Fuzheng Huayu recipe inhibits bleomycin-induced pulmonary fibrosis in rats by inhibiting M2 polarization of macrophages via the oxidative phosphorylation pathway.

Fuzheng Huayu recipe (FZHYR) is a Chinese patent medicine for the treatment of fibrosis. The effects of FZHYR on pulmonary fibrosis and macrophage polarization were investigated in vitro. FZHYR inhibited pulmonary inflammation and fibrosis and M2 polarization of macrophages in bleomycin-induced pulmonary fibrosis (BPF) of rat model. Differentially expressed genes were screened by high-throughput mRNA sequencing and GSEA showed that oxidative phosphorylation (OXPHOS) was correlated with BPF. FZHYR inhibited expressions of Ndufa2 and Ndufa6 in lung tissues of BPF rats. These findings suggest that OXPHOS pathway serves as a possible target for pulmonary fibrosis therapy by FZHYR.

Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. METHODS: A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg- 1), curcumin (Cur, 40 mg·kg- 1) and metformin (Met, 50 mg·kg- 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml- 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. RESULTS: The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. CONCLUSION: NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.

Successful secukinumab treatment of generalized pustular psoriasis.

Generalized pustular psoriasis is a rare variant of psoriasis. Evidence recommending generalized pustular psoriasis treatment with secukinumab is limited. This report aims to evaluate the use of secukinumab in two patients with generalized pustular psoriasis. The standard treatment regimen for secukinumab was as follows: 300mg subcutaneously once weekly in weeks 0-4, followed by 300mg every four weeks. The efficacy was evaluated by analyzing the psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). One patient had generalized pustular psoriasis, which had developed from palmoplantar pustulosis over 12 years. The second patient was an adolescent with recurrent generalized pustular psoriasis. The first patient achieved PASI-75 response by week 3 and both PASI-90 and a DLQI score of 0 were observed by week 8. The second patient achieved PASI-75 response by week 4 and complete clinical resolution, except for nail changes, and a DLQI of 0 by week 8, without any adverse events.

[Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative].

The protection, development, and utilization of medicinal plant resources are important cornerstones of maintaining human health. However, due to factors such as the reduction of high-quality land resources, deterioration of ecological environments, and excessive and disorderly resource development, medicinal plant resources are becoming scarce, and some of them are insufficiently supplied. With the proposal of "the Belt and Road" Initiative, the cooperation between China and "the Belt and Road" partners(the countries and regions involved in "the Belt and Road" Initiative)is increasingly close, which provides a new opportunity for carrying out trade of medicinal plant resources and alleviating the problem of imbalance and relative inadequacy of medicinal plant resources in countries. This study first determined the distribution and species information of plant resources in countries and regions involved in "the Belt and Road" Initiative by investigating the database of plant distribution and that of medicinal plant resources. Then, according to the published data from the International Union for Conservation of Nature(IUCN) and the Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), this study identified the rare and endangered medicinal plants and the medicinal plants under trade control in countries and regions involved in "the Belt and Road" Initiative and finally sorted out the list of potential medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative that can be used by China. This data resource can not only be used for the overall protection of important endangered species but also scientifically guide the development and utilization of medicinal resources, providing guidance and a theoretical basis for the sustainable development of medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative.

Mechanistic insights into the selectivity of bicyclophosphorothionate antagonists for housefly versus rat GABA receptors.

BACKGROUND: γ-Aminobutyric acid (GABA) receptors (GABARs) are validated targets of insecticides. Bicyclophosphorothionates are a group of insecticidal compounds that act as noncompetitive antagonists of GABARs. We previously reported that the analogs exhibit various degrees of selectivity for housefly versus rat GABARs, depending on substitutions at the 3- and 4-positions. We here sought to elucidate the unsolved mechanisms of the receptor selectivity using quantitative structure-activity relationship (QSAR), molecular docking, and molecular dynamics approaches. RESULTS: Three-dimensional (3D)-QSAR studies using Topomer comparative molecular field analysis quantitatively demonstrated how the introduction of a small alkyl group at the 3-position of bicyclophosphorothionates contributes to the housefly versus rat GABAR selectivity. To investigate the molecular mechanisms of the selective action, bicyclophosphorothionates were docked into housefly Resistance to dieldrin (RDL) GABAR and rat α1ß2γ2 GABAR homology models built using the published 3D-structures of human GABARs as templates. The results of molecular docking and molecular dynamics simulations revealed that the 2'Ala and 6'Thr residues of the RDL subunit within the channel are the key amino acids for binding to the housefly GABARs, whereas the 2'Ser residue of γ2 subunit plays a crucial role in binding to rat GABARs. CONCLUSION: We revealed the molecular mechanisms underlying the selective antagonistic action of bicyclophosphorothionates on housefly versus rat GABARs. The information presented should help design and develop novel, safe GABAR-targeting insecticides. © 2023 Society of Chemical Industry.

Identification of survival-associated biomarkers based on three datasets by bioinformatics analysis in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors with poor prognosis in terms of advanced stage. However, the survival-associated biomarkers for GC remains unclear. AIM: To investigate the potential biomarkers of the prognosis of patients with GC, so as to provide new methods and strategies for the treatment of GC. METHODS: RNA sequencing data from The Cancer Genome Atlas (TCGA) database of STAD tumors, and microarray data from Gene Expression Omnibus (GEO) database (GSE19826, GSE79973 and GSE29998) were obtained. The differentially expressed genes (DEGs) between GC patients and health people were picked out using R software (x64 4.1.3). The intersections were underwent between the above obtained co-expression of differential genes (co-DEGs) and the DEGs of GC from Gene Expression Profiling Interactive Analysis database, and Gene Ontology (GO) analysis, Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA), Protein-protein Interaction (PPI) analysis and Kaplan-Meier Plotter survival analysis were performed on these DEGs. Using Immunohistochemistry (IHC) database of Human Protein Atlas (HPA), we verified the candidate Hub genes. RESULTS: With DEGs analysis, there were 334 co-DEGs, including 133 up-regulated genes and 201 down-regulated genes. GO enrichment analysis showed that the co-DEGs were involved in biological process, cell composition and molecular function pathways. KEGG enrichment analysis suggested the co-DEGs pathways were mainly enriched in ECM-receptor interaction, protein digestion and absorption pathways, etc. GSEA pathway analysis showed that co-DEGs mainly concentrated in cell cycle progression, mitotic cell cycle and cell cycle pathways, etc. PPI analysis showed 84 nodes and 654 edges for the co-DEGs. The survival analysis illustrated 11 Hub genes with notable significance for prognosis of patients were screened. Furtherly, using IHC database of HPA, we confirmed the above candidate Hub genes, and 10 Hub genes that associated with prognosis of GC were identified, namely BGN, CEP55, COL1A2, COL4A1, FZD2, MAOA, PDGFRB, SPARC, TIMP1 and VCAN. CONCLUSION: The 10 Hub genes may be the potential biomarkers for predicting the prognosis of GC, which can provide new strategies and methods for the diagnosis and treatment of GC.

A study evaluating liquid-based endometrial cytology test and transvaginal ultrasonography as a screening tool for endometrial cancer in 570 postmenopausal women.

OBJECTIVE: To evaluate the combination of transvaginal ultrasonography (TVS) and endometrial cytology test (ECT) as a potential diagnostic strategy for endometrial cancer and endometrial precancerous lesions in postmenopausal patients. METHODS: 570 postmenopausal patients admitted in our hospital due to abnormal bleeding or other symptoms and/or with endometrium thickness over 5 mm on ultrasound. The endometrial thickness was evaluated by TVS. Following obtainment with written consent, all patients underwent ECT, hysteroscopy and then dilatation and curettage (D&C). Cytological sampling was conducted by scratching the uterus cavity using SAP-1 and the samples were prepared as liquid-based smear using SurePath technology. The samples were stained using Papanicolaou method. The correlation between cytological diagnosis and TVS results with the D&C histological diagnosis was analyzed. The WHO classification was used for diagnosis. RESULTS: Sensitivity of ECT, TVS, ECT or TVS positive, ECT and TVS positive to diagnose atypical hyperplasia or worse were estimated at 80.7%, 86.8%, 97.4%, 70.2%, specificity at 94.7%, 20.4%, 17.5%, 88.4%, positive predictive value at 58.2%, 21.1%, 22.8%, 60.2%, negative predictive value at 94.4%, 86.1%, 96.4%, 92.2%, and accuracy at 84.6%, 33.7%, 33.5%, 84.7%, respectively. CONCLUSIONS: Transvaginal ultrasonography and Endometrial cytology test may be regarded as a effective first-line method in endometrial pathology detection in postmenopausal women.

Construction and Identification of an NLR-Associated Prognostic Signature Revealing the Heterogeneous Immune Response in Skin Cutaneous Melanoma.

Background: Skin cutaneous melanoma (SKCM) is the deadliest dermatology tumor. Ongoing researches have confirmed that the NOD-like receptors (NLRs) family are crucial in driving carcinogenesis. However, the function of NLRs signaling pathway-related genes in SKCM remains unclear. Objective: To establish and identify an NLRs-related prognostic signature and to explore its predictive power for heterogeneous immune response in SKCM patients. Methods: Establishment of the predictive signature using the NLRs-related genes by least absolute shrinkage and selection operator-Cox regression analysis (LASSO-COX algorithm). Through univariate and multivariate COX analyses, NLRs signature's independent predictive effectiveness was proven. CIBERSORT examined the comparative infiltration ratios of 22 distinct types of immune cells. RT-qPCR and immunohistochemistry implemented expression validation for critical NLRs-related prognostic genes in clinical samples. Results: The prognostic signature, including 7 genes, was obtained by the LASSO-Cox algorithm. In TCGA and validation cohorts, SKCM patients with higher risk scores had remarkably poorer overall survival. The independent predictive role of this signature was confirmed by multivariate Cox analysis. Additionally, a graphic nomogram demonstrated that the risk score of the NLRs signature has high predictive accuracy. SKCM patients in the low-risk group revealed a distinct immune microenvironment characterized by the significantly activated inflammatory response, interferon-α/γ response, and complement pathways. Indeed, several anti-tumor immune cell types were significantly accumulated in the low-risk group, including M1 macrophage, CD8 T cell, and activated NK cell. It is worth noting that our NLRs prognostic signature could serve as one of the promising biomarkers for predicting response rates to immune checkpoint blockade (ICB) therapy. Furthermore, the results of expression validation (RT-qPCR and IHC) were consistent with the previous analysis. Conclusion: A promising NLRs signature with excellent predictive efficacy for SKCM was developed.

Stepwise Asymmetric Allylic Substitution-Isomerization Enabled Mimetic Synthesis of Axially Chiral B,N-Heterocycles.

Axially chiral molecules bearing multiple stereogenic axes are of great importance in the field of organic chemistry. However, the efficient construction of atropisomers featuring two different types of stereogenic axes has rarely been explored. Herein, we report the novel atroposelective synthesis of configurationally stable axially chiral B,N-heterocycles. By using stepwise asymmetric allylic substitution-isomerization (AASI) strategy, diaxially chiral B,N-heterocycles bearing B-C and C-N axes that are related to the moieties of axially chiral enamines and arylborons were also obtained. In this case, all four stereoisomers of diaxially chiral B,N-heterocycles were stereodivergently afforded in high enantioselectivities. Density functional theory (DFT) studies demonstrated that the NH⋅⋅⋅π interactions played a unique role in the promotion of stereospecific isomerization, thereby leading to the highly efficient central-to-axial chirality transfer.

Sanguinarine protects against indomethacin-induced small intestine injury in rats by regulating the Nrf2/NF-κB pathways.

In recent years, small intestine as a key target in the treatment of Inflammatory bowel disease caused by NSAIDs has become a hot topic. Sanguinarine (SA) is one of the main alkaloids in the Macleaya cordata extracts with strong pharmacological activity of anti-tumor, anti-inflammation and anti-oxidant. SA is reported to inhibit acetic acid-induced colitis, but it is unknown whether SA can relieve NSAIDs-induced small intestinal inflammation. Herein, we report that SA effectively reversed the inflammatory lesions induced by indomethacin (Indo) in rat small intestine and IEC-6 cells in culture. Our results showed that SA significantly relieved the symptoms and reversed the inflammatory lesions of Indo as shown in alleviation of inflammation and improvement of colon macroscopic damage index (CMDI) and tissue damage index (TDI) scores. SA decreased the levels of TNF-α, IL-6, IL-1ß, MDA and LDH in small intestinal tissues and IEC-6 cells, but increased SOD activity and ZO-1 expression. Mechanistically, SA dose-dependently promoted the expression of Nrf2 and HO-1 by decreasing Keap-1 level, but inhibited p65 phosphorylation and nuclear translocation in Indo-treated rat small intestine and IEC-6 cells. Furthermore, in SA treated cells, the colocalization between p-p65 and CBP in the nucleus was decreased, while the colocalization between Nrf2 and CBP was increased, leading to the movement of gene expression in the nucleus to the direction of anti-inflammation and anti-oxidation. Nrf2 silencing blocked the effects of SA. Together our results suggest that SA can significantly prevent intestinal inflammatory lesions induced by Indo in rats and IEC-6 cells through regulation of the Nrf2 pathway and NF-κBp65 pathway.

Green synthesis, structure optimization and biological evalution of Rhopaladins' analog 2-styryl-5-oxopyrrolidine-2- carboxamide RPDPRH on CaSki cells.

We have synthesized Rhopaladins' analog (2E,4E)-4-chlorobenzylidene-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) via a highly facile, inexpensive and green approach and verified the structural superiority of compound RPDPRH through molecular docking. Moreover, we further detected the anti-proliferation, apoptosis and HPV E6/E7 effects of RPDPRH on CaSki cells. Finally, we confirmed that compared with the previous compound (E)-N-(tert-butyl)-2-(4-chlorobenzoyl)-4-(4-fluorobenzylidene)-1-isopropyl-5-oxopyrrolidine-2-carboxamide (RPDPB), RPDPRH could better inhibit proliferation, induce apoptosis, and down-regulate HPV E6/E7 mRNA expression on Caski cells. And preliminary RT-PCR experiments have demonstrated that RPDPRH also could affect the expression of Bcl-2, Bax and Caspase-3 mRNA in Caski cells. In summary, RPDPRH has potential as an effective agent against cervical cancer and will play an important role in our subsequent research.

Hypopigmented Mycosis Fungoides: A Clinicopathological Review of 32 Patients.

Background: Hypopigmented mycosis fungoides (hMF) is gradually acknowledged by more dermatologists, yet a consensus regarding its characteristics is not reached. The profile of Chinese hMF patients has not been deeply reviewed previously. Our research may contribute to the understanding of hMF, especially the Chinese patients with Fitzpatrick phototypes of III and IV. Aim: To have a better understanding of hMF in terms of clinical, histopathological and immunohistochemical features in the Chinese population and to determine if there are differences between the Chinese population and other ethnic groups. Methods: We made a retrospective analysis of clinical, histopathological and immunohistochemical features of 32 hMF patients in our hospital from 2010 to 2020. These features were then summarized and compared with previous reports. Results: All patients belonged to Fitzpatrick phototypes of III or IV. Twenty-one male (65.63%) patients and 11 female (34.37%) patients were analyzed, and the male to female ratio was 1.9:1. The age at diagnosis of patients ranged from 4 to 39 years, and the average age at diagnosis of these patients was 18 years, the median age was 16.5. Back was the most frequent site (34.37%). The clinical and histological results of lesions had no distinctive points. Immunohistochemically, among these 32 patients, there were 30 patients whose information was complete, there was 19 patients (63.33%) who were CD8 positive lymphocytes predominance, 9 patients (30%) had CD8 and CD4 positive lymphocyte mixed infiltration, and other 2 patients (6.67%) had CD4 positive lymphocytes predominance. Partial loss of CD7 was only observed in 1 patient (3.33%). Nearly all patients adopted topical nitrogen mustard and topical steroid and most of them had an excellent prognosis. Conclusion: The clinical profiles of hMF in Chinese population shared differences with other ethnic groups, but its histopathological, immunohistochemical results and prognosis condition were resembled with other previous reports. Hence, more patients were needed to find the characteristics of hMF.

miR167d-ARFs Module Regulates Flower Opening and Stigma Size in Rice.

Flower opening and stigma exertion are two critical traits for cross-pollination during seed production of hybrid rice (Oryza sativa L.). In this study, we demonstrate that the miR167d-ARFs module regulates stigma size and flower opening that is associated with the elongation of stamen filaments and the cell arrangement of lodicules. The overexpression of miR167d (OX167d) resulted in failed elongation of stamen filaments, increased stigma size, and morphological alteration of lodicule, resulting in cleistogamy. Blocking miR167d by target mimicry also led to a morphological alteration of the individual floral organs, including a reduction in stigma size and alteration of lodicule cell morphology, but did not show the cleistogamous phenotype. In addition, the four target genes of miR167d, namely ARF6, ARF12, ARF17, and ARF25, have overlapping functions in flower opening and stigma size. The loss-of-function of a single ARF gene did not influence the flower opening and stigma size, but arf12 single mutant showed a reduced plant height and aborted apical spikelets. However, mutation in ARF12 together with mutation in either ARF6, ARF17, or ARF25 led to the same defective phenotypes that were observed in OX167d, including the failed elongation of stamen filaments, increased stigma size, and morphological alteration of lodicule. These findings indicate that the appropriate expression of miR167d is crucial and the miR167d-ARFs module plays important roles in the regulation of flower opening and stigma size in rice.

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.

Brønsted acid-enhanced copper-catalyzed atroposelective cycloisomerization to axially chiral arylquinolizones via dearomatization of pyridine.

The construction of axially chiral N-heterobiaryls is of great interest as a result of their occurrence in organocatalysts, chiral ligands, natural products, and biologically active molecules. Despite remarkable achievements in this area, strategies for the preparation of new classes of axially chiral N-heterobiaryls remain to be further explored. Herein, we report the enantioselective synthesis of axially chiral arylquinolizones through an intramolecular atroposelective cycloisomerization. The reaction proceeds via the Brønsted acid-enhanced dearomatization of pyridine by a copper catalyst that allows for the formation of the desired products in excellent yields and enantioselectivities. The utility of this methodology is illustrated by a synthesis on gram scale production and transformation of the products into chiral thiourea catalysts. Mechanistic studies demonstrate that Brønsted acid plays a significant role in promoting the reactivity of the reaction, while both the steric and electronic effects of aryl substituents in substrate play a role in controlling the stereoselectivity.

A network pharmacology approach to investigate the anticancer mechanism of cinobufagin against hepatocellular carcinoma via downregulation of EGFR-CDK2 signaling.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers with high mortality and poor prognosis, and the investigation on new approaches and effective drugs for HCC therapy is of great significance. In our study, we demonstrate that treatment with cinobufagin, a natural compound isolated from traditional chinese medicine Chansu, reduces proliferation and the colony formation capacity of the human hepatoma cells in vitro, in addition, cinobufagin induces mitotic arrest in human hepatoma cells. The results of a network pharmacology-based analysis show that EGFR, MAPK1, PTK2, CDK2, MAPK3, ESR1, CDK1, PRKCA, AR, and CSNK2A1 are the key targets involved in the anti-tumor activities of cinobufagin, additionally, several signaling pathways such as proteoglycans in cancer, pathways in cancer, HIF-1 signaling pathway, VEGF signaling pathway, ErbB signaling pathway, and PI3K-AKT signaling pathway are identified as the potential pathways involved in the inhibitory effects of cinobufagin against HCC. Furthermore, at the molecular level, we find that cinobufagin decreases EGFR expression and CDK2 activity in human hepatoma cells. Inhibition of EGFR or CDK2 expression could not only suppress the growth of tumor cells but also enhance the inhibitory effects of cinobufagin on the proliferative potential of human hepatoma cells. We also demonstrate that EGFR positively regulates CDK2 expression. Furthermore, EGFR inhibitor gefitinib or CDK2 inhibitor CVT-313 synergistically enhances anticancer effects of cinobufagin in human hepatoma cells. Taken together, these findings indicate that cinobufagin may exert antitumor effects by suppressing EGFR-CDK2 signaling, and our study suggests that cinobufagin may be a novel, promising anticancer agent for the treatment of HCC.

Corrigendum: The Role of High-Content Complex Dietary Fiber in Medical Nutrition Therapy for Gestational Diabetes Mellitus.

[This corrects the article DOI: 10.3389/fphar.2021.684898.].

Identification of the Role of Wnt/ß-Catenin Pathway Through Integrated Analyses and in vivo Experiments in Vitiligo.

PURPOSE: Vitiligo is an acquired depigmentation skin disease, which affects an average of 1% of the world's population. The purpose of this study is to identify the key genes and pathways responsible for vitiligo and find new therapeutic targets. METHODS: The datasets GSE65127, GSE53146, and GSE75819 were downloaded from the Gene Expression Omnibus (GEO) database. R language was used to identify the differentially expressed genes (DEGs) between lesional skin of vitiligo and non-lesional skin. Next, the key pathways were obtained by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The protein-protein interaction (PPI) networks were conducted by STRING database and Cytoscape software. Subsequently, module analysis was performed by Cytoscape. Among these results, the Wnt/ß-catenin pathway and melanogenesis pathway caught our attention. The expression level of ß-catenin, microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) was detected by immunofluorescence in vitiligo lesions and healthy skin. Moreover, zebrafish was treated with XAV-939, an inhibitor of the Wnt/ß-catenin pathway. After that, the area of melanin granules as a percentage of the head area was measured. The mRNA expression of ß-catenin, lymphoid-enhancing factor 1(lef1), tyr and mitf were detected by q-PCR (quantitative polymerase chain reaction) in zebrafish (Danio rerio). RESULTS: A total of 2442 DEGs were identified, including 1068 upregulated and 1374 downregulated DEGs. The key pathways were identified by GO and KEGG analyses, such as "NOD-like receptor signaling pathway", "Wnt signaling pathway", "Melanogenesis", "mTOR signaling pathway", "PI3K-Akt signaling pathway", "Calcium signaling pathway" and "Rap1 signaling pathway". The immunofluorescence results showed that the level of ß-catenin, MITF and TYR was significantly downregulated in vitiligo lesional skin. In zebrafish, the mean percentage area of melanin granules and the expression of ß-catenin, lef1, tyr and mitf were decreased after treated with XAV-939. CONCLUSION: The present study identified key genes and signaling pathways associated with the pathophysiology of vitiligo. Among them, the Wnt/ß-catenin pathway played an essential role in pigmentation and could be a breakthrough point in vitiligo treatment.

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.