Extracellular vesicles in endometriosis: role and potential.

Endometriosis is a chronic inflammatory gynecological disease, which profoundly jeopardizes women's quality of life and places a significant medical burden on society. The pathogenesis of endometriosis remains unclear, posing major clinical challenges in diagnosis and treatment. There is an urgent demand for the development of innovative non-invasive diagnostic techniques and the identification of therapeutic targets. Extracellular vesicles, recognized for transporting a diverse array of signaling molecules, have garnered extensive attention as a novel mode of intercellular communication. A burgeoning body of research indicates that extracellular vesicles play a pivotal role in the pathogenesis of endometriosis, which may provide possibility and prospect for both diagnosis and treatment. In light of this context, this article focuses on the involvement of extracellular vesicles in the pathogenesis of endometriosis, which deliver information among endometrial stromal cells, macrophages, mesenchymal stem cells, and other cells, and explores their potential applications in the diagnosis and treatment, conducing to the emergence of new strategies for clinical diagnosis and treatment.

CDK-independent role of D-type cyclins in regulating DNA mismatch repair.

Although mismatch repair (MMR) is essential for correcting DNA replication errors, it can also recognize other lesions, such as oxidized bases. In G0 and G1, MMR is kept in check through unknown mechanisms as it is error-prone during these cell cycle phases. We show that in mammalian cells, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. D-type cyclins inhibit the proteasomal degradation of p21, which competes with MMR proteins for binding to PCNA, thereby inhibiting MMR. The ability of D-type cyclins to limit MMR is CDK4- and CDK6-independent and is conserved in G0 and G1. At the G1/S transition, the timely, cullin-RING ubiquitin ligase (CRL)-dependent degradation of D-type cyclins and p21 enables MMR activity to efficiently repair DNA replication errors. Persistent expression of D-type cyclins during S-phase inhibits the binding of MMR proteins to PCNA, increases the mutational burden, and promotes microsatellite instability.

D-type cyclins regulate DNA mismatch repair in the G1 and S phases of the cell cycle, maintaining genome stability.

The large majority of oxidative DNA lesions occurring in the G1 phase of the cell cycle are repaired by base excision repair (BER) rather than mismatch repair (MMR) to avoid long resections that can lead to genomic instability and cell death. However, the molecular mechanisms dictating pathway choice between MMR and BER have remained unknown. Here, we show that, during G1, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. D-type cyclins shield p21 from its two ubiquitin ligases CRL1SKP2 and CRL4CDT2 in a CDK4/6-independent manner. In turn, p21 competes through its PCNA-interacting protein degron with MMR components for their binding to PCNA. This inhibits MMR while not affecting BER. At the G1/S transition, the CRL4AMBRA1-dependent degradation of D-type cyclins renders p21 susceptible to proteolysis. These timely degradation events allow the proper binding of MMR proteins to PCNA, enabling the repair of DNA replication errors. Persistent expression of cyclin D1 during S-phase increases the mutational burden and promotes microsatellite instability. Thus, the expression of D-type cyclins inhibits MMR in G1, whereas their degradation is necessary for proper MMR function in S.

[Comprehensive identification of metabolites and metabolic characteristics of luteolin and kaempferol in Simiao Yong'an Decoction in rats by UHPLC-LTQ-Orbitrap MS/MS].

Simiao Yong'an Decoction is a classic prescription for treating gangrene. Modern medical evidence has proven that Si-miao Yong'an Decoction has therapeutic effects on atherosclerosis(AS), vascular occlusion angeitides, and hypertension, while its pharmacodynamic mechanism remains unclear. The evidence of network pharmacology, molecular docking, literature review, and our previous study suggests that luteolin and kaempferol are two major flavonoids in Simiao Yong'an Decoction and can inhibit macrophage inflammation and exert anti-AS effects. However, due to lack of the metabolism studies in vivo, little is known about the metabolic characteristics of luteolin and kaempferol. This study employed ultra-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS/MS) and relevant software to identify the metabolites and metabolic pathways of luteolin and kaempferol in rat plasma, urine, and feces, after oral administration of luteolin and kaempferol, respectively. After the administration of luteolin, 10, 11, and 3 metabolites of luteolin were detected in the plasma, urine, and feces, respectively. After the administration of kaempferol, 9, 3, and 1 metabolites of kaempferol were detected in the plasma, urine, and feces, respectively. The metabolic pathways mainly involved methylation, glucuronidation, and sulfation. This study enriches the knowledge about the pharmacological mechanism of luteolin and kaempferol and supplies a reference for revealing the metabolic process of other flavonoids in Simiao Yong'an Decoction, which is of great significance for elucidating the pharmacological effects and effective substances of this decoction in vivo.

Effects of Noni (Morinda citrifolia L.) Fruit Extract Supplemented in Cashmere Goats with a High-Concentrate Diet on Growth Performance, Ruminal and Colonic Fermentation and SARA.

This experiment was conducted to investigate the effects of noni fruit extract (NFE) on growth performance, ruminal and colonic fermentation, nutrient digestion, and subacute rumen acidosis (SARA) of cashmere goats with the high-concentrate diet. Twenty-four cashmere kids (17.9 ± 1.45 kg of BW ± SD) were randomly assigned to three treatments: low-concentrate diet, high-concentrate (HC) diet, or HC diet supplemented with NFE at 1 g per kg DM (0.1%). The results showed that although the HC diet improved the average daily gain (ADG) and feed conversion rate (FCR), it was accompanied by SARA with a decreased pH and an increased lactic acid of both rumen and colon, and decreased digestibility of neutral detergent fiber (NDF)and acid detergent fiber (ADF). The supplementation of 0.10% NFE in the HC diet could not only effectively alleviate SARA symptoms and colon fermentation disorders, such as reversing the decrease of pH and alleviating the increase of lactic acid in rumen and colon, but also mitigate the decline of fiber digestibility caused by long-term feeding in the HC diet, and increase the digestibility of crude protein(CP) and dry matter (DM), which improved the ADG and FCR of cashmere kids. Thus, NFE provides new strategies for alleviating SARA and promoting cashmere goat growth.

Coronary computed tomography angiography analysis using artificial intelligence for stenosis quantification and stent segmentation: a multicenter study.

Background: Accurate interpretation of coronary computed tomography angiography (CCTA) is a labor-intensive and expertise-driven endeavor, as inexperienced readers may inadvertently overestimate stenosis severity. Recent artificial intelligence (AI) advances in medical imaging present compelling prospects for auxiliary diagnostic tools in CCTA. This study aimed to externally validate an AI-assisted analysis system capable of rapidly evaluating stenosis severity, exploring its potential integration into routine clinical workflows. Methods: This multicenter study consisted of an internal and external cohort of patients who underwent CCTA scans between April 2017 and February 2023. CCTA scans were evaluated using Coronary Artery Disease Reporting and Data System (CAD-RADS) scores to determine stenosis severity, while ground-truth stents were manually annotated by expert readers. The InferRead CT Heart (version 1.6; Infervision Medical Technology Co., Ltd., Beijing, China), which incorporates AI-assisted coronary artery stenosis quantification and automatic stent segmentation, was employed for CCTA scan analysis. AI-based stenosis assessment performance was determined using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), while the AI-based stent segmentation overlap was assessed using the Dice similarity coefficient (DSC). Results: For ≥50% stenosis diagnoses, the AI system attained per-patient sensitivity, specificity, PPV, and NPV surpassing 90.0% for the internal dataset; for the external dataset, the per-patient values were 88.0% [95% confidence interval (CI): 81.0-94.4%], 94.5% (95% CI: 90.7-97.6%), 90.0% (95% CI: 83.3-95.6%), and 93.4% (95% CI: 89.2-96.8%), respectively. For ≥70% stenosis diagnoses, the per-patient values on the internal dataset were 94.2% (95% CI: 89.2-98.1%), 95.8% (95% CI: 94.1-97.4%), 80.8% (95% CI: 73.5-87.7%), and 98.9% (95% CI: 97.9-99.6%), respectively; for the external dataset, the per-patient values were 91.9% (95% CI: 82.6-100.0%), 97.3% (95% CI: 94.9-99.1%), 85.0% (95% CI: 72.5-94.6%), and 98.6% (95% CI: 96.8-100.0%), respectively. Regarding CAD-RADS categorization, the Cohen kappa was 0.75 and 0.81 for the internal per-patient and per-vessel basis, respectively, and 0.72 and 0.76 for the external per-patient and per-vessel basis, respectively. The DSC for stent segmentation was 0.96±0.06. Conclusions: The AI-assisted analysis system for CCTA interpretation exhibited exceptional proficiency in stenosis quantification and stent segmentation, indicating that AI holds considerable potential in advancing CCTA postprocessing techniques.

A noncanonical function of SKP1 regulates the switch between autophagy and unconventional secretion.

Intracellular degradation of proteins and organelles by the autophagy-lysosome system is essential for cellular quality control and energy homeostasis. Besides degradation, endolysosomal organelles can fuse with the plasma membrane and contribute to unconventional secretion. Here, we identify a function for mammalian SKP1 in endolysosomes that is independent of its established role as an essential component of the family of SCF/CRL1 ubiquitin ligases. We found that, under nutrient-poor conditions, SKP1 is phosphorylated on Thr131, allowing its interaction with V1 subunits of the vacuolar ATPase (V-ATPase). This event, in turn, promotes V-ATPase assembly to acidify late endosomes and enhance endolysosomal degradation. Under nutrient-rich conditions, SUMOylation of phosphorylated SKP1 allows its binding to and dephosphorylation by the PPM1B phosphatase. Dephosphorylated SKP1 interacts with SEC22B to promote unconventional secretion of the content of less acidified hybrid endosomal/autophagic compartments. Collectively, our study implicates SKP1 phosphorylation as a switch between autophagy and unconventional secretion in a manner dependent on cellular nutrient status.

The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication.

IMPORTANCE: Generation of virus-host protein-protein interactions (PPIs) maps may provide clues to uncover SARS-CoV-2-hijacked cellular processes. However, these PPIs maps were created by expressing each viral protein singularly, which does not reflect the life situation in which certain viral proteins synergistically interact with host proteins. Our results reveal the host-viral protein-protein interactome of SARS-CoV-2 NSP3, NSP4, and NSP6 expressed individually or in combination. Furthermore, REEP5/TRAM1 complex interacts with NSP3 at ROs and promotes viral replication. The significance of our research is identifying virus-host interactions that may be targeted for therapeutic intervention.

Current status and influencing factors of participating satisfaction during surgical treatment decision-making among breast cancer patients with immediate breast reconstruction.

OBJECTIVE: Breast reconstruction (BR) is a positive contribution to aesthetic effect among breast cancer patients. Identification of influenced factors for participating satisfaction may provide insights on the decision-making theory to promote patient's autonomy in surgical choice. The purpose of this study was to examine the level of participating satisfaction with surgical treatment decision-making and its predictors among breast cancer patients with immediate BR. METHODS: A cross-sectional study was conducted including 163 breast cancer patients with immediate BR in Mainland China. Data was collected using patients' participation satisfaction in medical decision-making scale (PSMDS), Big five Short-Form (BFI) Scale, Patient Participation Competence Scale(PPCS) and Patients' Preference (MPP) scale. Descriptive, bivariate, and multivariate regression analyses were used. RESULTS: Scores of PSMD were 86.38 ± 15.74. Multiple regression analyses indicated autonomous decision-making, marital statue, information acquisition competence, agreeableness, and decision-making preferences as indicators, explaining 29.6% of the response variation (P < 0.05). CONCLUSIONS: The level of PSMD in breast cancer patients with immediate BR need to be improved. Patients with greater autonomous decision-making, married, higher information acquisition competence, agreeableness, and collaborative role are more likely to have an preferable PSMD. A comprehensive assessment and effective decision-making support are needed initially for BC patients to promote positive participation when making surgical decision.

H3K79 methylation promotes rapid growth of Alexandrium pacificum under high light intensity via increased photosynthesis.

Alexandrium pacificum is one of the main species responsible for harmful algal blooms, posing serious threats to coastal ecosystems, economies, and public health. Light intensity is an important abiotic factor affecting the occurrence of red tides. In a certain range, increasing light intensity can promote the rapid growth of A. pacificum. This study aimed to elucidate the molecular mechanisms of H3K79 methylation (H3K79me) in response to high light intensity during the rapid growth of A. pacificum and the formation of toxic red tides. The research found that the abundance of H3K79me increased 2.1-fold under high light (HL, 60 µmol photon m-2 s-l) compared to control light conditions (CT, 30 µmol photon m-2 s-l), which was consistent with the trend of rapid growth under HL, and both can be inhibited by EPZ5676. Then effector genes of H3K79me under HL were identified using ChIP-seq and a virtual genome constructed based on transcriptome data of A. pacificum for the first time. The results showed that the differential modification-associated genes were primarily enriched in the pathways of "energy metabolism", "carbon metabolism", and "amino acid metabolism". These findings were confirmed through ChIP-qPCR. Subsequently, H3K79me-associated genes CP43 and GOGAT were identified by combined analysis of ChIP-seq and differentially expressed genes. Finally, pharmacological experiments using the H3K79me inhibitor EPZ5676 showed that the expression of the photosynthesis-related gene CP43 was significantly reduced by 2.5-fold and the maximum photochemical quantum efficiency of A. pacificum was reduced by 1.2 to 1.8-fold in HL compared with CT, leading to inhibited growth of A. pacificum. These results suggest that H3K79me plays a role in regulating the rapid growth of A. pacificum and photosynthesis is likely an important regulatory pathway, which is the first to provide epigenetic evidence underlying the formation of toxic red tides from the perspective of H3K79me.

Mechanism of Al toxicity alleviation in acidic red soil by rice-straw hydrochar application and comparison with pyrochar.

In the past decade, biochar has been widely regarded as a new type of soil conditioner that can effectively control soil acidification and alleviate Al toxicity. Hydrochar is identified as a more economical carbon material than pyrochar, but its effect on Al toxicity and the associated mechanism have not been studied. Thus, a two-stage indoor incubation experiment was conducted to investigate the effect of rice-straw hydrochar (HC, application rate: 1/2/3 %) on maize seedling root growth, soil solution Al activity, soil exchangeable Al and pH buffering ability in acidic red soils from two sites. We also used pyrochar (PC, application rate: 3 %) produced from the same rice straw for comparison. Except for HC-1 %, both hydrochar and pyrochar addition significantly stimulated relative root elongation (136.36 % ~ 284.09 %), diminished the cell death ratio (27.96 % ~ 85.56 %) and Al content in root tips (18.80 % ~ 80.11 %) by decreasing the total Al content (44.78 % ~ 76.10 %) and the proportion of Al3+ species (27 % ~ 32 %) in soil solution. Hydrochar did not significantly promote the soil pH buffer capacity (pH-BC) or effective cation exchange capacity (ECEC), while PC-3 % did. The DOC (dissolved organic carbon) content of soil solution was dramatically elevated by 203.9 % ~ 783.2 % after hydrochar addition. Hydrochar mitigates Al activity in soil solution mainly through Al-DOC complexation and adsorption, thus suppressing the Al toxicity of maize roots. Hydrochar may be an economical soil amendment for ameliorating Al toxicity despite its overall alleviation effect on Al toxicity being lower than pyrochar.

Characterizations for the photothermal effect of Rhodamine 6G using white-light interferometry and windowed Fourier transform.

Photothermal phenomenon is one of the natural responses in light-matter interactions in which the energy of the incident light is converted into heat, resulting in a temperature increase in the illuminated material. This effect has a direct influence on the refractive index of the material such that its change of spectral dependency with temperature can be exploited for different applications. However, it is also important to separate/identify the thermal effect from the optical/electronic resonance effect to expand potential applications of light-matter interactions. In this work, we demonstrate the use of a white-light interferometry approach combined with a windowed Fourier transform method and a consistency-checking peak-fitting method to obtain the refractive index of an Rh6G-ethanol dye solution with a sensitivity of about ∼10-6 (RIU) for the visible range. Moreover, we also perform both static and dynamic measurements to study the photothermal effect of the Rh6G solution under external excitation. Importantly, we separate the optical and thermal effects due to the external excitation and obtain very good agreement with the experimental results by modeling the relative refractive index of the Rh6G solution with an expression consisting of spectrally a Fano-like resonance term and a linear dependent thermal term. We find that the response due to the optical effect is about ∼0.2 × 10-3 of that due to the thermal effect in the low-light regime. Our approach to separating the optical and thermal effects could shed light on other fields for potential applications through precision measurements of the transmission phase or refractive index.

Dietary Polysaccharide-Rich Extract from Noni (Morinda citrifolia L.) Fruit Modified Ruminal Fermentation, Ruminal Bacterial Community and Nutrient Digestion in Cashmere Goats.

In two consecutive studies, we evaluated the effects of polysaccharide-rich noni (Morinda citrifolia L.) fruit extract (NFP) on ruminal fermentation, ruminal microbes and nutrient digestion in cashmere goats. In Exp. 1, the effects of a diet containing NFP of 0, 0.1%, 0.2%, 0.4% and 0.55% on in vitro ruminal fermentation at 3, 6, 9, 12 and 24 h were determined, whereas in Exp. 2, fourteen cashmere goats (46.65 ± 3.36 kg of BW ± SD) were randomly assigned to two treatments: the basal diet with or without (CON) supplementation of NFP at 4 g per kg DM (0.4%). The in vitro results showed that NFP linearly increased concentrations of volatile fatty acids (VFA), quadratically decreased ammonia-N concentration, and changed pH, protozoa number, gas production and the microbial protein (MCP) concentration, and was more effective at 0.4% addition, which yielded similar results in ruminal fermentation in Exp. 2. In addition, NFP increased the apparent digestibility of dry matter and crude protein and the abundance of Firmicutes, and reduced the abundance of Bacteroides and Actinobacteria. Ruminococcus_1 was positively associated with VFA concentration. The Rikenellaceae_RC9_gut_group was positively correlated with protozoa and negatively correlated with MCP concentration. Thus, NFP has potential as a ruminal fermentation enhancer for cashmere goats.

Visualizing Single-Stranded DNA Foci in the G1 Phase of the Cell Cycle.

DNA has dedicated cellular repair pathways capable of coping with lesions that could arise from both endogenous and/or exogenous sources. DNA repair necessitates collaboration between numerous proteins, responsible for covering a broad range of tasks from recognizing and signaling the presence of a DNA lesion to physically repairing it. During this process, tracks of single-stranded DNA (ssDNA) are often created, which are eventually filled by DNA polymerases. The nature of these ssDNA tracks (in terms of both length and number), along with the polymerase recruited to fill these gaps, are repair pathway-specific. The visualization of these ssDNA tracks can help us understand the complicated dynamics of DNA repair mechanisms. This protocol provides a detailed method for the preparation of G1 synchronized cells to measure ssDNA foci formation upon genotoxic stress. Using an easy-to-utilize immunofluorescence approach, we visualize ssDNA by staining for RPA2, a component of the heterotrimeric replication protein A complex (RPA). RPA2 binds to and stabilizes ssDNA intermediates that arise upon genotoxic stress or replication to control DNA repair and DNA damage checkpoint activation. 5-Ethynyl-2'-deoxyuridine (EdU) staining is used to visualize DNA replication to exclude any S phase cells. This protocol provides an alternative approach to the conventional, non-denaturing 5-bromo-2'-deoxyuridine (BrdU)-based assays and is better suited for the detection of ssDNA foci outside the S phase.

Super-Excimer: Anomalous Bonding in a Metastable Excited-State Dimer of Superatomic Dimers.

A new type of excimer formation was reported, which stems from an unexpected discovery of a short-lived excited-state dimer of superatomic dimers. In theoretical investigation of the dimer formation, it was found that the physical adsorption states maintain the closed-shell properties of the dimeric units via van der Waals interaction, while the chemical adsorption excited state is a broken-symmetry (BS) state, having a higher energy of about 0.5 eV. Potential energy surface calculations indicate that the short-lived metastable chemical bonding state can transform into energetically lower physical adsorption states by crossing a shallow energy barrier and eventually disintegrate into two ground-state dimers. Since the basic unit is a superatomic cluster, the chemical adsorption state discovered may be called "super-excimer", which opens up a new avenue for the discovery of tailorable excimer materials.

The effects of supplementation of noni (Morinda citrifolia L.) fruit polysaccharides-rich extract on antioxidant status and immune function in cashmere goats.

This experiment was designed to examine the effects of a dietary supplementation of polysaccharides-rich noni (Morinda citrifolia L.) fruit extract (NFP) on the anti-oxidant enzyme activities, cytokines level, and expression of corresponding genes in blood of cashmere goats. Twelve castrated, 2-yr-old male cashmere goats (45.44 ± 3.30 kg of BW ± SD) were used in a 2 × 2 crossover design: the basal diet with or without (CON) supplementation of NFP at 4 g per kg DM (0.4%). Each period lasted for 29 d, including 1 wk for diet transition, 20 d for adaptation, and the last 2 d for sampling. The results showed that NFP supplementation increased (P < 0.05) the levels of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and the activities of catalase (CAT), glutathione peroxidase (GPx), thioredoxin reductase (TrxR), and total superoxide dismutase (T-SOD) in serum. The expressions of CAT, GPx4, TrxR, SOD1, IL-6, and TNF-α genes were upregulated (P < 0.05), whereas the levels of malondialdehyde (P = 0.015) and reactive oxygen species (P = 0.051) in serum were reduced. The body weight gain of goats was increased (P = 0.006) with a nonsignificant increase of feed intake with NFP supplementation. In conclusion, dietary NFP supplementation enhanced the antioxidant status and immune function in blood of cashmere goats.

Due to the limited pasture supply and the seasonal imbalance of nutrients in grazed pastures in China, cashmere goats are commonly raised in a confined yard-feeding system, which may result in oxidative stress from a lack of green pastures. Noni (Morinda citrifolia L.) fruit polysaccharides contain various biological compounds that function as anti-inflammatory, antitumor, and to enhance immune responses, hence likely to relieve oxidative stress in animals. Previous researches in our laboratory have shown that polysaccharides-rich extract from noni fruit (NFP) enhanced rumen fermentation in cashmere goats. This experiment was designed to evaluate the effect of NFP supplementation on serum antioxidant status and immune function in cashmere goats. The results showed that dietary supplementation of 0.40% NFP enhanced the immune signaling molecule levels and antioxidant enzyme activities by upregulating the expression of related genes in blood and reduced the levels of lipid peroxides and free radicals in serum, while mature goats improved body weight. Therefore, NFP could be a viable source of antioxidants for cashmere goats.

Resveratrol Attenuates Heat Stress-Induced Impairment of Meat Quality in Broilers by Regulating the Nrf2 Signaling Pathway.

Studies have indicated that dietary resveratrol (RES) improves the meat quality of broilers subjected to heat stress (HS), but the mechanism of action remains unclear. Therefore, the main purpose of this study was to investigate the effect of RES on meat quality, muscle antioxidant status, and its mechanism of action in broilers under HS. A total of 162 male AA broilers at 21 days old with similar weight were randomly assigned to 3 treatment groups with 6 replicates each. The control group (ambient temperature: 22 ± 1 °C) and HS group (ambient temperature: 33 ± 1 °C for 10 h a day from 8:00 to 18:00 and 22 ± 1 °C for the remaining time) were fed a basal diet and the HS + RES group was fed a basal diet with 400 mg/kg RES. The feeding was conducted for 21 continuous days. The results indicated that HS decreased final body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), breast and leg muscle yield, a*24h, pH24h, the activities of catalase (CAT), glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px), and mRNA levels of nuclear factor erythroid 2−related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1), and GSH-Px (p < 0.05). HS also increased b*45min, L*24h, drip loss, malondialdehyde (MDA) content, and kelch-like epichlorohydrin-associated protein 1 (Keap1) mRNA level (p < 0.05). Compared with the HS group, the HS + RES group exhibited a higher ADG, breast and leg muscle yield, a*24h, pH24h, activities of GST and GSH-Px, and mRNA levels of Nrf2, HO-1, and NQO1 but had lower drip loss and Keap1 mRNA level (p < 0.05). RES can improve meat quality and the muscle antioxidant ability of heat-stressed broilers by activating the Nrf2 signaling pathway.

Comparative Pharmacokinetics of Seven Major Compounds in Normal and Atherosclerosis Mice after Oral Administration of Simiao Yong'an Decoction.

Simiao Yong'an decoction (SMYAD), a classic traditional Chinese medicine formula, has been used to treat atherosclerosis (AS) in clinical in China, but its therapeutic mechanism and pharmacodynamic material basis are not clear. In this study, the AS model was caused by a high-fat diet and perivascular carotid collar placement (PCCP), and SMYAD was orally administered to the model and normal mice. A rapid, sensitive, selective, and reliable method using ultrahigh-performance liquid chromatography (UHPLC) system combined with a Q Exactive HF-X mass spectrometer (UHPLC-Q Exactive HF-X MS) was established and validated for the simultaneous determination of seven compounds, including harpagide, chlorogenic acid, swertiamarin, sweroside, angoroside C, liquiritin, and isoliquiritigenin in the plasma of normal and AS mice. The specificity, linearity, precision, accuracy, recovery, and stability of the method were all within the acceptable criteria. The results showed that some pharmacokinetic behaviors of harpagide, chlorogenic acid, and isoliquiritigenin were significantly different among the two groups of mice. The specific parameter changes were harpagide (AUC0-t and AUC0-∞ were 11075.09 ± 2132.38 and 16221.95 ± 5622.42 ng·mL-1·h, respectively; CLz/F was 2.45 ± 0.87 L/h/mg), chlorogenic acid (t 1/2 was 21.59 ± 9.16 h; AUC0-∞ was 2637.51 ± 322.54 ng·mL-1·h; CLz/F was 13.49 ± 1.81 L/h/mg) and isoliquiritigenin (AUC0-t and AUC0-∞ were 502.25 ± 165.65 and 653.68 ± 251.34 ng·mL-1·h, respectively; CLz/F was 62.16 ± 23.35 L/h/mg) were altered under the pathological status of AS. These differences might be partly ascribed to the changes in gastrointestinal microbiota, nonspecific drug transporters, and cytochrome P450 activity under the AS state, providing research ideas and experimental basis for pharmacological effects and pharmacodynamic material basis.

Dietary Chitosan Supplementation Improved Egg Production and Antioxidative Function in Laying Breeders.

This study was conducted to explore the dietary effect of chitosan on the production performance, and antioxidative enzyme activities and corresponding gene expression in the liver and duodenum of laying breeders. A total of 450 laying breeders (92.44% ± 0.030% of hen-day egg production) were randomly assigned to five dietary treatments fed 8 weeks: maize-soybean meal as the basal control diet and the basal diet containing 250, 500, 1000 and 2000 mg/kg of chitosan, respectively. Each treatment was randomly divided into 6 equal replicates, with 15 laying breeders in each replicate. The results showed that dietary chitosan could increase hen-day egg production and feed conversion ratio, especially at the level of 250~500 mg/kg; however, chitosan had no prominent effect on feed intake and average egg weight. Dietary chitosan could dose-dependently promote the antioxidant status in serum, liver and duodenum of layer breeders. It has a better promotion effect at the level of 500 mg/kg; however, the effect was weakened at the level of 2000 mg/kg. Chitosan was likely to enhance the gene expression and activities of Nrf2-mediated phase II detoxification enzyme by up-regulating the expression of Nrf2, thereby improving the antioxidant capacity of laying breeder hens.

Mechanistic Insight into PPARγ and Tregs in Atherosclerotic Immune Inflammation.

Atherosclerosis (AS) is the main pathological cause of acute cardiovascular and cerebrovascular diseases, such as acute myocardial infarction and cerebral apoplexy. As an immune-mediated inflammatory disease, the pathogenesis of AS involves endothelial cell dysfunction, lipid accumulation, foam cell formation, vascular smooth muscle cell (VSMC) migration, and inflammatory factor infiltration. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in lipid metabolism, inflammation, and apoptosis by antagonizing the Wnt/ß-catenin pathway and regulating cholesterol efflux and inflammatory factors. Importantly, PPARγ-dependant fatty acid uptake is critical for metabolic programming. Activated PPARγ can exert an anti-atherosclerotic effect by inhibiting the expression of various inflammatory factors, improving endothelial cell function, and restraining the proliferation and migration of VSMCs. Regulatory T cells (Tregs) are the only subset of T lymphocytes that have a completely negative regulatory effect on the autoimmune response. They play a critical role in suppressing excessive immune responses and inflammatory reactions and widely affect AS-associated foam cell formation, plaque rupture, and other processes. Recent studies have shown that PPARγ activation promotes the recruitment of Tregs to reduce inflammation, thereby exerting its anti-atherosclerotic effect. In this review, we provide an overview of the anti-AS roles of PPARγ and Tregs by discussing their pathological mechanisms from the perspective of AS and immune-mediated inflammation, with a focus on basic research and clinical trials of their efficacies alone or in combination in inhibiting atherosclerotic inflammation. Additionally, we explore new ideas for AS treatment and plaque stabilization and establish a foundation for the development of natural PPARγ agonists with Treg recruitment capability.