Folic acid supplementation prevents high body fat-induced bone loss through TGR5 signaling pathways.

Osteoporosis caused by bone loss is one of the serious global public health problems. Folic acid is a B vitamin with multiple physiological functions such as lipid regulation and antioxidant capacity, and its potential to improve bone loss has attracted our attention. Through NHANES database analysis, we found that folic acid intake was significantly correlated with whole-body bone mineral density (BMD) in people aged 20-60 years, and the association may be mediated by the body fat rate. Male C57Bl/6 mice were fed either a normal diet or a high-fat diet, and folic acid was added to drinking water for supplementation. Our results indicated that mice with high body fat showed bone microstructure damage and bone loss, while folic acid supplementation improved bone quality. At the same time, we found that mice with high body fat exhibited abnormal blood lipids, dysregulation of intestinal flora, and metabolic disorders. Folic acid supplementation improved these phenomena. Through the network analysis of intestinal flora and metabolites, we found that LCA and TGR5 may play important roles. The results showed that folic acid promoted the expression of LCA and TGR5 in mice, increased the phosphorylation of AMPK, and decreased the phosphorylation of NF-κB and ERK, thereby reducing bone loss. In summary, folic acid intake is closely related to BMD, and folic acid supplementation can prevent high body fat-induced bone loss. Our study provides new ideas and an experimental basis for preventing bone loss and osteoporosis.

Integration of network pharmacology and serum medicinal chemistry to investigate the pharmacological mechanisms of QiZhuYangGan Decoction in the treatment of hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Qizhuyanggan Decoction (QZD), a traditional Chinese medicine formula, is frequently utilized in clinical practice for managing hepatic fibrosis. However, the specific target and mechanism of action of QZD for hepatic fibrosis treatment remain unknown. AIM OF THE STUDY: By combining network pharmacology, serum medicinal chemistry, and experimental validation methods, our study aimed to investigate the therapeutic effects of QZD on hepatic fibrosis, the anti-hepatic fibrosis active ingredients, and the possible mechanism of anti-hepatic fibrosis action. MATERIALS AND METHODS: The study aimed to investigate the therapeutic effect of QZD on hepatic fibrosis induced by CCl4 in SD rats, as well as its mechanism of action. The rats were anesthetized intraperitoneally using 3% pentobarbital and were executed after asphyxiation with high concentrations of carbon dioxide. Several techniques were employed to evaluate the efficacy of QZD, including ELISA, Western blot, HYP reagent assay, and various pathological examinations such as HE, Masson, Sirius Red staining, and immunohistochemistry (IHC). Additionally, serum biochemical assays were conducted to assess the effect of QZD on liver injury. Network pharmacology, UPLC, molecular docking, and molecular dynamics simulation were utilized to explore the mechanism of QZD in treating hepatic fibrosis. Finally, experimental validation was performed through ELISA, IHC, RT-qPCR, and Western blot analysis. RESULT: Liver histopathology showed that QZD reduced inflammation and inhibited collagen production, and QZD significantly reduced HA and LN content to treat hepatic fibrosis. Serum biochemical analysis showed that QZD improved liver injury. Network pharmacology combined with UPLC screened six active ingredients and obtained 87 targets for the intersection of active ingredients and diseases. The enrichment analysis results indicated that the PI3K/AKT pathway might be the mechanism of action of QZD in the treatment of hepatic fibrosis, and counteracting the inflammatory response might be one of the pathways of action of QZD. Molecular docking and molecular dynamics simulations showed that the active ingredient had good binding properties with PI3K, AKT, and mTOR proteins. Western blot, ELISA, PCR, and IHC results indicated that QZD may treat hepatic fibrosis by inhibiting the PI3K/AKT/mTOR pathway and suppressing M1 macrophage polarization, while also promoting M2 macrophage polarization. CONCLUSIONS: QZD may be effective in the treatment of hepatic fibrosis by inhibiting the PI3K/AKT/mTOR signaling pathway and M1 macrophage polarization, while promoting M2 macrophage polarization. This provides a strong basis for the clinical application of QZD.

[Textual research on Bungarus Parvus].

Bungarus Parvus, a precious animal Chinese medicinal material used in clinical practice, is believed to be first recorded in Ying Pian Xin Can published in 1936. This study was carried out to analyze the names, geographical distribution, morphological characteristics, ecological habits, poisonousness, and medicinal parts by consulting ancient Chinese medical books and local chronicles, Chinese Pharmacopeia, different processing standards of trditional Chinese medicine(TCM) decoction pieces, and modern literatures. The results showed that the earliest medicinal record of Bungarus Parvus was traced to 1894. In 1930, this medicinal material was used in the formulation of Annao Pills. The original animal, Bungarus multicinctus, was recorded by the name of "Bojijia" in 1521. The morphological characteristics, ecological habits, and poisonousness of the original animal are the same in ancient and modern records. The geographical distribution is similar between the ancient records and modern documents such as China Medicinal Animal Fauna. The dried body of young B. multicinctus is used as Bungarus Parvus, which lack detailed references. As a matter of fact, it is still inconclusive whether there are differences between young snakes and adult snakes in terms of active ingredients, pharmacological effects, and clinical applications. This study clarified the medicinal history and present situation of Bungarus Parvus. On the basis of the results, it is suggested that systematic comparison on young and adult B. multicinctus should be carried out to provide references for revising the medicinal parts of B. multicinctus.

Andrographolide causes p53-independent HCC cell death through p62 accumulation and impaired DNA damage repair.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal cancer characterized by dominant driver mutations, including p53. Consequently, there is an urgent need to search for novel therapeutic agents to treat HCC. Andrographolide (Andro), a clinically available anti-inflammatory phytochemical agent, has shown inhibitory effects against various types of cancer, including HCC. However, the underlying molecular mechanisms of its action remain poorly understood. PURPOSE: This study aims to investigate the molecular mechanisms by which p53 and p62 collectively affect Andro-induced HCC cell death, using both in vitro and in vivo models. METHODS: In vitro cellular experiments were conducted to examine the effects of Andro on cell viability and elucidate its mechanisms of action. In vivo xenograft experiments further validated the anti-cancer effects of Andro. RESULTS: Andro induced dose- and time-dependent HCC cell death while sparing normal HL-7702 hepatocytes. Furthermore, Andro caused DNA damage through the generation of reactive oxygen species (ROS), a critical event leading to cell death. Notably, HCC cells expressing p53 exhibited greater resistance to Andro-induced cell death compared to p53-deficient cells, likely due to the ability of p53 to induce G2/M cell cycle arrest. Additionally, Andro-induced p62 aggregation led to the proteasomal degradation of RAD51 and 53BP1, two key proteins involved in DNA damage repair. Consequently, silencing or knocking out p62 facilitated DNA damage repair and protected HCC cells. Importantly, disruption of either p53 or p62 did not affect the expression of the other protein. These findings were further supported by the observation that xenograft tumors formed by p62-knockout HCC cells displayed increased resistance to Andro treatment. CONCLUSION: This study elucidates the mechanistic basis of Andro-induced HCC cell death. It provides valuable insights for repurposing Andro for the treatment of HCC, regardless of the presence of functional p53.

Melatonin ameliorates sleep-wake disturbances and autism-like behaviors in the Ctnnd2 knock out mouse model of autism spectrum disorders.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical patterns of social interaction and communication, as well as restrictive and repetitive behaviors. In addition, patients with ASD often presents with sleep disturbances. Delta (δ) catenin protein 2 (CTNND2) encodes δ-catenin protein, a neuron-specific catenin implicated in many complex neuropsychiatric diseases. Our previous study demonstrated that the deletion of Ctnnd2 in mice led to autism-like behaviors. However, to our knowledge, no study has investigated the effects of Ctnnd2 deletion on sleep in mice. In this study, we investigated whether the knockout (KO) of exon 2 of the Ctnnd2 gene could induce sleep-wake disorders in mice and identified the effects of oral melatonin (MT) supplementation on Ctnnd2 KO mice. Our results demonstrated that the Ctnnd2 KO mice exhibited ASD-like behaviors and sleep-wake disorders that were partially attenuated by MT supplementation. Overall, our current study is the first to identify that knockdown of Ctnnd2 gene could induce sleep-wake disorders in mice and suggests that treatment of sleep-wake disturbances by MT may benefit to autism-like behaviors causing by Ctnnd2 gene deletion.

Synthetic Antibacterial Quaternary Phosphorus Salts Promote Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing.

Background: Drug-resistant microbes pose a global health concern, requiring the urgent development of effective antibacterial agents and strategies in clinical practice. Therefore, there is an urgent need to explore novel antibacterial materials to effectively eliminate bacteria. The synthesis of quaternary phosphonium salt in haloargentate systems, wherein the phosphorus atom is represented in a cationic form, is a possible strategy for the development of antibacterial materials. Methods: Using (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 4, 6) as a template, we designed three kinds of quaternary phosphorus salts as effective antibacterial agents against drug-resistant bacteria. Results: The synthesized quaternary phosphorus salt of (1,4-DBTPP)Br2 effectively prevented the formation of the bacterial biofilms, and degraded bacterial membranes and cell walls by promoting the production of reactive oxygen species, which exhibited effective therapeutic effects in a rat model of a superficial wound infected with methicillin-resistant Staphylococcus aureus. Conclusion: The quaternary phosphorus salt (1,4-DBTPP)Br2 demonstrated hemocompatibility and low toxicity, revealing its potential in the treatment of clinical infections.

Quantitative and qualitative analysis of Artemisiae Verlotori Folium and Artemisiae Argyi Folium by high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

Artemisiae Argyi Folium (Aiye in Chinese) has been widely used since ancient times. In the Lingnan region (Southern China), the leaf of Artemisia verlotorum Lamotte, which is named Hongjiaoai (HJA) because the roots are red (Hongjiao means red foot in Chinese), has been used as a local substitute for Artemisiae Argyi Folium. The plant has a long medicinal and edible history that can be traced to the Jin Dynasty. However, there is no systematic and reliable method to control the quality of Artemisiae Verlotori Folium. In this study, a comprehensive method involving high-performance liquid chromatography coupled with diode array detection and quadrupole-time-of-flight high-definition mass spectrometry was established to identify and quantify eight constituents (including organic acids and flavonoids) in Artemisiae Verlotori Folium and Artemisiae Argyi Folium as well as high-performance liquid chromatography fingerprints of the two varieties. Moreover, dissimilarities of chemical compositions among the two varieties were further investigated by orthogonal partial least squares discrimination analysis and cluster analysis. This research not only explored the similarities and differences between Artemisiae Verlotori Folium and Artemisiae Argyi Folium in eight components but also provided a qualitative and quantitative analytical method that quickly, accurately, and comprehensively assesses the quality of Artemisiae Verlotori Folium.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

The association of iron status, supplement iron in the first-trimester pregnancy with gestational diabetes mellitus: A nested case-control study.

AIMS: The objective of this study was to examine whether the level of iron and iron supplements in the first-trimester pregnancy is associated with gestational diabetes mellitus (GDM). METHODS: This was a nested case-control study using data from an established cohort in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. Iron status indicators were tested in early pregnancy. Information on iron supplements use was collected by questionnaires. Binary logistic regression was used to obtain odds ratio (OR). The relative excess risk of interaction (RERI) was applied to evaluate the interaction. RESULTS: We observed that pregnant women with normal ferritin levels (≥30 ng/ml) and iron supplements were associated with a 3.701-fold increased risk of GDM (OR: 3.701, 95% CI: 1.689-8.112) compared with the ferritin <30 ng/ml and without iron supplements group. Similarly, pregnant women with normal serum iron (SI) levels (≥9 µmol/L) and iron supplements were associated with a 5.447-fold increased risk of GDM (OR: 5.447, 95% CI: 2.246-13.209) compared with the SI < 9 µmol/L and without iron supplement group. We found an additive interaction between ferritin and iron supplements on the presence of GDM (RERI: 1.164, 95%CI: 0.333-1.994) and SI and iron supplements on the risk of GDM (RERI: 6.375, 95%CI: 4.494-8.256). CONCLUSION: Pregnant women with normal ferritin or SI levels and iron supplements could significantly increase the risks for GDM.

[Comparison on volatile components between Artemisiae Verlotori Folium and Artemisiae Argyi Folium based on GC-MS and chemometrics].

Artemisiae Argyi Folium is commonly used in clinical practice. Artemisiae Verlotori Folium, the dried leaves of Artemisia verlotorum, is often used as a folk substitute for Artemisiae Argyi Folium in Lingnan area. In this study, gas chromatography-triple quadrupole mass spectrometry(GC-MS) was used to detect the volatile oil components of 27 samples of Artemisiae Verlotori Folium and 13 samples of Artemisiae Argyi Folium, and the volatile components were compared between the two species. The internal standard method was combined with multi-reaction monitoring mode(MRM) to determine the content of six major volatile components. Hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were carried out for the content data. The results showed that the Artemisiae Argyi Folium samples had higher content and more abundant volatile oils than the Artemisiae Verlotori Folium samples. Artemisiae Argyi Folium mainly had the components with lower boiling points, while Artemisiae Verlotori Folium mainly had the components with higher boiling points. Terpenoids were the main volatile components in Artemisiae Verlotori Folium(mainly sesquiterpenoids) and Artemisiae Argyi Folium(monoterpenoids). In addition, Artemisiae Argyi Folium had higher content of oxygen-containing derivatives than Artemisiae Verlotori Folium. Furthermore, the stoichiometric analysis showed that the two species could be distinguished by both HCA and OPLS-DA, indicating that the volatile components of the two were significantly different. This study can provide a scientific basis for the quality evaluation and data support for the local rational application of Artemisiae Verlotori Folium in Lingnan.

Polymethoxyflavones from citrus peel: advances in extraction methods, biological properties, and potential applications.

Citrus peel, as an effective component of citrus by-products, contains a large number of natural active components, including pectin, vitamins, dietary fiber, essential oil, phenolic compounds, flavonoids, and so on. With the development of the circular economy, citrus peel has attracted extensive concern in the food industry. The exploitation of citrus peel would assist in excavating potential properties and alleviating the environmental burden. Polymethoxyflavones (PMFs) exist almost in citrus peel, which have remarkable biological activities including antioxidant, anti-inflammatory, anti-cancer, and anti-obesity. Therefore, PMFs from citrus peel have the potential to develop as dietary supplements in the near future. Collectively, it is essential to take action to optimize the extraction conditions of PMFs and make the most of the extracts. This review mainly compiles several extraction methods and bioactivities of PMFs from citrus peel and introduces different applications including food processing, pharmaceutical industry, and plant rhizosphere to develop better utilization of citrus PMFs.

Polymethoxyflavones (PMFs) represent sustainable bioactive compounds that profit for circular economy.Valorization of citrus peel PMFs will bring value-added environmental benefits.Novel techniques improve property and extraction efficiency of PMFs.PMFs obtained from citrus peel could be applied to tea or bakery food processing and pharmaceutical industry.

[A new xanthone from Hypericum lagarocladum].

Repeated silica gel column chromatography, reversed-phase C_(18) column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and semi-preparative medium pressure liquid chromatography were performed to separate and purify the chemical constituents of Hypericum lagarocladum. Spectroscopic methods such as mass spectrometry(MS) and nuclear magnetic resonance(NMR) combined with physicochemical properties were adopted in identifying the structure of the isolated compounds. Ten compounds were isolated from the ethyl acetate fraction of H. lagarocladum and identified as lagarxanthone A(1), 1,7-dihydroxyxanthone(2), 3,4,5-trihydroxyxanthone(3), 2,7-dihydroxy-1-methoxyxanthone(4), 1,3-dihydroxy-7-methoxyxanthone(5), 1,5-dihydroxy-8-methoxyxanthone(6), 3,4-dihydroxy-2-methoxyxanthone(7), 3,4-dihydroxy-5-methoxyxanthone(8), 2,3-dimethoxyxanthone(9), and 2,3,4-trimethoxyxanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from this plant for the first time. These ten compounds were tested for glucose uptake in L6 cells, and the results showed that all the compounds had no significant effect on glucose uptake.

A novel pre-magnetized ZVI/PS pretreatment for improving sludge dewaterability: The role of EPS fractions.

The dewaterability of waste-activated sludge (WAS) has been extensively examined using zero-valent iron (ZVI)-based advanced oxidation processes (AOPs). However, the high dosage and low utilization efficiencies of ZVI cast doubt on the dependability and viability of ZVI-based AOPs. In this study, we successfully demonstrated pre-magnetization as an efficient, chemical-free, and ecological method for improving the efficiency of sludge dewatering by ZVI/persulfate (PS) process, in which the reduction ratios of capillary suction time (CST) and specific resistance to filtration (SRF) increased by 8.67% and 11.06% under optimal conditions, respectively. The highly active Fe2+ released during ZVI corrosion may be more essential than ZVI itself during PS activation, which could be strengthened by pre-magnetization. Both homogeneous and heterogeneous Fe2+ could react with PS to produce aqueous hydroxyl radicals (∙OH) and sulfate radicals (SO4-∙) as well as surface-bound ∙OH and SO4-∙, further decomposing bound-extracellular polymeric substances fractions, broking hydrophilic functional groups and compounds, altering protein secondary structure to expose more hydrophobic sites, and releasing abundant EPS-bound water. Due to the protection of tightly-bound extracellular polymeric substances (TB-EPS) and the competitive oxidation of organics released during the early disintegration stage, radical oxidation primarily occurs at extracellular levels, releasing a bit of intracellular water. Besides, polysaccharides in TB-EPS may function a more significant role in flocculation than proteins, and a porous structure favorable to drainage will be formed after the pre-magnetized ZVI/PS treatment. The cost-benefit analysis further reveals that the Pre-ZVI/PS process presents high reusability and utilization, making it potential for particle application in sludge dewatering.

Guanxin Xiaoban capsules could treat atherosclerosis by affecting the gut microbiome and inhibiting the AGE-RAGE signalling pathway.

Introduction. Atherosclerosis is a chronic disorder in which plaque builds up in the arteries and is associated with several cardiovascular and cerebrovascular diseases such as coronary artery disease, cerebral infarction and cerebral haemorrhage. Therefore, there is an urgent need to discover new medications to treat or prevent atherosclerosis.Hypothesis/Gap Statement. The active components of Guanxin Xiaoban capsules may have an effect on the gut microbiome of patients with atherosclerosis and have a role in their therapeutic targets.Aim. The aim of this study was to identify genes and pathways targeted by active ingredients in Guanxin Xiaoban capsules for the treatment of atherosclerosis based on network pharmacology and analysis of changes to the gut microbiome.Methods. Mice were treated with Guanxin Xiaoban capsules. The 16S rDNA genome sequence of all microorganisms from each group of faecal samples was used to evaluate potential structural changes in the gut microbiota after treatment with Guanxin Xiaoban capsules. Western blotting and real-time quantitative PCR were used to detect gene targets in aortic and liver tissues. Haematoxylin and eosin staining was used to observe improvements in mouse arterial plaques.Results. The gut microbiota of atherosclerotic mice is disturbed. After Guanxin Xiaoban treatment, the abundance of bacteria in the mice improved, with an increase in the proportion of Akkermansia and a significant decrease in the proportion of Faecalibaculum. The main ingredients of Guanxin Xiaoban capsules are calycosin, liquiritin, ferulic acid, ammonium glycyrrhizate, aloe emodin, rhein and emodin. The core genes of this network were determined to be glutathione S-transferase mu 1 (GSTM1), vascular endothelial growth factor A (VEGFA) and cyclin-dependent kinase inhibitor 1A (CDKN1A). The compound-target gene network revealed an interaction between multiple components and targets and contributed to a better understanding of the potential therapeutic effects of the capsules on atherosclerosis. In addition, expression of the AGE-receptor for the AGE (RAGE) pathway was significantly inhibited and the mice showed signs of arterial plaque reduction. Guanxin Xiaoban capsules may improve atherosclerosis and reduce the plaque area by inhibiting the AGE-RAGE signalling pathway to delay the development of atherosclerosis. This mechanism appears to involve changes in the gut microbiota. Therefore, Guanxin Xiaoban capsules have potential value as a treatment for atherosclerosis.

Nano-hydroxyapatite-evoked immune response synchronized with controllable immune adjuvant release for strengthening melanoma-specific growth inhibition.

Concerns about the potential systematic toxicity limit the extensive application of traditional therapeutic drugs for melanoma therapy, nano-hydroxyapatite (nHA) with good biocompatibility and anti-tumor ability could be an alternative choice. In this study, nHA was employed as an anti-tumor biomaterial due to its tumor-specific toxicity. Meanwhile, granulocyte-macrophage colony-stimulating factor (GM-CSF) served as the immune adjuvant to activate the immune response. The delivery platform was fabricated by co-encapsulation of both nHA and GM-CSF into a biocompatible thermosensitive PLGA-PEG-PLGA hydrogel. The results showed that the bio-activities of nHA and GM-CSF could be well-maintained within the hydrogel. Interestingly, the addition of nHA could attenuate the burst release of GM-CSF due to possible protein absorption capacity of nHA, which is beneficial for GM-CSF sustainable release at the tumor site, achieving boosted and prolonged anti-tumor immunity. The in vitro and in vivo data demonstrated that nHA/GM-CSF hydrogel exhibited greater potency to inhibit tumor growth via enhanced CD8+ T-cell response compared with hydrogel and nHA hydrogel groups, contributed by the synergistic effects of nHA and GM-CSF. Overall, the strategy combining nHA and immune adjuvant shows great promise, which largely broadens the choice of combinational therapies for melanoma. STATEMENT OF SIGNIFICANCE: Nano-hydroxyapatite (nHA) has been confirmed to specifically inhibit melanoma tumor growth and induce immune response. However, its antitumor efficiency and immunity-evoking capacity are limited. In this study, granulocyte-macrophage colony-stimulating factor (GM-CSF) was introduced to serve as the immune adjuvant. Both of them were encapsulated into a biocompatible thermosensitive PLGA-PEG-PLGA hydrogel. The addition of nHA could attenuate the burst release of GM-CSF due to the interaction with nHA, which is beneficial for GM-CSF sustainable release at tumor site, achieving boosted and prolonged anti-tumor immunity. Anti-tumor immune response could be activated due to the release of tumor-associated antigen and tumor debris induced by the specifically tumor inhibition effect of nHA and GM-CSF. The combination of nHA and GM-CSF could play synergistic inhibiting effect on tumor growth via boosting and prolonging anti-tumor immunity.

Therapeutic Mechanism of Xiaoqinglong Decoction against COVID-19 Based on Network Pharmacology and Molecular Docking Technology.

BACKGROUND: A xiaoqinglong decoction (XQLD) has been proven effective in treating severe coronavirus disease 2019 (COVID-19) cases; however, the mechanism remains unclear. OBJECTIVE: In the current study, we used network pharmacology and molecular docking technology to identify the effective components, potential targets, and biological pathways of XQLD against COVID-19. METHODS: Public databases were searched to determine the putative targets of the active compounds of XQLD and COVID-19-related targets. STRING and Cytoscape were used to establish the protein-protein interaction network and drug component, along with the target-pathway network. The DAVID database was used to enrich the biological functions and signaling pathways. AutoDock Vina was used for virtual docking. RESULTS: We identified 138 active compounds and 259 putative targets of XQLD. Biological network analysis showed that quercetin, beta-sitosterol, kaempferol, stigmasterol, and luteolin may be critical ingredients of XQLD, whereas VEGFA, IL-6, MAPK3, CASP3, STAT3, MAPK1, MAPK8, CASP8, CCL2, and FOS may be candidate drug targets. Enrichment analysis illustrated that XQLD could function by regulating viral defense, inflammatory response, immune response, and apoptosis. Molecular docking results showed a high affinity between the critical ingredients and host cell target proteins. CONCLUSION: This study uncovered the underlying pharmacological mechanism of XQLD against COVID-19. These findings lay a solid foundation for promoting the development of new drugs against severe acute respiratory syndrome coronavirus-2 infection and may contribute to the global fight against the COVID-19 pandemic.

Use of ATR-FTIR Spectroscopy and Chemometrics for the Variation of Active Components in Different Harvesting Periods of Lonicera japonica.

Lonicera japonica Thunb is a commonly used Chinese herbal medicine, which belongs to the family Caprifoliaceae. The active components varied greatly during bud development. Research on the variation of the main active components is significant for the timely harvesting and quality control of Lonicera japonica. In this study, the attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) combined with the chemometric method was performed to investigate the variability of different harvesting periods of Lonicera japonica. The preliminary characterization from ATR-FTIR fingerprints showed various characteristic absorption peaks of the main active components from the different harvesting times, such as flavonoids, organic acids, iridoids, and volatile oils. Additionally, principal component analysis (PCA) scatter plots showed that there was a clear clustering trend in the samples of the same harvesting period, and the samples of the different harvesting periods could be well distinguished. Finally, further analysis by the orthogonal partial least-squares discriminant analysis (OPLS-DA) showed that there were regular changes in flavonoids, phenolic acids, iridoids, and volatile oils in different harvesting periods. Therefore, ATR-FTIR, as a novel and convenient analytical method, could be applied to evaluate the quality of Lonicera japonica.

Cross-kingdom regulation by dietary plant miRNAs: an evidence-based review with recent updates.

As non-coding RNA molecules, microRNAs (miRNAs) are widely known for their critical role in gene regulation. Recent studies have shown that plant miRNAs obtained through dietary oral administration can survive in the gastrointestinal (GI) tract, enter the circulatory system and regulate endogenous mRNAs. Diet-derived plant miRNAs have 2'-O-methylated modified 3'ends and high cytosine and guanine (GC) content, as well as exosomal packaging, which gives them high stability even in the harsh environment of the digestive system and circulatory system. The latest evidence shows that dietary plant miRNAs can not only be absorbed in the intestine, but also be absorbed and packaged by gastric epithelial cells and then secreted into the circulatory system. Alternatively, these biologically active plant-derived miRNAs may also affect the health of the host by affecting the function of the microbiome, while not need to be taken into the host's circulatory system and transferred to remote tissues. This cross-kingdom regulation of miRNAs gives us hope for exploring their therapeutic potential and as dietary supplements. However, doubts have also been raised about the cross-border regulation of miRNAs, suggesting that technical flaws in the experiments may have led to this hypothesis. In this article, we summarize the visibility of dietary plant miRNAs in the development of human health and recent research data on their use in therapeutics. The regulation of plant miRNAs across kingdoms is a novel concept. Continued efforts in this area will broaden our understanding of the biological role of plant miRNAs and will open the way for the development of new approaches to prevent or treat human diseases.

GC-MS-Based Serum Metabolomic Investigations on the Ameliorative Effects of Polysaccharide from Turpiniae folium in Hyperlipidemia Rats.

Hyperlipidemia, a typical metabolic disorder syndrome, can cause various cardiovascular diseases. The polysaccharides were found to have enormous potential in the therapy of hyperlipidemia. This study was aimed at evaluating the ameliorative effects of polysaccharide from Turpiniae folium (TFP) in rats with hyperlipidemia. A serum metabolomic method based on gas chromatography-mass spectrometry (GC-MS) was used to explore the detailed mechanism of TFP in rats with hyperlipidemia. The oxidative stress indicators, biochemical indexes, and inflammatory factors in serum and histopathological changes in the liver were also evaluated after 10-week oral administration of TFP in rats with high-fat diet-induced hyperlipidemia. TFP significantly relieved oxidative stress, inflammation, and liver histopathology and reduced blood lipid levels. Multivariate statistical approaches such as principal component analysis and orthogonal projection to latent structure square-discriminant analysis revealed clear separations of metabolic profiles among the control, HFD, and HFD+TFP groups, indicating a moderating effect of TFP on the metabolic disorders in rats with hyperlipidemia. Seven metabolites in serum, involved in glycine, serine, and threonine metabolism and aminoacyl-tRNA biosynthesis, were selected as potential biomarkers in rats with hyperlipidemia and regulated by TFP administration. It was concluded that TFP had remarkable potential for treating hyperlipidemia. These findings provided evidence for further understanding of the mechanism of action of TFP on hyperlipidemia.

Quantitative Proteomics Reveal That Metabolic Improvement Contributes to the Cardioprotective Effect of T89 on Isoproterenol-Induced Cardiac Injury.

BACKGROUND: T89, a traditional Chinese medicine, has passed phase II, and is undergoing phase III clinical trials for treatment of ischemic cardiovascular disease by the US FDA. However, the role of T89 on isoproterenol (ISO)-induced cardiac injury is unknown. The present study aimed to explore the effect and underlying mechanism of T89 on ISO-induced cardiac injury. METHODS: Male Sprague-Dawley rats received subcutaneous injection of ISO saline solution at 24 h intervals for the first 3 days and then at 48 h intervals for the next 12 days. T89 at dose of 111.6 and 167.4 mg/kg was administrated by gavage for 15 consecutive days. Rat survival rate, cardiac function evaluation, morphological observation, quantitative proteomics, and Western blotting analysis were performed. RESULTS: T89 obviously improved ISO-induced low survival rate, attenuated ISO-evoked cardiac injury, as evidenced by myocardial blood flow, heart function, and morphology. Quantitative proteomics revealed that the cardioprotective effect of T89 relied on the regulation of metabolic pathways, including glycolipid metabolism and energy metabolism. T89 inhibited the enhancement of glycolysis, promoted fatty acid oxidation, and restored mitochondrial oxidative phosphorylation by regulating Eno1, Mcee, Bdh1, Ces1c, Apoc2, Decr1, Acaa2, Cbr4, ND2, Cox 6a, Cox17, ATP5g, and ATP5j, thus alleviated oxidative stress and energy metabolism disorder and ameliorated cardiac injury after ISO. The present study also verified that T89 significantly restrained ISO-induced increase of HSP70/HSP40 and suppressed the phosphorylation of ERK, further restored the expression of CX43, confirming the protective role of T89 in cardiac hypertrophy. Proteomics data are available via ProteomeXchange with identifier PXD024641. CONCLUSION: T89 reduced mortality and improves outcome in the model of ISO-induced cardiac injury and the cardioprotective role of T89 is correlated with the regulation of glycolipid metabolism, recovery of mitochondrial function, and improvement of myocardial energy.