Salidroside pretreatment alleviates ferroptosis induced by myocardial ischemia/reperfusion through mitochondrial superoxide-dependent AMPKα2 activation.

BACKGROUND: Ferroptosis, a form of regulated cell death (RCD) that relies on excessive reactive oxygen species (ROS) generation, Fe2+accumulation, abnormal lipid metabolism and is involved in various organ ischemia/reperfusion (I/R) injury, expecially in myocardium. Mitochondria are the powerhouses of eukaryotic cells and essential in regulating multiple RCD. However, the links between mitochondria and ferroptosis are still poorly understood. Salidroside (Sal), a natural phenylpropanoid glycoside isolated from Rhodiola rosea, has mult-bioactivities. However, the effects and mechanism in alleviating ferroptosis caused by myocardial I/R injury remains unclear. PURPOSE: This study aimed to investigate whether pretreated with Sal could protect the myocardium against I/R damage and the underlying mechanisms. In particular, the relationship between Sal pretreatment, AMPKα2 activity, mitochondria and ROS generation was explored. STUDY DESIGN AND METHODS: Firstly, A/R or I/R injury models were employed in H9c2 cells and Sprague-Dawley rats. And then the anti-ferroptotic effects and mechanism of Sal pretreatment was detected using multi-relevant indexes in H9c2 cells. Further, how does Sal pretreatment in AMPKα2 phosphorylation was explored. Finally, these results were validated by I/R injury in rats. RESULTS: Similar to Ferrostatin-1 (a ferroptosis inhibitor) and MitoTEMPO, a mitochondrial free radical scavenger, Sal pretreatment effectively alleviated Fe2+ accumulation, redox disequilibrium and maintained mitochondrial energy production and function in I/R-induced myocardial injury, as demonstrated using multifunctional, enzymatic, and morphological indices. However, these effects were abolished by downregulation of AMPKα2 using an adenovirus, both in vivo and in vitro. Moreover, the results also provided a non-canonical mechanism that, under mild mitochondrial ROS generation, Sal pretreatment upregulated and phosphorylated AMPKα2, which enhanced mitochondrial complex I activity to activate innate adaptive responses and increase cellular tolerance to A/R injury. CONCLUSION: Overall, our work highlighted mitochondria are of great impotance in myocardial I/R-induced ferroptosis and demonstrated that Sal pretreatment activated AMPKα2 against I/R injury, indicating that Sal could become a candidate phytochemical for the treatment of myocardial I/R injury.

Optimized New Shengmai Powder modulation of cAMP/Rap1A signaling pathway attenuates myocardial fibrosis in heart failure.

BACKGROUND: Optimized New Shengmai Powder (ONSMP) is a traditional Chinese medicine formula with significant anti-heart failure and myocardial fibrosis effects, but the specific molecular biological mechanisms are not fully understood. METHODS: In this study, we first used network pharmacology to analyze the ONSMP's active ingredients, core signaling pathways, and core targets. Second, calculate the affinity and binding modes of the ONSMP components to the core targets using molecular docking. Finally, the heart failure rat model was established by ligating the left anterior descending branch of the coronary artery and assessing the effect of ONSMP on myocardial fibrosis in heart failure using echocardiography, cardiac organ coefficients, heart failure markers, and pathological sections after 4 weeks of drug intervention. The cAMP level in rat myocardium was determined using Elisa, the α-SMA and FSP-1 positive expression determined by immunohistochemistry, and the protein and mRNA levels of the cAMP/Rap1A signaling pathway were detected by Western Blotting and quantitative real-time PCR, respectively. RESULTS: The result shows that the possible mechanism of ONSMP in reducing myocardial fibrosis also includes the use of 12 active ingredients such as baicalin, vitamin D, resveratrol, tanshinone IIA, emodin, 15,16-dihydrotanshinone-i to regulate ß1-AR, AC6, EPAC1, Rap1 A, STAT3, and CCND1 on the cAMP/Rap1A signaling pathway, thereby inhibiting the proliferation of cardiac fibroblasts and reduce the excessive secretion of collagen, effectively improve cardiac function and ventricular remodeling in heart failure rats. CONCLUSION: This research shows that ONSMP can inhibit myocardial fibrosis and delay heart failure through the cAMP/Rap1A signaling pathway.

Effect of Glycine on the Wet Carbonation of Steel Slag Used as a Cementitious Material.

The wet carbonation process of steel slag (SS) is envisaged to be an effective way to sequestrate CO2 and improve the properties of SS as a supplementary cementitious material. However, the carbonation process still struggles with having a low carbonation efficiency. This paper studied the effect of glycine on the accelerated carbonation of SS. The phase composition change of carbonated SS was analyzed via XRD, FT-IR, and TG-DTG. The carbonation process of SS is facilitated by the assistance of glycine, with which the carbonation degree is increased. After 60 min of carbonation, SS with glycine obtained a CO2 sequestration rate of 9.42%. Meanwhile, the carbonation reaction could decrease the content of free calcium oxide in SS. This significantly improves the soundness of SS-cement cementitious material, and the compressive strength of cementitious materials that contain carbonated SS with glycine is improved. Additionally, the cycling performance of glycine in the successive wet carbonation process of SS was investigated. Multicycle experiments via solvent recovery demonstrated that although the promotion effect of glycine was reduced after each cycle, compared with the SS-water system, the carbonation process could still be facilitated, demonstrating that successive wet carbonation via solvent recovery has considerable potential. Herein, we provide a new idea to facilitate the wet carbonation process of SS and improve the properties of SS-cement cementitious material.

Isoliquiritin treatment of osteoporosis by promoting osteogenic differentiation and autophagy of bone marrow mesenchymal stem cells.

Osteoporosis is a chronic progressive bone disease characterized by the decreased osteogenic ability of osteoblasts coupled with increased osteoclast activity. Natural products showing promising therapeutic potential for postmenopausal osteoporosis remain underexplored. In this study, we aimed to analyze the therapeutic effects of isoliquiritin (ISL) on osteoporosis in mice and its possible mechanism of action. An ovariectomy-induced osteoporosis mouse model and bone marrow mesenchymal stem cells (BMSCs) were used to analyze the effects of ISL on bone regeneration in vivo and in vitro, respectively. Mitogen-activated protein kinase (MAPK) and autophagy inhibitors were used, to investigate whether the MAPK signaling pathway and autophagy affect the osteogenic differentiation of BMSCs. ISL significantly improved bone formation and reduced bone resorption in mouse femurs without inducing any detectable toxicity in critical organs such as the liver, kidney, brain, heart, and spleen. In vitro experiments showed that ISL enhanced the proliferation and osteogenic differentiation of BMSCs and that its osteogenic effect was attenuated by p38/extracellular regulated protein kinase (ERK) and autophagy inhibitors. Further studies showed that the inhibition of phosphorylated p38/ERK blocked ISL autophagy in BMSCs. ISL promoted the osteogenic differentiation of BMSCs through the p38/ERK-autophagy pathway and was therapeutically effective in treating osteoporosis in ovariectomized mice without any observed toxicity to vital organs. These results strongly suggest the promising potential of ISL as a safe and efficacious candidate drug for the treatment of osteoporosis.

Nano-Photosensitizer Directed Targeted Phototherapy Effective Against Oral Cancer in Animal Model.

Background: Photodynamic therapy (PDT) has emerged as a promising strategy for oral cancer treatment. Verteporfin is a powerful photosensitizer and widely used in the treatment of macular degeneration. However, rare work has reported its potential in the treatment of oral cancer. Methods: In this study, we introduce an innovative approach of nano-photosensitizer based on Verteporfin, which was prepared by utilizing macrophage membrane to coat Verteporfin-loaded zeolitic imidazolate framework 8 (ZIF-8) for effective photodynamic therapy against oral cancer. Nanoparticle characteristics were assessed including size, zeta potential, and PDI. Cellular uptake studies were conducted using CAL-27 cells. Furthermore, inhibitory effects in both in vitro and in vivo settings were observed, ensuring biosafety. Assessment of anticancer efficacy involved tumor volume measurement, histological analyses, and immunohistochemical staining. Results: In vitro experiments indicated that the nano-photosensitizer showed efficient cellular uptake in the oral cancer cells. Upon the laser irradiation, the nano-photosensitizer induced the generation of reactive oxygen species (ROS), leading to cancer cell apoptosis. The in vivo experiments indicated that the coating with cell membranes enhanced the circulation time of nano-photosensitizer. Moreover, the specificity of the nano-photosensitizer to the cancer cells was also improved by the cell membrane-camouflaged structure in the tumor-bearing mouse model, which inhibited the tumor growth significantly by the photodynamic effect in the presence of laser irradiation. Conclusion: Overall, our findings demonstrate the potential of macrophage membrane-coated ZIF-8-based nanoparticles loaded with Verteporfin for effective photodynamic therapy in oral cancer treatment. This nano-system holds promise for synergistic cancer therapy by combining the cytotoxic effects of PDT with the activation of the immune system, providing a novel therapeutic strategy for combating cancer.

Bismuth nanoclusters on nitrogen-doped porous carbon nanoenzyme for cancer therapy.

Among the emerging cancer therapeutic methods, nanocatalytic therapy through the rational design of nanozymes is considered to be a promising strategy. However, high-performance nanozymes with the ability to catalyze the production of toxic substances to efficiently kill cancer cells are still highly desired. Herein, we fabricate bismuth nanoclusters loaded on nitrogen-doped porous carbon (Bi-NC) as a nanozyme for cancer therapy. The Bi-NC nanozyme displays both peroxidase (POD) and glutathione oxidase (GSHOx) biomimetic enzymatic activities, especially in a tumor microenvironment (TME), which catalyzes the production of hydroxyl radicals (·OH) and depletes antioxidant glutathione (GSH), simultaneously. Moreover, Bi-NC exhibits good photothermal conversion performance under near-infrared light irradiation. After surface modification with hyaluronic acid (HA) to improve the dispersity of nanoparticles and their accumulation in tumor tissues, Bi-NC@HA exhibits remarkable antitumor effects through the synergistic effect of catalytic and photothermal therapy. This work provides a new pathway for designing high-performance nanozymes for cancer catalytic therapy.

Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation.

Introduction: Excessive alcohol consumption leads to a myriad of detrimental health effects, including alcohol-associated liver disease (ALD). Unfortunately, no available treatments exist to combat the progression of ALD beyond corticosteroid administration and/or liver transplants. Dihydromyricetin (DHM) is a bioactive polyphenol and flavonoid that has traditionally been used in Chinese herbal medicine for its robust antioxidant and anti-inflammatory properties. It is derived from many plants, including Hovenia dulcis and is found as the active ingredient in a variety of popular hangover remedies. Investigations utilizing DHM have demonstrated its ability to alleviate ethanol-induced disruptions in mitochondrial and lipid metabolism, while demonstrating hepatoprotective activity. Methods: Female c57BL/6J mice (n = 12/group) were treated using the Lieber DeCarli forced-drinking and ethanol (EtOH) containing liquid diet, for 5 weeks. Mice were randomly divided into three groups: (1) No-EtOH, (2) EtOH [5% (v/v)], and (3) EtOH [5% (v/v)] + DHM (6 mg/mL). Mice were exposed to ethanol for 2 weeks to ensure the development of ALD pathology prior to receiving dihydromyricetin supplementation. Statistical analysis included one-way ANOVA along with Bonferroni multiple comparison tests, where p ≤ 0.05 was considered statistically significant. Results: Dihydromyricetin administration significantly improved aminotransferase levels (AST/ALT) and reduced levels of circulating lipids including LDL/VLDL, total cholesterol (free cholesterol), and triglycerides. DHM demonstrated enhanced lipid clearance by way of increased lipophagy activity, shown as the increased interaction and colocalization of p62/SQSTM-1, LC3B, and PLIN-1 proteins. DHM-fed mice had increased hepatocyte-to-hepatocyte lipid droplet (LD) heterogeneity, suggesting increased neutralization and sequestration of free lipids into LDs. DHM administration significantly reduced prominent pro-inflammatory cytokines commonly associated with ALD pathology such as TNF-α, IL-6, and IL-17. Discussion: Dihydromyricetin is commercially available as a dietary supplement. The results of this proof-of-concept study demonstrate its potential utility and functionality as a cost-effective and safe candidate to combat inflammation and the progression of ALD pathology.

[Antiarrhythmic active components in traditional Chinese medicine acting on potassium channels].

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.

Dietary Supplementation of 25-Hydroxyvitamin D3 Improves Growth Performance, Antioxidant Capacity and Immune Function in Weaned Piglets.

This study was conducted to evaluate the effects of 25-hydroxyvitamin D3 (25(OH)VD3) and Vitamin D3 (VD3) supplemented in the diet of weaned piglets on their growth performance, bone quality, intestinal integrity, immune function and antioxidant capacity. A total of 192 weaned piglets were allocated into four groups and they were fed a control diet containing 2000 IU VD3 (negative control, NC), NC + 100 ppm colistin sulfate (positive control, PC), NC + 2000 IU VD3 (VD3) and NC + 2000 IU 25(OH)VD3 (25(OH)VD3). The results showed that 25(OH)VD3 improved the growth performance, bone quality and antioxidase activity of piglets compared with the other groups. Meanwhile, 25(OH)VD3 up-regulated ileal mRNA expressions of tight junction proteins and host defense peptides. The VD3 group had an increased intestinal sIgA content and mRNA expression of pBD-1 compared with the NC group. Both groups of VD3 and 25(OH)VD3 altered the microbial ß-diversity compared with the NC group, and 25(OH)VD3 increased ileal concentrations of acetate and butyrate. In conclusion, our findings indicated that a regular dosage of 2000 IU VD3 in the weaned piglets' diet did not achieve optimal antioxidant capacity and immune function. 25(OH)VD3 had better growth performance than VD3 at the same inclusion level, which is associated with the improved intestinal integrity and antioxidant capacity.

Integrating pharmacological evaluation and computational identification for deciphering the action mechanism of Yunpi-Huoxue-Sanjie formula alleviates diabetic cardiomyopathy.

Background: Yunpi-Huoxue-Sanjie (YP-SJ) formula is a Chinese herbal formula with unique advantages for the treatment of diabetic cardiovascular complications, such as Diabetic cardiomyopathy (DCM). However, potential targets and molecular mechanisms remain unclear. Therefore, our research was designed to evaluate rat myocardial morphology, fat metabolism and oxidative stress to verify myocardial protective effect of YP-SJ formula in vivo. And then to explore and validate its probable mechanism through network pharmacology and experiments in vitro and in vivo. Methods: In this study, DCM rats were randomly divided into five groups: control group, model group, and three YP-SJ formula groups (low-dose, middle-dose, and high-dose groups). Experimental rats were treated with 6 g/kg/d, 12 g/kg/d and 24 g/kg/d YP-SJ formula by gavage for 10 weeks, respectively. Cardiac function of rats was measured by high-resolution small-animal imaging system. The cells were divided into control group, high glucose group, high glucose + control serum group, high glucose + dosed serum group, high glucose + NC-siRNA group, high glucose + siRNA-FoxO1 group. The extent of autophagy was measured by flow cytometry, immunofluorescence, and western blotting. Results: It was found that YP-SJ formula could effectively improve cardiac systolic function in DCM rats. We identified 46 major candidate YP-SJ formula targets that are closely related to the progression of DCM. Enrichment analysis revealed key targets of YP-SJ formula related to environmental information processing, organic systems, and the metabolic occurrence of reactive oxygen species. Meanwhile, we verified that YP-SJ formula can increase the expression of forkhead box protein O1 (FoxO1), autophagy-related protein 7 (Atg7), Beclin 1, and light chain 3 (LC3), and decrease the expression of phosphorylated FoxO1 in vitro and in vivo. The results showed that YP-SJ formula could activate the FoxO1 signaling pathway associated with DCM rats. Further experiments showed that YP-SJ formula could improve cardiac function by regulating autophagy. Conclusion: YP-SJ formula treats DCM by modulating targets that play a key role in autophagy, improving myocardial function through a multi-component, multi-level, multi-target, multi-pathway, and multi-mechanism approach.

Drosophila melanogaster diabetes models and its usage in the research of anti-diabetes management with traditional Chinese medicines.

The prevalence of diabetes mellitus (DM) is increasing rapidly worldwide, but the underlying molecular mechanisms of disease development have not been elucidated, and the current popular anti-diabetic approaches still have non-negligible limitations. In the last decades, several different DM models were established on the classic model animal, the fruit fly (Drosophila melanogaster), which provided a convenient way to study the mechanisms underlying diabetes and to discover and evaluate new anti-diabetic compounds. In this article, we introduce the Drosophila Diabetes model from three aspects, including signal pathways, established methods, and pharmacodynamic evaluations. As a highlight, the progress in the treatments and experimental studies of diabetes with Traditional Chinese Medicine (TCM) based on the Drosophila Diabetes model is reviewed. We believe that the values of TCMs are underrated in DM management, and the Drosophila Diabetes models can provide a much more efficient tool to explore its values of it.

Comparing Deep Learning Approaches for Understanding Genotype × Phenotype Interactions in Biomass Sorghum.

We explore the use of deep convolutional neural networks (CNNs) trained on overhead imagery of biomass sorghum to ascertain the relationship between single nucleotide polymorphisms (SNPs), or groups of related SNPs, and the phenotypes they control. We consider both CNNs trained explicitly on the classification task of predicting whether an image shows a plant with a reference or alternate version of various SNPs as well as CNNs trained to create data-driven features based on learning features so that images from the same plot are more similar than images from different plots, and then using the features this network learns for genetic marker classification. We characterize how efficient both approaches are at predicting the presence or absence of a genetic markers, and visualize what parts of the images are most important for those predictions. We find that the data-driven approaches give somewhat higher prediction performance, but have visualizations that are harder to interpret; and we give suggestions of potential future machine learning research and discuss the possibilities of using this approach to uncover unknown genotype × phenotype relationships.

Mechanisms Underlying Soybean Response to Phosphorus Deficiency through Integration of Omics Analysis.

Low phosphorus (P) availability limits soybean growth and yield. A set of potential strategies for plant responses to P deficiency have been elucidated in the past decades, especially in model plants such as Arabidopsis thaliana and rice (Oryza sativa). Recently, substantial efforts focus on the mechanisms underlying P deficiency improvement in legume crops, especially in soybeans (Glycine max). This review summarizes recent advances in the morphological, metabolic, and molecular responses of soybean to phosphate (Pi) starvation through the combined analysis of transcriptomics, proteomics, and metabolomics. Furthermore, we highlight the functions of the key factors controlling root growth and P homeostasis, base on which, a P signaling network in soybean was subsequently presumed. This review also discusses current barriers and depicts perspectives in engineering soybean cultivars with high P efficiency.

Computational identification of Shenshao Ningxin Yin as an effective treatment for novel coronavirus infection (COVID-19) with myocarditis.

BACKGROUND: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the 2019 coronavirus disease (COVID-19), which has killed more than 4.5 million people. SARS-CoV-2 causes severe respiratory distress syndrome by targeting the lungs and also induces myocardial damage. Shenshao Ningxin Yin (SNY) has been used for more than 700 years to treat influenza. Previous randomized controlled trials (RCTs) have demonstrated that SNY can improve the clinical symptoms of viral myocarditis, reverse arrhythmia, and reduce the level of myocardial damage markers. METHODS: This work uses a rational computational strategy to identify existing drug molecules that target host pathways for the treatment of COVID-19 with myocarditis. Disease and drug targets were input into the STRING database to construct proteinɃprotein interaction networks. The Metascape database was used for GO and KEGG enrichment analysis. RESULTS: SNY signaling modulated the pathways of coronavirus disease, including COVID-19, Ras signaling, viral myocarditis, and TNF signaling pathways. Tumor necrosis factor (TNF), cellular tumor antigen p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), and the signal transducer and activator of transcription 3 (STAT3) were the pivotal targets of SNY. The components of SNY bound well with the pivotal targets, indicating there were potential biological activities. CONCLUSION: Our findings reveal the pharmacological role and molecular mechanism of SNY for the treatment of COVID-19 with myocarditis. We also, for the first time, demonstrate that SNY displays multi-component, multi-target, and multi-pathway characteristics with a complex mechanism of action.

Novel multifunctional NIR-II aggregation-induced emission nanoparticles-assisted intraoperative identification and elimination of residual tumor.

Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1-π-A-D2-R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes.

Release and transformation of phosphorus in sediment following seasonal freezing-thawing cycles.

River ice in the upper Yarlung Zangbo River is characterized by seasonal freezing-thawing cycles (SFTC). It is important to explore the effects of SFTC on phosphorus release and transformation from upstream surface sediments to protect the ecosystem of the Yarlung Zangbo River. The process and mechanism of phosphorus release and transformation in sediments following SFTC were investigated in a laboratory simulation experiment. The results showed that after freezing, sediment particles were broken, the specific surface area was increased by 14%, and the particle size was decreased by 43%, which resulted in weakened adsorption of phosphorus by sediments. Moreover, the destruction of organic matter (OM) on the sediment surface will release more ion adsorption sites and promote the release of phosphorus. The bioavailabilities of exchangeable phosphorus (Ex-P), aluminum phosphorus (Al-P) and iron phosphorus (Fe-P) increased by 60.09%, 86.86% and 31.86%, respectively, after freezing. Organic phosphorus (O-P) is used indirectly by organisms, and O-P content showed a significant correlation with OM content. Water affected the oxygen content in sediments during the freezing period, and continuous hypoxia promoted the release and transformation of Fe-P and Al-P.

Shufeiya Recipe Improves Monocrotaline-Induced Pulmonary Hypertension in Rats by Regulating SIRT3/FOXO3a and Its Downstream Signaling Pathways.

Pulmonary hypertension (PH) is a chronic and progressive disease caused by obstructions and functional changes of small pulmonary arteries. Current treatment options of PH are costly with patients needing long-term taking medicine. The traditional Chinese medicine (TCM) compound "Shufeiya Recipe" was used to intervene in monocrotaline- (MCT-) induced pulmonary hypertension in rats. The rats were randomly divided into the control group, model group, positive drug (Sildenafil) group, and Shufeiya Recipe low-, moderate-, and high-dose groups. The improvement effect of the Shufeiya Recipe on the mean pulmonary artery pressure (mPAP) was assessed in PH rats, and pathological staining was used to observe the pathological changes of lung tissue. The impact of the Shufeiya Recipe on oxidative stress damage in rats with pulmonary hypertension and the regulation of SIRT3/FOXO3a and its downstream signaling pathways were determined. The results showed that Shufeiya Recipe could significantly downregulate mPAP and improve lung histopathological changes; downregulate serum levels of reactive oxygen species (ROS); upregulate the concentrations of COX-1 and COX-2 and the activity of Mn-SOD; inhibit oxidative response damage; promote the protein expression of SIRT3, FOXO3a, p-PI3K, p-AKT, and p-eNOS; increase the level of expression of NO, sGC, cGMP, and PKG; and downregulate the level of protein expression of Ras, p-MEK1/2, p-ERK1/2 and c-fos. These results indicate that Shufeiya Recipe can improve MCT-induced pulmonary hypertension in rats by regulating SIRT3/FOXO3a and its downstream PI3K/AKT/eNOS and Ras/ERK signaling pathways.

Network Pharmacology and Molecular Docking Analysis of Shufeiya Recipe in the Treatment of Pulmonary Hypertension.

Objective: This study is aimed at exploring the molecular mechanism of Shufeiya recipe in the treatment of pulmonary hypertension (PH) using network pharmacology and molecular docking analysis. Methods: Active components and their target proteins in the recipe were screened using the TCMSP database. PH-related core proteins were screened using GeneCards, STRING database, and Cytoscape-v3.8.2. Common proteins were obtained by intersection of the target proteins of these recipe active components and pH-related core proteins. Rx64 4.0.2 software was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the common proteins to obtain pathway-enriched proteins, and then core enriched proteins were further screened. We analyzed the relationship between the active components and pathway-enriched proteins using Cytoscape-v3.8.2. AutoDock Vina was used to dock their core proteins into the components. Results: Shufeiya recipe contained 67 active components. 61 common proteins of the target proteins of the active components and PH-related core proteins were obtained. The treatment involved both functional and pathway regulations. The core pathway-enriched proteins were prostaglandin G/H synthase 2 (PTGS2), epidermal growth factor receptor (EGFR), and RAC-alpha serine/threonine-protein kinase (AKT1), and their binding energies to the corresponding components were all less than -5 kJ•mol-1. Conclusion: It was found that the main mechanism might be the active components acting on the core pathway-enriched proteins to regulate related signaling pathways, thereby playing roles in anticoagulation, vasodilation, anti-PASMC proliferation, promotion of PAECs apoptosis, inhibition of oxidative stress, and anti-inflammatory effects.

Effects of 25(OH)VD3 on Growth Performance, Pork Quality and Calcium Deposit in Growing-Finishing Pigs.

The study was conducted to evaluate the effects of 25(OH)VD3 with different inclusion levels of 0, 25, 50 and 75 µg/kg in the diet on growth performance, nutrient digestibility, bone properties and pork quality in growing-finishing pigs. The results showed that the average daily gain (p < 0.05) and body weight (p < 0.10) of pigs showed a trend of increasing quadratically as inclusion levels of 25(OH)VD3 increased. Dietary supplementation of 50 µg/kg 25(OH)VD3 increased calcium digestibility compared with the 0 µg/kg group (p < 0.05), and calcium and phosphorus digestibility increased quadratically as inclusion levels of 25(OH)VD3 increased (p < 0.05). Dietary supplementation of 50 µg/kg 25(OH)VD3 increased concentrations of polyunsaturated fatty acids, and decreased contents of saturated and monounsaturated fatty acids in the longissimus dorsi of pigs (p < 0.05). The addition of 25, 50 and 75 µg/kg 25(OH)VD3 to the diet increased breaking strength and bone stiffness in the tibia compared with the 0 µg/kg group (p < 0.05). Dietary supplementation of 50 µg/kg 25(OH)VD3 improved the activities of superoxide dismutase (SOD) and catalase (CAT), and increased the messenger RNA (mRNA) expression of Cu/Zn SOD in the longissimus dorsi compared with the 0 µg/kg group (p < 0.05). Supplementing 50 µg/kg 25(OH)VD3 improved the mRNA expression of calcium-binding protein D9k (CaBP-D9k) and D28k (CaBP-D28K) in the liver compared with the 0 µg/kg 25(OH)D3 group (p < 0.05). In conclusion, a diet with an added dose of 50 µg/kg 25(OH)VD3 showed a greatest growth performance of growing-finishing pigs, and 25(OH)VD3 enhanced calcium deposition and antioxidant capacity in the longissimus dorsi, which may be associated with improved expression of calcium ion channel proteins.

Phosphate (Pi) Starvation Up-Regulated GmCSN5A/B Participates in Anthocyanin Synthesis in Soybean (Glycine max) Dependent on Pi Availability.

Phosphorus (P) is an essential macronutrient for plant growth and development. Among adaptive strategies of plants to P deficiency, increased anthocyanin accumulation is widely observed in plants, which is tightly regulated by a set of genes at transcription levels. However, it remains unclear whether other key regulators might control anthocyanin synthesis through protein modification under P-deficient conditions. In the study, phosphate (Pi) starvation led to anthocyanin accumulations in soybean (Glycine max) leaves, accompanied with increased transcripts of a group of genes involved in anthocyanin synthesis. Meanwhile, transcripts of GmCSN5A/B, two members of the COP9 signalosome subunit 5 (CSN5) family, were up-regulated in both young and old soybean leaves by Pi starvation. Furthermore, overexpressing GmCSN5A and GmCSN5B in Arabidopsis thaliana significantly resulted in anthocyanin accumulations in shoots, accompanied with increased transcripts of gene functions in anthocyanin synthesis including AtPAL, AtCHS, AtF3H, AtF3'H, AtDFR, AtANS, and AtUF3GT only under P-deficient conditions. Taken together, these results strongly suggest that P deficiency leads to increased anthocyanin synthesis through enhancing expression levels of genes involved in anthocyanin synthesis, which could be regulated by GmCSN5A and GmCSN5B.