Integrated metabolome and transcriptome analyses reveal the molecular mechanism underlying dynamic metabolic processes during taproot development of Panax notoginseng.

BACKGROUND: Panax notoginseng (Burk) F. H. Chen is one of the most famous Chinese traditional medicinal plants. The taproot is the main organ producing triterpenoid saponins, and its development is directly linked to the quality and yield of the harvested P. notoginseng. However, the mechanisms underlying the dynamic metabolic changes occurring during taproot development of P. notoginseng are unknown. RESULTS: We carried out metabolomic and transcriptomic analyses to investigate metabolites and gene expression during the development of P. notoginseng taproots. The differentially accumulated metabolites included amino acids and derivatives, nucleotides and derivatives, and lipids in 1-year-old taproots, flavonoids and terpenoids in 2- and 3-year-old taproots, and phenolic acids in 3-year-old taproots. The differentially expressed genes (DEGs) are related to phenylpropanoid biosynthesis, metabolic pathway and biosynthesis of secondary metabolites at all three developmental stages. Integrative analysis revealed that the phenylpropanoid biosynthesis pathway was involved in not only the development of but also metabolic changes in P. notoginseng taproots. Moreover, significant accumulation of triterpenoid saponins in 2- and 3-year-old taproots was highly correlated with the up-regulated expression of cytochrome P450s and uridine diphosphate-dependent glycosyltransferases genes. Additionally, a gene encoding RNase-like major storage protein was identified to play a dual role in the development of P. notoginseng taproots and their triterpenoid saponins synthesis. CONCLUSIONS: These results elucidate the molecular mechanism underlying the accumulation of and change relationship between primary and secondary metabolites in P. notoginseng taproots, and provide a basis for the quality control and genetic improvement of P. notoginseng.

YY1 Lactylation Aggravates Autoimmune Uveitis by Enhancing Microglial Functions via Inflammatory Genes.

Activated microglia in the retina are essential for the development of autoimmune uveitis. Yin-Yang 1 (YY1) is an important transcription factor that participates in multiple inflammatory and immune-mediated diseases. Here, an increased YY1 lactylation in retinal microglia within in the experimental autoimmune uveitis (EAU) group is observed. YY1 lactylation contributed to boosting microglial activation and promoting their proliferation and migration abilities. Inhibition of lactylation suppressed microglial activation and attenuated inflammation in EAU. Mechanistically, cleavage under targets & tagmentation ï¼ˆCUT&Tag） analysis revealed that YY1 lactylation promoted microglial activation by regulating the transcription of a set of inflammatory genes, including STAT3, CCL5, IRF1, IDO1, and SEMA4D. In addition, p300 is identified as the writer of YY1 lactylation. Inhibition of p300 decreased YY1 lactylation and suppressed microglial inflammation in vivo and in vitro. Collectively, the results showed that YY1 lactylation promoted microglial dysfunction in autoimmune uveitis by upregulating inflammatory cytokine secretion and boosting cell migration and proliferation. Therapeutic effects can be achieved by targeting the lactate/p300/YY1 lactylation/inflammatory genes axis.

Exploring the potential mechanism and molecular targets of Taohong Siwu Decoction against deep vein thrombosis based on network pharmacology and analysis docking.

This study aims to investigate the mechanism of Taohong Siwu Decoction (THSWD) against deep vein thrombosis (DVT) using network pharmacology and molecular docking technology. We used the Traditional Chinese Medicine Systems Pharmacology database and reviewed literature to identify the main chemical components of THSWD. To find targets for DVT, we consulted GeneCards, Therapeutic Target Database, and PharmGKB databases. We used Cytoscape 3.8.2 software to construct herb-disease-gene-target networks. Additionally, we integrated drug targets and disease targets on the STRING platform to create a protein-protein interaction network. Then, we conducted Kyoto Encyclopedia of Genes and Genomes and gene ontology analysis. Finally, We employed the molecular docking method to validate our findings. We identified 56 potential targets associated with DVT and found 61 effective components. beta-sitosterol, quercetin, and kaempferol were the most prominent among these components. Our analysis of the protein-protein interaction network revealed that IL6, L1B, and AKT1 had the highest degree of association. Gene ontology analysis showed that THSWD treatment for DVT may involve response to inorganic substances, negative regulation of cell differentiation, plasma membrane protein complex, positive regulation of phosphorylation, and signaling receptor regulator activity. Kyoto Encyclopedia of Genes and Genomes analysis indicated that lipid and atherosclerosis, pathways in cancer, as well as the PI3K-Akt pathway are the main signal pathways involved. Molecular docking results demonstrated strong binding affinity between beta-sitosterol, quercetin, kaempferol, and AKT1 proteins as well as IL1B and IL6 proteins. The main targets for THSWD treatment of DVT may include AKT1, IL1B, and IL6. Beta-sitosterol, quercetin, and kaempferol may be the active ingredients responsible for producing this effect. These compounds may slow down the progression of DVT by regulating the inflammatory response through the PI3K/Akt pathway.

Ginsenosides and Tumors: A Comprehensive and Visualized Analysis of Research Hotspots and Antitumor Mechanisms.

Background: Ginsenoside, the main active constituent of traditional Chinese medicine Ginseng, has been shown to play an important role in the prevention and treatment of cancer. However, the literature as well as the antitumor mechanisms of ginsenosides has not yet been systematically studied. Methods: We screened all relevant literature on ginsenosides and tumors from Web of Science during 2001-2021 and analyzed the extracted terms of these publications by VOSviewer and CiteSpace. DAVID online tool was used to perform Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathways analysis of ginsenoside-related genes. Cytoscape and String software were used to construct the interaction networks of ginsenoside-related genes and corresponding proteins. Results: A total of 919 publications were included in the study. A total of 122 identified keywords were mainly divided into 3 clusters: "pharmacological function research", "functional validation in animal models" and "anti-tumor efficacy and mechanism". The keywords of "oxidative stress" had the strongest citation burst in the past 5 years. A total of 50 genes were identified as ginsenoside-related genes in tumors. They have the function of regulating gene expression and apoptosis, and they are closely related to signaling pathways in cancers. Ginsenoside-related genes form a complex interactional network, in which TP53 and IL-6 are centrally located. Conclusions: We explored and revealed research hotspots related to the ginsenosides and tumors. More precise anti-tumor mechanism research will be promising in the future. TP53 and IL-6 may be the key points to comprehending the anti-tumor mechanism of ginsenosides.

Assessment of water enema PET/CT: an effective imaging technique for the diagnosis of incidental colorectal 18F-FDG uptake.

BACKGROUND: To validate the feasibility of water enema PET/CT (WE-PET/CT) in incidental colorectal 18F-FDG uptake and improve the accuracy of diagnosing colorectal neoplastic lesions. METHODS: We retrospectively analysed the electronic records of 338 patients undergoing common PET/CT and WE-PET/CT at our hospital. PET/CT results were correlated with colonoscopy pathology and follow-up results. The ROC contrast curve was plotted to evaluate the accuracy of SUVmax on common PET/CT and WE-PET/CT for detecting neoplastic lesions. SUVmax and the median retention indexes (RIs) of cancerous, precancerous, and benign lesions and physiologic uptake were compared. RESULTS: The sensitivity, specificity and accuracy of diagnosing neoplastic lesions with common PET/CT were 84.0%, 78.3% and 80.2%, respectively. The corresponding results with WE-PET/CT were 95.8%, 96.5% and 96.2%. The AUC of SUVmax on WE-PET/CT was significantly higher than that on common PET/CT (0.935 vs. 0.524, p < 0.001). The median SUVmax on WE-PET/CT was significantly higher than that on common PET/CT in cancerous and precancerous lesions, and significantly decreased in benign lesions and physiologic uptake (p < 0.001). The RI was significantly different between cancerous lesions and physiologic uptake, between precancerous lesions and physiologic uptake, between benign lesions and physiologic uptake, and between cancerous and benign lesions (p < 0.05). CONCLUSIONS: WE-PET/CT is a noninvasive, well-tolerated and effective technique for diagnosing incidental colorectal 18F-FDG uptake. It is helpful for a timely colonoscopy and can effectively avoid an unnecessary colonoscopy for incidental colorectal 18F-FDG uptake.

Based on network pharmacology and molecular docking to explore the molecular mechanism of Ginseng and Astragalus decoction against postmenopausal osteoporosis.

Traditional Chinese medicine suggests that Ginseng and Astragalus Decoction (GAD) may effectively treat postmenopausal osteoporosis (PMO). However, the exact mechanism of action for GAD remains unclear. This study aims to utilize network pharmacology and molecular docking technology to explore the potential mechanism of GAD in treating PMO. The main chemical components of GAD were identified by consulting literature and traditional Chinese medicine systems pharmacology database. GeneCards and online mendelian inheritance in man were used to identify PMO disease targets, and Cytoscape 3.8.2 software was used to construct a herb-disease-gene-target network. The intersection of drug targets and disease targets was introduced into the search tool for the retrieval of interacting genes platform to construct a protein-protein interaction network. Additionally, we further conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, followed by molecular docking between active ingredients and core protein targets. We have identified 59 potential targets related to the treatment of PMO by GAD, along with 33 effective components. Quercetin and kaempferol are the compounds with higher degree. In the protein-protein interaction network, IL6, AKT1, and IL1B are proteins with high degree. The enrichment analysis of gene ontology and KEEG revealed that biological processes involved in treating PMO with GAD mainly include response to hormones, positive regulation of phosphorylation, and regulation of protein homodimerization activity. The signal pathways primarily include Pathways in cancer, PI3K-Akt signaling pathway, and AGE-RAGE signaling pathway. Molecular docking results indicate that kaempferol and quercetin have a high affinity for IL6, AKT1, and IL1B. Our research predicts that IL6, AKT1, and IL1B are highly likely to be potential targets for treating PMO with GAD. PI3K/AKT pathway and AGE-ARGE pathway may play an important role in PMO.

Pharmacological and Pathological Effects of Mulberry Leaf Extract on the Treatment of Type 1 Diabetes Mellitus Mice.

This study investigated the pharmacological and pathological effects of aqueous mulberry leaf extract on type 1 diabetes mellitus mice induced with an intraperitoneal injection of streptozotocin (STZ). Diabetic mice were randomized into six groups: control (normal group), model, metformin-treated mice, and high-dose, medium-dose, and low-dose mulberry. The mulberry-treated mice were divided into high-, medium-, and low-dose groups based on the various doses of aqueous mulberry leaf extract during gavage. The efficacy of the six-week intervention was evaluated by measuring levels of fasting plasma glucose, alkaline phosphatase, alanine aminotransferase, aspartate transaminase, blood urea nitrogen, gamma-glutamyl transferase, glucose, high-density lipoprotein cholesterol, lactate dehydrogenase, and low-density lipoprotein cholesterol and recording body weight. Results revealed that mulberry leaf extract exhibited an ideal hypoglycemic effect, and the high-dose group was the most affected. Histology analysis, glycogen staining and apoptosis detection were used to study the extract's effects on the liver, kidney, and pancreatic cells of diabetic mice, enabling the assessment of its effectiveness and complications on a clinical and theoretical basis. It was shown that a certain concentration of aqueous mulberry leaf extract repaired the islet cells of type 1 diabetes mellitus mice, promoting normal insulin secretion. Herein, it was confirmed that mulberry leaf could be used to develop new hypoglycemic drugs or functional health food with broad applicability.

Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of Huang-Qi-Gui-Zhi-Wu-Wu decoction against deep vein thrombosis.

BACKGROUND: Huangqi Guizhi Wuwu decoction (HQGZWWD) has been used to treat and prevent deep vein thrombosis (DVT) in China. However, its potential mechanisms of action remain unclear. This study aimed to utilize network pharmacology and molecular docking technology to elucidate the molecular mechanisms of action of HQGZWWD in DVT. METHODS: We identified the main chemical components of HQGZWWD by reviewing the literature and using a Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. We used GeneCards and Online Mendelian Inheritance in Man databases to identify the targets of DVT. Herb-disease-gene-target networks using Cytascape 3.8.2 software; a protein-protein interaction (PPI) network was constructed by combining drug and disease targets on the STRING platform. Additionally, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking verification of active components and core protein targets was conducted. RESULTS: A total of 64 potential targets related to DVT were identified in HQGZWWD, with 41 active components; quercetin, kaempferol, and beta-sitosterol were the most effective compounds. The PPI network analysis revealed that AKT1, IL1B, and IL6 were the most abundant proteins with the highest degree. GO analysis indicated that DVT treatment with HQGZWWD could involve the response to inorganic substances, positive regulation of phosphorylation, plasma membrane protein complexes, and signaling receptor regulator activity. KEGG analysis revealed that the signaling pathways included pathways in cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. The molecular docking results indicated that quercetin, kaempferol, and beta-sitosterol exhibited strong binding affinities for AKT1, IL1B, and IL6. CONCLUSION: Our study suggests that AKT1, IL1B, and IL6 are promising targets for treating DVT with HQGZWWD. The active components of HQGZWWD likely responsible for its effectiveness against DVT are quercetin, kaempferol, and beta-sitosterol, they may inhibit platelet activation and endothelial cell apoptosis by regulating the PI3K/Akt and MAPK signaling pathways, slowing the progression of DVT.

YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2.

BACKGROUND: Ocular neovascularization is a leading cause of blindness. Retinal microglia have been implicated in hypoxia-induced angiogenesis and vasculopathy, but the underlying mechanisms are not entirely clear. Lactylation is a novel lactate-derived posttranslational modification that plays key roles in multiple cellular processes. Since hypoxia in ischemic retinopathy is a precipitating factor for retinal neovascularization, lactylation is very likely to be involved in this process. The present study aimed to explore the role of lactylation in retinal neovascularization and identify new therapeutic targets for retinal neovascular diseases. RESULTS: Microglial depletion by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 suppresses retinal neovascularization in oxygen-induced retinopathy. Hypoxia increased lactylation in microglia and accelerates FGF2 expression, promoting retinal neovascularization. We identify 77 sites of 67 proteins with increased lactylation in the context of increased lactate under hypoxia. Our results show that the nonhistone protein Yin Yang-1 (YY1), a transcription factor, is lactylated at lysine 183 (K183), which is regulated by p300. Hyperlactylated YY1 directly enhances FGF2 transcription and promotes angiogenesis. YY1 mutation at K183 eliminates these effects. Overexpression of p300 increases YY1 lactylation and enhances angiogenesis in vitro and administration of the p300 inhibitor A485 greatly suppresses vascularization in vivo and in vitro. CONCLUSIONS: Our results suggest that YY1 lactylation in microglia plays an important role in retinal neovascularization by upregulating FGF2 expression. Targeting the lactate/p300/YY1 lactylation/FGF2 axis may provide new therapeutic targets for proliferative retinopathies.

Qilong capsule alleviates ponatinib-induced ischemic stroke in a zebrafish model by regulating coagulation, inflammation and apoptosis.

ETHOPHARMACOLOGICAL RELEVANCE: Qilong capsule (QLC) is a compound traditional Chinese medicine commonly used to treat ischemic stroke (IS). QLC is made of eight kinds of medicinal materials. It has two kinds of monarch medicine and six kinds of minister medicine. However, the pharmacodynamic mechanism of QLC is still unknown. AIM OF THE STUDY: The aim of this paper was to evaluate the pharmacology mechanism of QLC against ischemic stroke through coagulation, inflammation and apoptosis. MATERIALS AND METHODS: We used an existing zebrafish model to explore the protective mechanism of QLC on IS. We treated normally-developing zebrafish larvae with QLC and ponatinib 2 days post fertilization (dpf), and used the area of cerebral vascular thrombosis, red blood cell staining intensity, and brain cell apoptosis to quantitate QLC efficacy against IS. Evaluation of brain inflammation in zebrafish by observing macrophage aggregation and migration. In addition, we also explored the effect of QLC on zebrafish angiogenesis. Quantitative polymerase chain reaction (qPCR) was used to detect changes in the expression of genes involved in coagulation, inflammation, vascular endothelium, and apoptosis. RESULTS: We found that QLC reduced the area affected by ponatinib-induced cerebral vascular embolism, erythrocyte staining intensity, and the number of apoptotic brain cells. For inflammation, QLC can improve the aggregation and migration of macrophages. QLC can significantly promote the formation of blood vessels in zebrafish. qPCR showed that QLC inhibited the expression of genes related to coagulation, inflammation, and apoptosis. CONCLUSION: Qilong capsule had a significant protective efficacy in ponatinib-induced IS.

HS-SPME coupled with GC-MS for elucidating differences between the volatile components in wild and cultivated Atractylodes chinensis.

INTRODUCTION: Atractylodes chinensis is a Chinese herb that is used in traditional medicine; it contains volatile components that have enormous potential for pharmaceutical, food, and cosmetic applications. The destruction of wild resources demands significant improvement in the quality of artificial cultivation of Atractylodes chinensis. However, little is known about the compositional differences in the volatile substances derived from the wild and cultivated varieties of Atractylodes chinensis. OBJECTIVES: We aimed to evaluate the specific components of Atractylodes chinensis and analyse the similarities and differences between the volatile components and metabolic pathways in the wild and cultivated varieties. MATERIAL AND METHODS: Metabolomic analysis using gas chromatography-mass spectrometry (GC-MS) was employed following the extraction of volatile components from Atractylodes chinensis using headspace solid-phase microextraction (HS-SPME). RESULTS: A total of 167 volatile metabolites were extracted, and 137 substances were matched with NIST and Wiley databases. Among them, 76 compounds exhibited significant differences between the two sources; these mainly included terpenes, aromatics, and esters. KEGG enrichment analysis indicated that the differential metabolites were primarily involved in the biosynthesis of secondary metabolites, terpene biosynthesis, and limonene and pinene degradation; all these pathways have geranyl diphosphate (GDP) as the common link. CONCLUSION: The total content of volatile substances extracted from wild Atractylodes chinensis was 2.5 times higher than that from the cultured variety; however, each source had different dominant metabolites. This study underscores the necessity for protecting wild Atractylodes chinensis resources, while enhancing the quality of cultivated Atractylodes chinensis.

Qilong Capsule Alleviated MPTP-Induced Neuronal Defects by Inhibiting Apoptosis, Regulating Autophagy in Zebrafish Embryo Model.

Qilong capsule (QLC) originates from the famous "Buyang Huanwu decoction" prescription. It is representative of drugs used in China during recovery from stroke, but its neuroprotective mechanism of action remains obscure. HPLC was used to evaluate the similarity of 10 batches of QLC samples. Then we used a zebrafish model to study the neuroprotective effect of QLC. At 24 hpf, embryos were treated with QLC and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and zebrafish were observed the neuronal length and the number of apoptotic cells in the brain at 72 hpf. At 120 hpf, we conduct zebrafish behavioural tests. We then also used qPCR to detect the expression of genes related to autophagy and apoptosis. The results showed that QLC significantly reduced the damage of dopaminergic neurons, the number of apoptotic cells in the brain, and alleviated motor disturbances induced by MPTP. We found that the mechanism of QLC activity involved decreased neuron cell death by inhibiting mitochondrial apoptosis and autophagy, promoting autophagy, degradation of alpha-synuclein, and neuron cell growth, and rescuing the function of neurons damaged by MPTP. The results indicated that QLC protected against MPTP-induced neuron injury and provided pharmacological evidence for clinical use of QLC.

Highly Stretchable, Swelling-Resistant, Self-Healed, and Biocompatible Dual-Reinforced Double Polymer Network Hydrogels.

Superior flexibility and toughness can be achieved in bioactive hydrogels by the use of a double polymer network with complementary properties. Inspired by this design principle, we here combine polyacrylic acid (PAA) and sodium alginate (SA) to obtain a dual-reinforced double interpenetrating network (d-DIPN) hydrogel. The dual reinforcement involves ionic cross-linking and introduction of SiO2 nanoparticles, which leads to extraordinary improvements in strength and toughness. Compared with the standard PAA hydrogel that offers an elongation of 240% and a breakage stress of 0.03 MPa, the prepared SA(Ca2+)-PAA-SiO2 hydrogel shows an elongation above 1000% and a breakage stress of 1.62 MPa. Moreover, the combination of strong covalent cross-links and weak reversible interactions provides the d-DIPN hydrogel with swelling resistance and self-healing behavior, adhesive abilities, and shape memory performance. Furthermore, we show that the biocompatibility and bone cell proliferation ability of the hydrogels can be improved through a mineralization process despite an observed reduction in breakage strain and stress. Taken as a whole, our work paves the way for the design of strong and tough hydrogels, with potential applications within biomedicine and particularly tissue engineering.

iPSC-based model of Vogt-Koyanagi-Harada disease for phenotype recapitulation and drug screening.

Vogt-Koyanagi-Harada (VKH) disease, a major blinding eye disease, is characterized by an autoimmune response against melanocytes in multiple organs throughout the body. Currently, the aetiology and pathogenesis of VKH disease are unclear, and the treatment strategy needs to be further optimized. The retinal pigment epithelium (RPE), a monolayer of pigmented cells of the fundus, is essential for maintaining normal visual function and is involved in both the acute and chronic stages of VKH disease. Therefore, the functions of the RPE may play a critical role in the aetiology and treatment of VKH disease. Herein, we established a human induced pluripotent stem cell (hiPSC) RPE model of VKH disease by reprogramming peripheral blood mononuclear cells (PBMCs) into iPSCs and then differentiating them into RPE cells. Patient-derived RPE cells exhibited barrier disruption, impaired phagocytosis, and depigmentation compared with those from normal controls, which was consistent with the features of VKH disease. Furthermore, a small molecular compound targeting EGR2 was found to rescue the barrier and phagocytic functions of the hiPSC-RPE cells through high-throughput virtual screening and functional studies, suggesting a promising strategy for the treatment of VKH disease.

Marsdenia tenacissima genome reveals calcium adaptation and tenacissoside biosynthesis.

Marsdenia tenacissima is a medicinal plant widely distributed in the calcium-rich karst regions of southwest China. However, the lack of a reference genome has hampered the implementation of molecular techniques in its breeding, pharmacology and domestication. We generated the chromosome-level genome assembly in Apocynaceae using combined SMRT sequencing and Hi-C. The genome length was 381.76 Mb, with 98.9% of it found on 11 chromosomes. The genome contained 222.63 Mb of repetitive sequences and 21 899 predicted gene models, with a contig N50 of 6.57 Mb. Phylogenetic analysis revealed that M. tenacissima diverged from Calotropis gigantea at least 13.43 million years ago. Comparative genomics showed that M. tenacissima underwent ancient shared whole-genome duplication. This event, together with tandem duplication, contributed to 70.71% of gene-family expansion. Both pseudogene analysis and selective pressure calculations suggested calcium-related adaptive evolution in the M. tenacissima genome. Calcium-induced differentially expressed genes (DEGs) were mainly enriched in cell-wall-related processes. Domains (e.g. Fasciclin and Amb_all) and cis-elements (e.g. MYB and MYC) frequently occurred in the coding and promoter regions of cell-wall DEGs, respectively, and the expression levels of these genes correlated significantly with those of calcium-signal-related transcription factors. Moreover, calcium addition increased tenacissoside I, G and H contents. The availability of this high-quality genome provides valuable genomic information for genetic breeding and molecular design, and lends insights into the calcium adaptation of M. tenacissima in karst areas.

YY1 transcription factor induces proliferation and aerobic glycolysis of neuroblastoma cells via LDHA regulation.

The present study investigated the effect of transcription factor yin yang 1 (YY1) on aerobic glycolysis and cell proliferation in neuroblastoma and its mechanism. Neuroblastoma cell lines were used to investigate the association between YY1 and lactate dehydrogenase A (LDHA) expression. Cell Counting Kit (CCK)-8 and clone formation experiments were used to detect the cell viability. The interaction of YY1 and LDHA was detected using chromatin immunoprecipitation assay. Glucose uptake, intra/extracellular lactate and pyruvate and LDHA expression were evaluated using standard methods. Reverse transcription quantitative PCR, western blotting and gene overexpression or silencing were undertaken to explore the biological effects and underlying mechanisms of transcriptional regulators in NB cells. The results demonstrated that YY1 was significantly upregulated in neuroblastoma cell lines. The results of aerobic glycolysis and CCK-8 indicated that YY1 significantly promoted the proliferation and aerobic glycolysis of neuroblastoma cells. In addition, chromatin immunoprecipitation-PCR results demonstrated that YY1 was directly bound to the promoter LDHA. Overexpression of LDHA could reverse the inhibitory effect of sh-YY1 on aerobic glycolysis and proliferation of neuroblastoma cells. In conclusion, YY1 could induce aerobic glycolysis and proliferation of neuroblastoma cell lines, and may directly mediate the regulation of LDHA. These findings may provide novel insight for the treatment of neuroblastoma.

Characteristics of heavy metal accumulation and risk assessment in understory Panax notoginseng planting system.

Yunnan Province is the main planting area of the precious Chinese herbal medicines (CHM) Panax notoginseng; however, it locates the geological area with high soil heavy metals in China. The frequent land replacement due to continuous cropping obstacles and excessive application of chemicals makes P. notoginseng prone to be contaminated by heavy metals under the farmland P. notoginseng (FPn) planting. To overcome farmland shortage, understory P. notoginseng (UPn) was developed as a new ecological planting model featured by no chemicals input. However, this newly developed planting system requires urgently the soil-plant heavy metal characteristics and risk assessment. This study aimed to evaluate the pollution status of eight heavy metals in the tillage layer (0-20 cm), subsoil layer (20-40 cm) and the plants of UPn in Lancang County, Yunnan Province. Pollution index (Pi) showed that the contamination degree of heavy metals in the tillage layer and subsoil layer was Cd > Pb > Ni > Cu > Zn > Cr > Hg > As and Pb > Cd > Cu > Ni > Cr > Hg > Zn > As, respectively. Potential ecological risk index (PERI) for the tillage layer and subsoil layer was slight and middle, respectively. The exceeding standard rate of Cd, As, Pb, Hg, Cu in the UPn roots was 5.33%, 5.33%, 13.33%, 26.67% and 1.33%, respectively, while only Cd and Hg in the UPn leaves exceeded the standard 10% and 14%, respectively. The enrichment abilities of Cd and Hg in the roots and leaves of UPn were the strongest, while that of Pb was the weakest. The Hazard index (HI) and target hazard quotient (THQ) of eight heavy metals in the roots and leaves of UPn were less than 1.Therefore, our results prove that Upn has no human health risk and provide a scientific basis for the safety evaluation and extension of UPn.

Human growth hormone supplement promotes human lymphohematopoietic cell reconstitution in immunodeficient mice.

Aim: To investigate the potential of human growth hormone (hGH) to improve human hematopoietic reconstitution in humanized mice. Materials & methods: Immunodeficient mice were conditioned by total body irradiation and transplanted with human CD34+ fetal liver cells. Peripheral blood, spleen and bone marrow were harvested, and levels of human lymphohematopoietic cells were determined by flow cytometry. Results: Supplementation with hGH elevated human lymphohematopoietic chimerism by more than twofold. Treatment with hGH resulted in significantly increased reconstitution of human B cells and myeloid cells in lymphoid organs, enhanced human erythropoiesis in the bone morrow, and improved engraftment of human hematopoietic stem cells. Conclusion: hGH supplementation promotes human lymphohematopoietic reconstitution in humanized mice.

Humanized mice generated by human hematopoietic stem cell transplantation play crucial roles in biomedical investigations. One of the factors hindering the efficacy of their construction is the lack of or insufficient interaction of human cells to mouse cytokines and growth hormones (GHs) that are crucial for hematopoiesis and immune cell differentiation. In this study, we show that injection of human GH significantly improved human hematopoietic stem cell engraftment and function, as well as immune cell reconstitution in humanized mice. Our findings indicate that human cells may not efficiently respond to mouse GH, and generation of immunodeficient mice producing human GH may improve the efficacy of humanized mouse construction.

Nanotechnology-Based Drug Delivery System for Anticancer Active Ingredients from Traditional Chinese Medicines: A Review.

The variable dosage forms of most traditional Chinese medicines (TCMs) could be disadvantaged by low selectivity, poor biological distribution, limited bioavailability with low efficacy, and some adverse effects. These issues limit the control of clinical pharmacodynamics of the antitumor active components. With the progress of science and technology, many new polymer materials and new technologies have emerged, such as nanotechnology, cyclodextrin inclusion, solid dispersion, microcapsule and microsphere technologies. These new technologies provide a good basis for exploring novel TCM dosage forms for overcoming the shortcomings. The increased numbers of new technologies have been used to study TCM dosage forms with remarkable achievements. In this review paper, we will provide a systematic overview of the new dosage forms of nano-formulations and co-medications in relation to nano-delivery systems in an attempt to provide useful references for practical application of active antitumor ingredients from the TCMs.

Analysis of the Influence of Midwife Led Antenatal Clinic on the Delivery Outcomes of Primipara under the Evaluation of Medical Data.

Objective: In order to improve the comprehensive effect of primipara delivery outcomes, the midwife led prenatal clinic of data mining is analyzed to alleviate the negative emotions of patients and improve the delivery results of patients. Methods: A total of 86 patients who were filed in the obstetrics department of our hospital from October 2021 to May 2022 and planned to deliver in our hospital were selected as the research objects. They were divided into the reference group (n = 43) and the observation group (n = 43) according to the random number table method. Among them, the reference group received routine antenatal clinics, and the observation group received midwives' participation in antenatal clinics for intervention. The total duration of labor, the scores of various psychological states including antenatal anxiety (SAS) and antenatal depression (SDS), as well as the pregnancy outcome and delivery compliance rate of the two groups were compared. Results: The psychological state evaluation of delivery in the observation group, whether SAS score or SDS score, was significantly lower than that in the reference group, and the difference was statistically significant. The whole labor process time of patients in the observation group was significantly shorter than that in the reference group, and the difference was statistically significant. The delivery compliance of patients in the observation group during the whole perinatal period was also higher than that of the reference group, and the difference was statistically significant. All P values were<0.05. Conclusion: The antenatal clinic led by midwives can promote primiparas to increase the success rate of natural delivery, improve the treatment compliance of the whole perinatal period, reduce the psychological pressure of primiparas, effectively shorten the total time of production, and have a significant impact on the outcome of delivery. It should be widely used.