnover of FR1 and FR2; the three year of nitrogen addition did not affect the dynamics of the third- class fine roots (FR3, 1.0 < diameter < 1.5 mm) and fourth- class fine roots (FR4,1.5 < diameter < 2.0 mm). Nitrogen addition positively affected the dynamics of FR1, FR2, FR3 and FR4 by positively affecting the carbon, nitrogen, and phosphorus contents of fine roots and indirectly affecting the soil pH. Increased carbon allocation to FR1 and FR2 may represent a phosphorus acquisition strategy when nitrogen is not the limiting factor. The nitrogen addition forms and levels affected the fine root dynamics in the following orde: NH4NO3 > (NH4)2SO4 > NaNO3 and high nitrogen > medium nitrogen > low nitrogen. The results suggest that the different-diameter fine root dynamics respond differently to different nitrogen addition forms and levels, and linking the different-diameter fine roots to nitrogen deposition is crucial.


Assuntos
Abies , Nitrogênio , Nitrogênio/química , Raízes de Plantas , Florestas , Solo/química , Fósforo , Carbono , Biomassa , Ecossistema , Árvores
5.
Animals (Basel) ; 14(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38540057

RESUMO

To investigate the effects of individual essential amino acids (EAA) on growth and the underlying mechanisms, EAA individually supplemented a low-protein (LP) diet fed to young rats in the present study. Treatments were an LP diet that contained 6% crude protein (CP), a high-protein (HP) diet that contained 18% CP, and 10 LP diets supplemented with individual EAA to achieve an EAA supply equal to that of the HP diet. The CP concentration of the LP diet was ascertained from the results of the first experiment, which examined the effects of dietary CP concentrations on growth rates, with CP ranging from 2% to 26%. Weight gain was increased with the supplementation of His, Ile, Lys, Thr, or Trp as compared to the LP diet (p < 0.05). Feed intake was greater for the His-, Lys-, and Thr-supplemented treatments as compared to the LP group (p < 0.05). Protein utilization efficiency was lower for the HP group than other groups (p < 0.01). The supplementation of Leu, Lys, and Val led to reduced protein utilization efficiency (p < 0.05), but the supplementation of Thr and Trp led to greater efficiency than the LP group (p < 0.05). Compared to the LP group, plasma urea concentrations were elevated with individual EAA supplementation, with the exception of the Thr addition. The added EAA resulted in increased concentrations of the corresponding EAA in plasma, except for Arg and Phe supplementation. The supplementation of Arg, His, Leu, Lys, and Met individually stimulated mTORC1 pathway activity (p < 0.05), and all EAA resulted in the decreased expression of ATF4 (p < 0.05). In summary, the supplementation of His, Ile, Lys, Thr, or Trp to an LP diet improved the growth performance of young rats. Responses to His and Lys additions were related to the activated mTORC1 pathway and feed intake increases. The improved growth performance resulting from the addition of a single EAA is not solely attributed to the increased plasma availability of EAA. Rather, it may be the consequence of a confluence of factors encompassing signaling pathways, the availability of amino acids, and other associated elements. The additivity of these factors results in independent responses to several EAA with no order of limitation, as is universally encoded in growth models for all production animal species.

6.
Saudi Pharm J ; 32(4): 101980, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38439949

RESUMO

Xanthine oxidase (XO) has been widely recognized as a pivotal enzyme in developing hyperuricemia, primarily contributing to the excessive production of uric acid during purine metabolism in the liver. One of the standard treatment approaches involves reducing uric acid levels by inhibiting XO activity. In this study, the leaf extract of Dolichandrone spathacea, traditionally used in folk medicine, was found to inhibit XO activity in the ethyl acetate and butanol fractions at a concentration of 100 µg/mL, their values were 78.57 ± 3.85 % (IC50 = 55.93 ± 5.73 µg/ml) and 69.43 ± 8.68 % (IC50 = 70.17 ± 7.98 µg/ml), respectively. The potential XO inhibitory components were isolated by bioactivity assays and the HR-ESI-MS and NMR spectra system. The main constituents of leaf extracts of Dolichandrone spathacea, six compounds, namely trans-4-methoxycinnamic acid (3), trans-3,4-dimethoxycinnamic acid (4), p-coumaric acid (5), martynoside (6), 6-O-(p-methoxy-E-cinnamoyl)-ajugol (7), and scolymoside (17), were identified as potent XO inhibitors with IC50 values ranging from 19.34 ± 1.63 µM to 64.50 ± 0.94 µM. The enzyme kinetics indicated that compounds 3-5, 7, and 17 displayed competitive inhibition like allopurinol, while compound 6 displayed a mixed-type inhibition. Computational studies corroborated these experimental results, highlighting the interactions between potential metabolites and XO enzyme. The hydrogen bonds played crucial roles in the binding interaction, especially, scolymoside (17) forms a hydrogen bond with Mos3004, exhibited the lowest binding energy (-18.3286 kcal/mol) corresponding to the lowest IC50 (19.34 ± 1.63 µM). Furthermore, nine compounds were isolated for the first time from this plant. In conclusion, Dolichandrone spathacea and its constituents possess the potential to modulate the xanthine oxidase enzyme involved in metabolism.

7.
Hum Brain Mapp ; 45(2): e26582, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339904

RESUMO

Preclinical evidence suggests that inter-individual variation in the structure of the hypothalamus at birth is associated with variation in the intrauterine environment, with downstream implications for future disease susceptibility. However, scientific advancement in humans is limited by a lack of validated methods for the automatic segmentation of the newborn hypothalamus. N = 215 healthy full-term infants with paired T1-/T2-weighted MR images across four sites were considered for primary analyses (mean postmenstrual age = 44.3 ± 3.5 weeks, nmale /nfemale = 110/106). The outputs of FreeSurfer's hypothalamic subunit segmentation tools designed for adults (segFS) were compared against those of a novel registration-based pipeline developed here (segATLAS) and against manually edited segmentations (segMAN) as reference. Comparisons were made using Dice Similarity Coefficients (DSCs) and through expected associations with postmenstrual age at scan. In addition, we aimed to demonstrate the validity of the segATLAS pipeline by testing for the stability of inter-individual variation in hypothalamic volume across the first year of life (n = 41 longitudinal datasets available). SegFS and segATLAS segmentations demonstrated a wide spread in agreement (mean DSC = 0.65 ± 0.14 SD; range = {0.03-0.80}). SegATLAS volumes were more highly correlated with postmenstrual age at scan than segFS volumes (n = 215 infants; RsegATLAS 2 = 65% vs. RsegFS 2 = 40%), and segATLAS volumes demonstrated a higher degree of agreement with segMAN reference segmentations at the whole hypothalamus (segATLAS DSC = 0.89 ± 0.06 SD; segFS DSC = 0.68 ± 0.14 SD) and subunit levels (segATLAS DSC = 0.80 ± 0.16 SD; segFS DSC = 0.40 ± 0.26 SD). In addition, segATLAS (but not segFS) volumes demonstrated stability from near birth to ~1 years age (n = 41; R2 = 25%; p < 10-3 ). These findings highlight segATLAS as a valid and publicly available (https://github.com/jerodras/neonate_hypothalamus_seg) pipeline for the segmentation of hypothalamic subunits using human newborn MRI up to 3 months of age collected at resolutions on the order of 1 mm isotropic. Because the hypothalamus is traditionally understudied due to a lack of high-quality segmentation tools during the early life period, and because the hypothalamus is of high biological relevance to human growth and development, this tool may stimulate developmental and clinical research by providing new insight into the unique role of the hypothalamus and its subunits in shaping trajectories of early life health and disease.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Adulto , Recém-Nascido , Lactente , Humanos , Masculino , Feminino , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Hipotálamo/diagnóstico por imagem
8.
Br J Pharmacol ; 181(12): 1768-1792, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38355288

RESUMO

BACKGROUND AND PURPOSE: Panax ginseng is widely applied in the adjuvant treatment of cardiometabolic diseases in clinical practice without clear mechanisms. This study aims to clearly define the efficacy and underlying mechanism of P. ginseng and its active components in protecting against atherosclerosis. EXPERIMENTAL APPROACH: The anti-atherogenic efficacy of total ginseng saponin extract (TGS) and its components was evaluated on Ldlr-/- mice. Gut microbial structure was analysed by 16S rRNA sequencing and PCR. Bile acid profiles were revealed using targeted metabolomics with LC-MS/MS analysis. The contribution of gut microbiota to atherosclerosis was assessed by co-housing experiments. KEY RESULTS: Ginsenoside Rb1, representing protopanaxadiol (PPD)-type saponins, increased intestinal Lactobacillus abundance, resulting in enhanced bile salt hydrolase (BSH) activity to promote intestinal conjugated bile acid hydrolysis and excretion, followed by suppression of enterohepatic farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signal, and thereby increased cholesterol 7α-hydroxylase (CYP7A1) transcriptional expression and facilitated metabolic elimination of cholesterol. Synergistically, protopanaxatriol (PPT)-type saponins, represented by ginsenoside Rg1, protected against atherogenesis-triggered gut leak and metabolic endotoxaemia. Ginsenoside Rg1 directly induced mucin production to nutritionally maintain Akkermansia muciniphila, which reciprocally inhibited gut permeation. Rb1/Rg1 combination, rather than a single compound, can largely mimic the holistic efficacy of TGS in protecting Ldlr-/- mice from atherogenesis. CONCLUSION AND IMPLICATIONS: Our study provides strong evidence supporting TGS and ginsenoside Rb1/Rg1 combinations as effective therapies against atherogenesis, via targeting different signal nodes by different components and may provide some elucidation of the holistic mode of herbal medicines.


Assuntos
Aterosclerose , Microbioma Gastrointestinal , Ginsenosídeos , Homeostase , Camundongos Knockout , Panax , Animais , Ginsenosídeos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Masculino , Camundongos , Panax/química , Camundongos Endogâmicos C57BL , Ácidos e Sais Biliares/metabolismo , Receptores de LDL/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Amidoidrolases/metabolismo , Colesterol 7-alfa-Hidroxilase/metabolismo
9.
Plant Biotechnol J ; 22(6): 1536-1548, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38226779

RESUMO

Salvianolic acids (SA), such as rosmarinic acid (RA), danshensu (DSS), and their derivative salvianolic acid B (SAB), etc. widely existed in Lamiaceae and Boraginaceae families, are of interest due to medicinal properties in the pharmaceutical industries. Hundreds of studies in past decades described that 4-coumaroyl-CoA and 4-hydroxyphenyllactic acid (4-HPL) are common substrates to biosynthesize SA with participation of rosmarinic acid synthase (RAS) and cytochrome P450 98A (CYP98A) subfamily enzymes in different plants. However, in our recent study, several acyl donors and acceptors included DSS as well as their ester-forming products all were determined in SA-rich plants, which indicated that previous recognition to SA biosynthesis is insufficient. Here, we used Salvia miltiorrhiza, a representative important medicinal plant rich in SA, to elucidate the diversity of SA biosynthesis. Various acyl donors as well as acceptors are catalysed by SmRAS to form precursors of RA and two SmCYP98A family members, SmCYP98A14 and SmCYP98A75, are responsible for different positions' meta-hydroxylation of these precursors. SmCYP98A75 preferentially catalyses C-3' hydroxylation, and SmCYP98A14 preferentially catalyses C-3 hydroxylation in RA generation. In addition, relative to C-3' hydroxylation of the acyl acceptor moiety in RA biosynthesis, SmCYP98A75 has been verified as the first enzyme that participates in DSS formation. Furthermore, SmCYP98A enzymes knockout resulted in the decrease and overexpression leaded to dramatic increase of SA accumlation. Our study provides new insights into SA biosynthesis diversity in SA-abundant species and versatility of CYP98A enzymes catalytic preference in meta-hydroxylation reactions. Moreover, CYP98A enzymes are ideal metabolic engineering targets to elevate SA content.


Assuntos
Sistema Enzimático do Citocromo P-450 , Salvia miltiorrhiza , Hidroxilação , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Salvia miltiorrhiza/metabolismo , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/enzimologia , Polifenóis/metabolismo , Polifenóis/biossíntese , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Alcenos
10.
Medicine (Baltimore) ; 103(4): e35730, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277549

RESUMO

BACKGROUND: Propofol is a common regimen for general anesthesia maintenance. But propofol can dose-dependently generate cardiopulmonary depression. Thus, any strategy to reduce propofol dosage during laparoscopic surgery may have underlying beneficial effect for patient prognosis. Previous studies indicated both analgesic and sedative effect of acupoint stimulation. However, its main sedative effect on patients under general anesthesia remains unclear. OBJECTIVE: The aim of this study was to investigate the sedative effect of transcutaneous electrical acupoint stimulation (TEAS) on patients scheduled for laparoscopic surgery under general anesthesia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: In this randomized clinical trial, patients scheduled for laparoscopic surgery under general anesthesia in Xijing hospital were randomly assigned to 3 groups, receiving electrical stimulation at the Shenmen (HT7)/Ximen (PC4) (TEAS group), stimulation at the shoulder (non-acupoint group) or no stimulation (control group), respectively. MAIN OUTCOME MEASURES: One hundred sixty-two patients completed the study. The primary outcome was the consumption of propofol, and secondary outcomes included features of recovery after surgery, major complications after surgery and by 1 year after surgery. RESULTS: In patients undergoing laparoscopic surgery, the doses of propofol decreased significantly in the TEAS group compared (0.10 ±â€…0.02 mg·kg-1·min-1) with the other 2 groups (both 0.12 ±â€…0.02 mg·kg-1·min-1, P < .001). The mean differences (95% confidence interval) for non-acupoint versus TEAS and control versus TEAS were 0.021 (0.012, 0.030) and 0.024 (0.013, 0.034), respectively. Time to awake and to extubation were not significantly different among the groups. The incidences of major complications after surgery and by 1 year after surgery were not significantly different among the groups. CONCLUSION: TEAS could induce additional sedative effect in patients during laparoscopic surgery and reduce propofol consumption.


Assuntos
Laparoscopia , Propofol , Estimulação Elétrica Nervosa Transcutânea , Humanos , Pontos de Acupuntura , Hipnóticos e Sedativos
11.
J Ethnopharmacol ; 323: 117703, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38185260

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Aurantii (FA), a well-known phytomedicine, has been employed to evoke antidepressant and prokinetic multi-functions. Therein, systematically identifying bioactive components and the referred mechanism is essential for FA. AIM OF THE STUDY: This study was planned to answer "2 W" (What and Why), such as which components and pathways contribute to FA's multi-functions. We aimed to identify bioactive compounds as the key for opening the lock of FA's multi-functions, and the molecule mechanisms are their naturally matched lock cylinder. MATERIALS AND METHODS: The phytochemical content of FA extract was determined, and the compounds were identified in rats pretreated with FA using liquid chromatography with mass spectrometry (LC-MS). The contribution strategy was used to assess bioactive compounds' efficacy (doses = their content in FA) in model rats with the mechanism. The changes in functional brain regions were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD). RESULT: Eight phytochemicals' content was detected, and merely six components were identified in rats in vivo. Meranzin hydrate + hesperidin (MH), as the primary contributor of FA, exerted antidepressant and prokinetic effects (improvement of indexes for immobility time, gastric emptying, intestinal transit, CRH, ghrelin, ACTH, DA, NA, 5-HT, CORT, and 5-HT3) by regulating 5-HT3/Growth hormone secretagogue receptor (GHSR) pathway. These results were validated by 5-HT2A, 5-HT3, and GHSR receptor antagonists combined with molecule docking. MH restored the excessive BOLD activation of the left accumbens nucleus, left corpus callosum and hypothalamus preoptic region. CONCLUSION: Absorbed MH accounts for FA's anti-depressant and prokinetic efficacy in acutely-stressed rats, primarily via 5-HT3/GHSR shared regulation.


Assuntos
Medicamentos de Ervas Chinesas , Serotonina , Ratos , Animais , Ratos Sprague-Dawley , Receptores de Grelina , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia
12.
Int Immunopharmacol ; 127: 111345, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38086266

RESUMO

Triptolide (TPT) is widely used in the treatment of rheumatoid arthritis (RA). However, its regulatory mechanisms are not fully understood. This study demonstrated that Myeloid-derived suppressor cells (MDSCs) were expanded in both RA patients and arthritic mice. The frequency of MDSCs was correlated with RA disease severity and T helper 17 (Th17) responses. MDSCs from RA patients promoted the polarization of Th17 cells in vitro, which could be substantially attenuated by blocking arginase-1 (Arg-1). TPT inhibited the differentiation of MDSCs, particularly the monocytic MDSCs (M-MDSCs) subsets, as well as the expression of Arg-1 in a dose dependent manner. Alongside, TPT treatment reduced the potential of MDSCs to promote the polarization of IL-17+ T cell in vitro. Consistently, TPT immunotherapy alleviated adjuvant-induced arthritis (AIA) in a mice model, and reduced the frequency of MDSCs, M-MDSCs and IL-17+ T cells simultaneously. The presented data suggest a pathogenic role of MDSCs in RA and may function as a novel and effective therapeutic target for TPT in RA.


Assuntos
Artrite Reumatoide , Diterpenos , Células Supressoras Mieloides , Fenantrenos , Humanos , Animais , Camundongos , Células Supressoras Mieloides/metabolismo , Interleucina-17/metabolismo , Arginase/metabolismo , Artrite Reumatoide/metabolismo , Compostos de Epóxi
13.
J Nat Prod ; 87(1): 2-13, 2024 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-38117981

RESUMO

The glucose transporter 1 (GLUT1) protein is involved in the basal-level absorption of glucose in tumor cells. Inhibiting GLUT1 decreases tumor cell proliferation and induces tumor cell damage. Natural GLUT1 inhibitors have been studied only to a small extent, and the structures of known natural GLUT1 inhibitors are limited to a few classes of natural products. Therefore, discovering and researching other natural GLUT1 inhibitors with novel scaffolds are essential. Physalis angulata L. var. villosa is a plant known as Mao-Ku-Zhi (MKZ). Withanolides are the main phytochemical components of MKZ. MKZ extracts and the components of MKZ exhibited antitumor activity in recent pharmacological studies. However, the antitumor-active components of MKZ and their molecular mechanisms remain unknown. A cell membrane-biomimetic nanoplatform (CM@Fe3O4/MIL-101) was used for target separation of potential GLUT1 inhibitors from MKZ. A new withanolide, physagulide Y (2), together with six known withanolides (1, 3-7), was identified as a potential GLUT1 inhibitor. Physagulide Y was the most potent GLUT1 inhibitor, and its antitumor activity and possible mechanism of action were explored in MCF-7 human cancer cells. These findings advance the development of technologies for the targeted separation of natural products and identify a new molecular framework for the investigation of natural GLUT1 inhibitors.


Assuntos
Antineoplásicos Fitogênicos , Physalis , Vitanolídeos , Humanos , Physalis/química , Transportador de Glucose Tipo 1 , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Proteínas Facilitadoras de Transporte de Glucose , Extratos Vegetais/química , Vitanolídeos/farmacologia , Vitanolídeos/química , Proteínas de Membrana Transportadoras , Estrutura Molecular
14.
Sci Total Environ ; 912: 169371, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38104809

RESUMO

The constraint of phosphorus (P) fixation on crop production in alkaline calcareous soils can be alleviated by applying bioinoculants. However, the impact of bacterial inoculants on this process remains inadequately understood. Here, a field study was conducted to investigate the effect of a high-concentration, cost-effective, and slow-release granular bacterial inoculant (GBI) on maize (Zea mays L.) plant growth. Additionally, we explored the effects of GBI on rhizosphere soil aggregate physicochemical properties, rhizosphere soil P fraction, and microbial communities within aggregates. The outcomes showed a considerable improvement in plant growth and P uptake upon application of the GBI. The application of GBI significantly enhanced the AP, phoD gene abundance, alkaline phosphatase activity, inorganic P fractions, and organic P fractions in large macroaggregates. Furthermore, GBI impacted soil aggregate fractionation, leading to substantial alterations in the composition of fungal and bacterial communities. Notably, key microbial taxa involved in P-cycling, such as Saccharimonadales and Mortierella, exhibited enrichment in the rhizosphere soil of plants treated with GBI. Overall, our study provides valuable insight into the impact of GBI application on microbial distributions and P fractions within aggregates of alkaline calcareous soils, crucial for fostering healthy root development and optimal crop growth potential. Subsequent research endeavors should delve into exploring the effects of diverse GBIs and specific aggregate types on P fraction and community composition across various soil profiles.


Assuntos
Inoculantes Agrícolas , Microbiota , Solo/química , Zea mays , Rizosfera , Fósforo , Microbiologia do Solo
15.
J Agric Food Chem ; 72(1): 715-725, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123485

RESUMO

Cd pollution-safe cultivar (Cd-PSC) is a feasible strategy to minimize Cd contamination in leafy vegetables. The shoot Cd concentrations of 23 Lactuca sativa cultivars under Cd stress ranged from 0.124 to 2.155 mg·kg-1 with a maximum cultivar difference of 8 folds. Typical Cd-PSC C16 (L) and high-Cd-accumulating cultivar C13 (H) were screened to investigate the mechanisms of Cd accumulations in L. sativa through determining Cd concentrations, Cd subcellular distributions, phytochelatin profiles, and phytochelatin biosynthesis-related genes' expressions. Higher Cd distribution in a heat stable fraction in C13 (H) indicated that the high Cd accumulation trait of C13 (H) mainly depended on the Cd-phytochelatin complexes. Root phytochelatin concentrations were significantly elevated in C13 (H) (5.83 folds) than in C16 (L) (2.69 folds) (p < 0.05) under Cd stress. Significantly downregulated expressions of glutathione S-transferase rather than the regulation of phytochelatin synthesis genes in the root of C13 (H) might be responsible for sufficient glutathione supply for phytochelatins synthesis. These findings suggested that phytochelatin elevation in C13 (H) would favor the Cd root to shoot transportation, which provides new insights into the phytochelatin-related cultivar-dependent Cd accumulating characteristic in L. sativa.


Assuntos
Fitoquelatinas , Poluentes do Solo , Fitoquelatinas/metabolismo , Cádmio/metabolismo , Lactuca/genética , Poluentes do Solo/metabolismo , Raízes de Plantas/química
16.
Phytochemistry ; 217: 113912, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37918620

RESUMO

Artemisia argyi Levl. Et Vant, commonly known as "Chinese Mugwort," has been utilized in traditional Chinese medicine and cuisine for centuries. Aged Chinese Mugwort has been uncovered to possess superior quality and safety, and its ethyl acetate extract has been found to exhibit anti-hepatitis B virus (HBV) activity. In this study, twenty-five sesquiterpenoids were isolated and characterized from three-year-aged A. argyi. Among them, 14 previously undescribed sesquiterpenoids (1-14), featuring double bond oxidation or ring opening. It is hypothesized that during the aging process, sesquiterpenes undergo oxidative transformation of their double bonds to form alcohols due to external factors and inherent properties. The anti-HBV activity and cytotoxicity of all compounds were assessed in vitro using HepG 2.2.15 cells, and their structure-activity relationships were analyzed through three-dimensional quantitative structure-activity relationship (3D-QASR) techniques. The α-methylene-γ-lactone sesquiterpenoid derivatives were discovered to have potent inhibitory activity against HBV. This research may broaden the potential applications of Chinese Mugwort and offer further guidance for its development and utilization as functional food or traditional Chinese medicine.


Assuntos
Artemisia , Sesquiterpenos , Vírus da Hepatite B , Relação Quantitativa Estrutura-Atividade , Artemisia/química , Medicina Tradicional Chinesa , Sesquiterpenos/farmacologia
17.
Plant Physiol Biochem ; 206: 108199, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38100890

RESUMO

Cadmium (Cd) contamination is a serious challenge in agricultural soils worldwide, resulting in Cd entering the food chain mainly through plant-based food and threatening human health. Minimizing Cd bioaccumulation in wheat is an important way to prevent Cd hazards to humans. Hydroponic and pot experiments were conducted to comprehensively evaluate the effects of zinc sulfate (ZnSO4) and zinc oxide nanoparticles (nZnO) on Cd uptake, translocation, subcellular distribution, cellular ultrastructure, and gene expression in two wheat genotypes that differ in grain Zn accumulation. Results showed that high-dose nZnO significantly reduced root Cd concentration (52.44%∼56.85%) in two wheats, in contrast to ZnSO4. The S216 exhibited higher tolerance to Cd compared to Z797. Importantly, Zn supplementation enhanced Cd sequestration into vacuoles and binding to cell walls, which conferred stability to ultracellular structures and photosynthetic apparatus. Down-regulation of influx transporter (TaHMA2 and TaLCT1) and up-regulation of efflux transporters (TaTM20 and TaHMA3) in Z797 might contribute to Zn-dependent alleviation of Cd toxicity and enhance its Cd tolerance. Down-regulation of ZIP transporters (TaZIP3, -5, and -7) might contribute to an increase in root Zn concentration and inhibit Cd absorption. Additionally, soil Zn provided an effective strategy for the reduction of grain Cd concentrations in both wheats, with a reduction of 26%∼32% (high ZnSO4) and 11%∼67% (high nZnO), respectively. Collectively, these findings provide new insights and perspectives on the mechanisms of Cd mitigation in wheats with different Zn fertilizers and demonstrate that the effect of nZnO in mitigating Cd stress is greater than that of ZnSO4 fertilizers.


Assuntos
Nanopartículas , Poluentes do Solo , Óxido de Zinco , Humanos , Óxido de Zinco/farmacologia , Cádmio/metabolismo , Zinco/farmacologia , Zinco/metabolismo , Triticum/metabolismo , Fertilizantes , Solo , Proteínas de Membrana Transportadoras/metabolismo , Expressão Gênica , Poluentes do Solo/metabolismo
18.
BMC Plant Biol ; 23(1): 638, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38072959

RESUMO

BACKGROUND: Six-spotted spider mite (Eotetranychus sexmaculatus) is one of the most damaging pests of tea (Camellia sinensis). E. sexmaculatus causes great economic loss and affects tea quality adversely. In response to pests, such as spider mites, tea plants have evolved resistance mechanisms, such as expression of defense-related genes and defense-related metabolites. RESULTS: To evaluate the biochemical and molecular mechanisms of resistance in C. sinensis against spider mites, "Tianfu-5" (resistant to E. sexmaculatus) and "Fuding Dabai" (susceptible to E. sexmaculatus) were inoculated with spider mites. Transcriptomics and metabolomics based on RNA-Seq and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) technology were used to analyze changes in gene expression and metabolite content, respectively. RNA-Seq data analysis revealed that 246 to 3,986 differentially expressed genes (DEGs) were identified in multiple compared groups, and these DEGs were significantly enriched in various pathways, such as phenylpropanoid and flavonoid biosynthesis, plant-pathogen interactions, MAPK signaling, and plant hormone signaling. Additionally, the metabolome data detected 2,220 metabolites, with 194 to 260 differentially abundant metabolites (DAMs) identified in multiple compared groups, including phenylalanine, lignin, salicylic acid, and jasmonic acid. The combined analysis of RNA-Seq and metabolomic data indicated that phenylpropanoid and flavonoid biosynthesis, MAPK signaling, and Ca2+-mediated PR-1 signaling pathways may contribute to spider mite resistance. CONCLUSIONS: Our findings provide insights for identifying insect-induced genes and metabolites and form a basis for studies on mechanisms of host defense against spider mites in C. sinensis. The candidate genes and metabolites identified will be a valuable resource for tea breeding in response to biotic stress.


Assuntos
Camellia sinensis , Tetranychidae , Animais , Camellia sinensis/genética , Camellia sinensis/metabolismo , Tetranychidae/genética , Cromatografia Líquida , Espectrometria de Massas em Tandem , Melhoramento Vegetal , Perfilação da Expressão Gênica , Transcriptoma , Redes e Vias Metabólicas , Chá/metabolismo , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas , Folhas de Planta/metabolismo , Proteínas de Plantas/genética
19.
Technol Health Care ; 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38073348

RESUMO

BACKGROUND: Malnutrition is a widespread problem in critically ill patients with neurological disorders. OBJECTIVE: The purpose of this study is to investigate the effect of a multidisciplinary collaborative nutritional treatment mode based on a standardized unit for nutritional support on the outcome metrics in patients with neurological disorders who are critically ill. METHODS: We enrolled 84 participants who were hospitalized in the intensive care unit (ICU) of Yancheng No. 1 People's Hospital for neurological disorders between June 2018 and December 2021. The participants were randomly assigned to the control group and the test group. The control group received traditional nutritional support, while the test group was treated with a multidisciplinary collaborative nutritional treatment mode based on a standardized unit for nutritional support. We collected the general information, feeding tolerance (FT), nutritional risk score, and laboratory indicators before intervention, after intervention for one week, and after intervention for 2 weeks, and other data of the participants. RESULTS: After the intervention, the test group scored significantly lower than the control group in the incidence of gastroparesis and diarrhea, as well as the NUTRIC score, with statistically significant differences (P< 0.001). The prealbumin levels in the test group increased progressively prior to intervention, after intervention for one week, and after intervention for two weeks. Compared to the control group, the test group had higher prealbumin levels prior to intervention, after intervention for one week, and after intervention for two weeks, with statistically significant differences (P< 0.001). CONCLUSION: We developed a multidisciplinary collaborative nutritional treatment model based on a standard unit for nutritional support. This model can improve neural function, FT, and pertinent outcome indicators and is generally applicable.

20.
Front Med (Lausanne) ; 10: 1294421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089867

RESUMO

Asthma, a chronic respiratory ailment, affects millions worldwide. Extracorporeal membrane oxygenation (ECMO) has gained traction as a life-saving intervention for patients with severe asthma who are unresponsive to conventional treatments. However, complications associated with ECMO, including electrolyte imbalances and hemorrhage, can have significant clinical implications. This case report highlights a 49 years-old male patient with severe asthma who developed pronounced hypokalemia and hemorrhage following venovenous ECMO (VVECMO) therapy. Despite potassium supplementation, serum potassium levels continued declining before normalizing after 24 h. The patient subsequently experienced gastrointestinal bleeding, cerebral hemorrhage, and extensive cerebral infarction, ultimately resulting in a deep coma. Hypokalemia during ECMO therapy can result from a rapid reduction of carbon dioxide, ß-receptor agonist use, corticosteroid use, and diuretic administration. Hemorrhage is another common ECMO complication, often linked to heparin anticoagulation therapy. Clinicians should be aware of potential complications and adopt appropriate prevention and management strategies when using ECMO in patients with severe asthma.

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