ent-Kaurane diterpenoids from Isodon henryi and their anti-inflammatory activities.

Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudô afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C-K (1-9). Compounds 1-6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2-6 all contained a free α-methylene-γ-carboxylic acid. Compound 6 was also a rare 6,8-cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu Kα) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC50 values of 15.99 ± 0.75 and 18.19 ± 0.42 µM, respectively.

Exploring the potential mechanisms of the ethyl acetate fraction of Hippophae rhamnoides L. seeds as a natural healing agent for wound repair.

ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides L.) has been designated a "medicine food homology" fruit by the National Health Commission of China due to its nutritional value. In traditional Chinese ethnomedicine, Hippophae rhamnoides L. is commonly used to treat nonhealing wounds such as burns, sores, and gastric ulcers. The aim of this study was to explore the healing effects of the ethyl acetate extract of sea buckthorn seeds (SBS-EF) on burn wounds. AIM OF THE STUDY: The primary objectives of this research were to determine the most effective medicinal site of action for treating burns with sea buckthorn seeds (SBS) and to investigate the underlying material basis and mechanisms of their therapeutic effects. MATERIALS AND METHODS: The effects of different components of SBS-EF on the proliferation and migration of human skin fibroblasts (HSFs) were evaluated via MTT assays, scratch assays, transwell assays, and hydroxyproline secretion analysis. SBS-EF displayed the greatest activity amongst the extracts. Subsequent analyses included network pharmacology methodology, molecular docking studies, ultraperformance liquid chromatography UPLC-Orbitrap-Exploris-120-MS and a severe second-degree burn rat model to investigate the chemical constituents and potential therapeutic mechanisms of the SBS-EF. RESULTS: In vitro studies demonstrated the efficacy of SBS-EF in promoting HSF growth and migration. UPLC-Orbitrap-Exploris-120-MS analysis revealed that SBS-EF had ten major constituents, with flavonoids being the predominant compounds, especially catechin, quercetin, and kaempferol derivatives. Network pharmacology and molecular docking analyses indicated that SBS-EF may exert its healing effects by modulating the Wnt/ß-catenin signalling pathway. Subsequent in vivo experiments demonstrated that SBS-EF accelerated burn wound healing in rats, increased hydroxyproline expression in skin tissue, facilitated skin structure repair, and enhanced collagen production and organisation over a 21 d period. Additionally, exposure to SBS-EF upregulated WNT3a and ß-catenin while downregulating GSK-3ß levels in rat skin tissue. CONCLUSIONS: The wound healing properties of SBS-EF were attributed to its ability to enhance HSF growth and migration, increase hydroxyproline levels in the skin, promote collagen accumulation, reduce scarring, and decrease the skin water content. SBS-EF may also provide therapeutic benefits for burns by modulating the Wnt/ß-catenin signalling pathway, as evidenced by its effective site and likely mechanism of action in the treatment of burned rats.

Revealing the effects and mechanism of wine processing on Corni Fructus using chemical characterization integrated with multi-dimensional analyses.

Corni fructus (CF) is always subjected to wine processing before prescription in clinic, for an enhancing effect of nourishing liver and kidney. While, the underlying mechanism for this processing on CF remains obscure. In this study, a sensitive ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method combined multi-dimensional analyses was established to monitor chemical characterizations of raw and wine-processed CF (WCF) and hence reveal the effects and underlying mechanism of wine processing on CF. As indicated, a total of 216 compounds were tentatively identified, including 98 structurally complex and variable home/hetero-polymers, that were composed of iridoid glucosides, gallic acids, caffeic acid and/or 5-HMF. Interestingly, 53 of these compounds probably characterized potential novel, including 35 iridoid glucosides or their dimers, 9 iridoid glucoside-gallic acid dimers, 7 gallic acids derivatives and 2 gallic acid-caffeic acid dimers, which provides ideas for natural product researchers. Meanwhile, the multi-dimensional analyses including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear regression analysis were used to explore the differences between CF and WCF. The results showed that 23 compounds as chemical markers greatly contributing to the distinction were screened out, and 3 of which (7α/ß-O-ethyl-morroniside, gallic acid and 5-HMF) in WCF indicated an increasing trend in intensities in relative to those in CF. Additionally, linear regression analysis showed that in WCF 53 compounds exhibited an increasing in intensities, while 132 ones did a decreasing trend, compared with those in CF. As our investigation demonstrated, acetal reaction of morroniside, ester hydrolysis in different organic acid derivatives as well as glycoside bond cleavage during wine processing probably resulted in the distinctions. The findings of this study provide a further understanding of the effect and mechanism of wine processing on CF.

Diarylheptanoid glycosides from Dioscorea nipponica rhizomes.

A group of previously undescribed diarylheptanoids with mono/di-glucose substitution, diodiarylheptosides A-F (1-6), together with six known diarylheptanoids (7-12) were isolated from the rhizomes of Dioscorea nipponica. Their structures were established by comprehensive UV, IR, HR-ESI-MS and NMR analyses, and their absolute configurations were determined by a comparison of calculated and experimental ECD, some with optical rotations, after acid-hydrolysis. Moreover, bioassay results showed that compounds 3 and 11 exhibited stronger NO inhibitions on lipopolysaccharides-induced RAW 264.7 cells, with the IC50 values of 14.91 ± 0.62 and 12.78 ± 1.12 µM.

Syntaxin6 contributes to hepatocellular carcinoma tumorigenesis via enhancing STAT3 phosphorylation.

BACKGROUND: Syntaxin6 (STX6) is a SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein complex located in the trans-Golgi network and endosomes, which is closely associated with a variety of intracellular membrane transport events. STX6 has been shown to be overexpressed in a variety of human malignant tumors such as esophageal, colorectal, and renal cell carcinomas, and participates in tumorigenesis and development. METHODS: Based on clinical public database and clinical liver samples analysis, the expression of STX6 in hepatocellular carcinoma (HCC) tissues was investigated. The effects of STX6 on proliferation, migration and invasion of HCC cell in vitro and in vivo were evaluated through gain- and loss-of-function studies. We further performed RNA-seq analysis and protein interactome analysis, to further decifer the detailed mechanisms of STX6 in the regulation of the JAK-STAT pathway in HCC. RESULTS: STX6 expression was upregulated in HCC tissues and its expression was highly correlated with the high histological grade of the tumor. STX6 promoted HCC cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, STX6 mediated tumor progression depending on promoting the activation of JAK-STAT signaling pathway. Receptor for activated protein kinase C (RACK1) as an essential adaptor protein mediating STX6 regulation of JAK-STAT pathway. Specifically, STX6 interacted with RACK1 and then recruited signal transducer and activator of transcription 3 (STAT3) to form a protein-binding complex and activates STAT3 transcriptional activity. CONCLUSIONS: This study provided a novel concept that STX6 exerted oncogenic effects by activating the STAT3 signaling pathway, and STX6 might be a promising therapeutic target for HCC.

Anti-inflammatory lindenane sesquiterpenoid dimers from the roots of Chloranthus holostegius var. trichoneurus.

Two new lindenane-type sesquiterpenoid dimers, chlotrichenes C and D (1 and 2) together with five known lindenane-type sesquiterpenoid dimers (3-7) were isolated from the roots of Chloranthus holostegius var. trichoneurus, a famous natural medicine named as "Sikuaiwa" for subduing swellings and relieving pain. The structures including absolute configuration were elucidated by their 1D and 2D NMR, HRESIMS, and ECD data. Compounds 1 and 2 were classical [4 + 2] lindenane-type sesquiterpenoid dimers that differed from known analogs in oxidation profile, side chain profile, and double bond position. The new isolates and compound 3 exhibited significant inhibitory activity on IL-1ß production (IC50: 1-15 µM) in LPS-induced THP-1 cells and other compounds exhibited inhibitory activity on NO production in LPS-induced RAW 264.7 cells (IC50: 24-33 µM).

Factors affecting local alveolar bone thickness in unilateral maxillary canine-lateral incisor transposition.

INTRODUCTION: This study aimed to use 3-dimensional data to investigate the factors affecting local alveolar bone thickness in unilateral maxillary canine-lateral incisor transposition. METHODS: Pretreatment cone-beam computed tomography data of 34 patients with unilateral maxillary canine-lateral transposition were imported into Dolphin Imaging software (version 11.8; Dolphin Imaging and Management Solutions, Chatsworth, Calif) for 3-dimensional reconstruction. The age, gender, and type of transposition at the beginning of treatment were recorded. The thickness and height of the transposed canine, the labiopalatal and distomedial distance from the transposed canine to the apex of the lateral incisor, the inclination of the transposed lateral incisor, the apical height of the lateral incisor, and the alveolar bone thickness in the apical plane were measured. Multiple linear regression analyses were applied to investigate the factors affecting alveolar bone thickness in the apical plane of the transposed lateral incisor. Two sample t test were applied to assess the difference of alveolar bone thickness in patients of different ages. RESULTS: The 10 boys and 24 girls had a mean age of 12.26 ± 2.34 years. In all 34 participants, the apical alveolar bone thickness of transposed lateral incisors was significantly higher than that of the unaffected side (P <0.05). Based on multiple regression analyses, factors associated with a wider alveolar bone thickness were as follows: age (ß = -0.237; P = 0.008), the labiopalatal distance from the transposed canine to the apex of the lateral incisor (ß = 0.675; P <0.001), and the inclination of the transposed lateral incisor (ß = 0.048; P = 0.032). Patients aged <11 years had significantly thicker alveolar bone than that of patients aged >11 years (P <0.05). CONCLUSIONS: Patients with younger age, greater lateral incisor inclination, and greater labiopalatal distance between canine and lateral incisor had more alveolar bone thickness. Early treatment permits tooth movement within the thicker alveolar bone.

Spem2, a novel testis-enriched gene, is required for spermiogenesis and fertilization in mice.

Spermiogenesis is considered to be crucial for the production of haploid spermatozoa with normal morphology, structure and function, but the mechanisms underlying this process remain largely unclear. Here, we demonstrate that SPEM family member 2 (Spem2), as a novel testis-enriched gene, is essential for spermiogenesis and male fertility. Spem2 is predominantly expressed in the haploid male germ cells and is highly conserved across mammals. Mice deficient for Spem2 develop male infertility associated with spermiogenesis impairment. Specifically, the insufficient sperm individualization, failure of excess cytoplasm shedding, and defects in acrosome formation are evident in Spem2-null sperm. Sperm counts and motility are also significantly reduced compared to controls. In vivo fertilization assays have shown that Spem2-null sperm are unable to fertilize oocytes, possibly due to their impaired ability to migrate from the uterus into the oviduct. However, the infertility of Spem2-/- males cannot be rescued by in vitro fertilization, suggesting that defective sperm-egg interaction may also be a contributing factor. Furthermore, SPEM2 is detected to interact with ZPBP, PRSS21, PRSS54, PRSS55, ADAM2 and ADAM3 and is also required for their processing and maturation in epididymal sperm. Our findings establish SPEM2 as an essential regulator of spermiogenesis and fertilization in mice, possibly in mammals including humans. Understanding the molecular role of SPEM2 could provide new insights into future therapeutic treatment of human male infertility and development of non-hormonal male contraceptives.

An ethanolic extract of Arctium lappa L. leaves ameliorates experimental atherosclerosis by modulating lipid metabolism and inflammatory responses through PI3K/Akt and NF-κB singnaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS), a lipid-induced inflammatory condition of the arteries, is a primary contributor to atherosclerotic cardiovascular diseases including stroke. Arctium lappa L. leaf (ALL), an edible and medicinal herb in China, has been documented and commonly used for treating stroke since the ancient times. However, the elucidations on its anti-AS effects and molecular mechanism remain insufficient. AIM OF THE STUDY: To investigate the AS-ameliorating effects and the underlying mechanism of action of an ethanolic extract of leaves of Arctium lappa L. (ALLE). MATERIALS AND METHODS: ALLE was reflux extracted using with 70% ethanol. An HPLC method was established to monitor the quality of ALLE. High fat diet (HFD) and vitamin D3-induced experimental AS in rats were used to determine the in vivo effects; and oxidized low-density lipoprotein-induced RAW264.7 macrophage foam cells were used for in vitro assays. Simvatatin was used as positive control. Biochemical assays were implemented to ascertain the secretions of lipids and pro-inflammatory mediators. Haematoxylin-eosin (H&E) and Oil red O stains were employed to assess histopathological alterations and lipid accumulation conditions, respectively. CCK-8 assays were used to measure cytotoxicity. Immunoblotting assay was conducted to measure protein levels. RESULTS: ALLE treatment significantly ameliorated lipid deposition and histological abnormalities of aortas and livers in AS rats; improved the imbalances of serum lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C); notably attenuated serum concentrations of inflammation-associated cytokines/molecules including TNF-α, IL-6, IL-1ß, VCAM-1, ICAM-1and MMP-9. Mechanistic studies demonstrated that ALLE suppressed the phosphorylation/activation of PI3K, Akt and NF-κB in AS rat aortas and in cultured foam cells. Additionally, the PI3K agonist 740Y-P notably reversed the in vitro inhibitory effects of ALLE on lipid deposition, productions of TC, TNF-α and IL-6, and protein levels of molecules of PI3K/Akt and NF-κB singnaling pathways. CONCLUSIONS: ALLE ameliorates HFD- and vitamin D3-induced experimental AS by modulating lipid metabolism and inflammatory responses, and underlying mechanisms involves inhibition of the PI3K/Akt and NF-κB singnaling pathways. The findings of this study provide scientific justifications for the traditional application of ALL in managing atherosclerotic diseases.

[Two new phenylpropanoids from wine-processed Corni Fructus].

Six compounds were isolated from aqueous extract of wine-processed Corni Fructus through silica gel, ODS column chromatography, Sephadex LH-20 gel column chromatography, reverse phase preparative HPLC and other chromatographic separation technologies. Their structures were identified with multiple spectroscopical methods including HR-ESI-MS, UV, IR, NMR and ECD and so on. Their structures were established as pinoresinoside B(1), cornusgallicacid A(2),(+)-isolariciresinol-9'-O-ß-glucopyranoside(3),(-)-isolariciresinol 3α-O-ß-D-glucopyranoside(4),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucopyranoside(5), and(-)-seco isolariciresinol-9'-O-ß-D-glucopyranoside(6). Among them, compounds 1 and 2 were two new compounds. The biological activity evaluation results showed that compounds 2 and 6 had strong DPPH free radical scavenging ability, with EC_(50) values of(4.18±1.96) and(21.45±1.19) µmol·L~(-1), respectively. Compounds 1 and 2 had protective effects on H_2O_2-induced oxidative damage in NRK-52E cells in a dose-dependent manner, and the cell survival rate of compound 2 at 100 µmol·L~(-1) was 96.09%±1.77%.

Chemically induced revitalization of damaged hepatocytes for regenerative liver repair.

In prolonged liver injury, hepatocytes undergo partial identity loss with decreased regenerative capacity, resulting in liver failure. Here, we identified a five compound (5C) combination that could restore hepatocyte identity and reverse the damage-associated phenotype (e.g., dysfunction, senescence, epithelial to mesenchymal transition, growth arrest, and pro-inflammatory gene expression) in damaged hepatocytes (dHeps) from CCl4-induced mice with chronic liver injury, resembling a direct chemical reprogramming approach. Systemic administration of 5C in mice with chronic liver injury promoted hepatocyte regeneration, improved liver function, and ameliorated liver fibrosis. The hepatocyte-associated transcriptional networks were reestablished with chemical treatment as revealed by motif analysis of ATAC-seq, and a hepatocyte-enriched transcription factor, Foxa2, was found to be essential for hepatocyte revitalization. Overall, our findings indicate that the phenotype and transcriptional program of dHeps can be reprogrammed to generate functional and regenerative hepatocytes by using only small molecules, as an alternative approach to liver repair and regeneration.

Discrimination of ground-glass nodular lung adenocarcinoma pathological subtypes via transfer learning: A multicenter study.

BACKGROUND: The surgical approach and prognosis for invasive adenocarcinoma (IAC) and minimally invasive adenocarcinoma (MIA) of the lung differ. However, they both manifest as identical ground-glass nodules (GGNs) in computed tomography images, and no effective method exists to discriminate them. METHODS: We developed and validated a three-dimensional (3D) deep transfer learning model to discriminate IAC from MIA based on CT images of GGNs. This model uses a 3D medical image pre-training model (MedicalNet) and a fusion model to build a classification network. Transfer learning was utilized for end-to-end predictive modeling of the cohort data of the first center, and the cohort data of the other two centers were used as independent external validation data. This study included 999 lung GGN images of 921 patients pathologically diagnosed with IAC or MIA at three cohort centers. RESULTS: The predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). The model had high diagnostic efficacy for the training and validation groups (accuracy: 89%, sensitivity: 95%, specificity: 84%, and AUC: 95% in the training group; accuracy: 88%, sensitivity: 84%, specificity: 93%, and AUC: 92% in the internal validation group; accuracy: 83%, sensitivity: 83%, specificity: 83%, and AUC: 89% in one external validation group; accuracy: 78%, sensitivity: 80%, specificity: 77%, and AUC: 82% in the other external validation group). CONCLUSIONS: Our 3D deep transfer learning model provides a noninvasive, low-cost, rapid, and reproducible method for preoperative prediction of IAC and MIA in lung cancer patients with GGNs. It can help clinicians to choose the optimal surgical strategy and improve the prognosis of patients.

3D Printing Technology with Reverse Guide Design in Autogenous Tooth Transplantation: An in vitro Pictorial Report.

The success of autologous tooth transplantation depends on the activity of the periodontal ligament of the donor tooth. Its activity decreases with a longer exposure time. In order to reduce the exposure time of the donor tooth and quickly prepare the alveolar fossa highly matching with the donor tooth root, the clinical data of cone-beam CT (CBCT) was imported into Mimics 21.0 software in this study to obtain three-dimensional (3D) images of the jaw tissue structure. The images were used to extract the target area and select the target tooth. By analysing the information of the recipient region and the donor region, 3-Matic 13.0 software was used to implant the donor virtual into the target region, and restrictive personalised guidance was designed. Subsequently, the surgical guide template was printed by 3D printing technology, and the alveolar fossa was rapidly prepared in vitro. After the operation, the donor tooth was matched with the complete alveolar cavity using 3-Matic13.0 software. The depth deviation of the prepared alveolar cavity was measured within 2.0 mm, and the width deviation was about 1.0 mm. The maximum width deviation is 2.88 mm due to the tilt of the roots. With a high matching degree to the donor tooth root, it needs further and larger clinical studies. Key Words: CBCT, Tooth autotransplantation, 3D printing technology, Computer-aided imaging, Periodontal ligament.

Morphometric evaluation of alveolar bone after orthodontic treatment of multiple impacted teeth in the unilateral maxillary anterior region.

INTRODUCTION: This study aimed to investigate the height and thickness of alveolar bone by cone-beam computed tomography imaging after orthodontic treatment in the unilateral maxillary anterior region and speculate on reasons for the difference in alveolar bone morphology. METHODS: This study selected 11 patients (3 males and 8 females; mean age, 9.42 ± 1.45 years). Cone-beam computed tomography was performed for these 11 patients before and after treatment using Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). Labial and palatal alveolar bone thickness (BT) at root apices and different levels along the roots and loss of alveolar bone height was measured for each impacted tooth and its contralateral homonymous tooth. RESULTS: After orthodontic therapy, all 3 impacted anterior teeth had different degrees of loss of labial alveolar bone height compared with the normal side (central incisor: -1.5 mm, P <0.005; lateral incisor: -1.06 mm, P <0.01; canine: -0.59 mm, P < 0.01). The lateral incisors also showed palatal alveolar bone height loss compared with the unaffected side (-0.8 mm, P <0.005). Alveolar BT at root apices of impacted canines was 1.14 mm thicker than the normal side (P <0.005). Central and lateral incisors were similar to the normal side. The thickness of the alveolar bone at 8, 10, and 12 mm of the impacted canine position was still larger than that on the healthy side, whereas the difference in average thickness between the healthy and affected side had been significantly reduced compared with pretreatment measurements. CONCLUSIONS: There is satisfactory retention of alveolar bone height in canines after orthodontic treatment; however, alveolar bone loss is slightly worse at central and lateral incisors. Retention of alveolar BT was normal for impacted anterior teeth, whereas excess apical alveolar BT at the canines, although still present, was substantially less significant than had been observed before treatment.

PHDs-seq: a large-scale phenotypic screening method for drug discovery through parallel multi-readout quantification.

High-throughput phenotypic screening is a cornerstone of drug development and the main technical approach for stem cell research. However, simultaneous detection of activated core factors responsible for cell fate determination and accurate assessment of directional cell transition are difficult using conventional screening methods that focus on changes in only a few biomarkers. The PHDs-seq (Probe Hybridization based Drug screening by sequencing) platform was developed to evaluate compound function based on their transcriptional effects in a wide range of signature biomarkers. In this proof-of-concept demonstration, several sets of markers related to cell fate determination were profiled in adipocyte reprogramming from dermal fibroblasts. After validating the accuracy, sensitivity and reproducibility of PHDs-seq data in molecular and cellular assays, a panel of 128 signalling-related compounds was screened for the ability to induce reprogramming of keloid fibroblasts (KF) into adipocytes. Notably, the potent ATP-competitive VEGFR/PDGFR inhibitor compound, ABT869, was found to promote the transition from fibroblasts to adipocytes. This study highlights the power and accuracy of the PHDs-seq platform for high-throughput drug screening in stem cell research, and supports its use in basic explorations of the molecular mechanisms underlying disease development.

Isolation and identification of antioxidant constituents from the flowers of Salvia miltiorrhiza.

A new salvianolic acid derivative, (7'E)-(7S, 8S)-salvianolic acid V (1), together with four previously described compounds (2-5) were obtained from the n-butanol fraction of Salvia miltiorrhiza flowers. Their structures were established by a series of spectroscopic methods, and the absolute configuration of 1 was determined by electronic circular dichroism (ECD) calculation. Salvianolic acids (1) and phenolic acids (2-4) showed stronger DPPH free radical scavenging abilities and certain protective effects against H2O2-induced human skin fibroblast (HSF) cells oxidative damage, in which compound 1 (IC50 7.12 µM) possessed more noticeable free radical scavenging activity than the positive control vitamin C (IC50 14.98 µM).

Identification of Differential Compositions of Aqueous Extracts of Cinnamomi Ramulus and Cinnamomi Cortex.

Cinnamomi ramulus (CR) and Cinnamomi cortex (CC), both sourced from Cinnamomum cassia Presl, are commonly used Chinese medicines in the Chinese Pharmacopeia. However, while CR functions to dissipate cold and to resolve external problems of the body, CC functions to warm the internal organs. To clarify the material basis of these different functions and clinical effects, a simple and reliable UPLC-Orbitrap-Exploris-120-MS/MS method combined with multivariate statistical analyses was established in this study with the aim of exploring the difference in chemical compositions of aqueous extracts of CR and CC. As the results indicated, a total of 58 compounds was identified, including nine flavonoids, 23 phenylpropanoids and phenolic acids, two coumarins, four lignans, four terpenoids, 11 organic acids and five other components. Of these compounds, 26 significant differential compounds were identified statistically including six unique components in CR and four unique components in CC. Additionally, a robust HPLC method combined with hierarchical clustering analysis (HCA) was developed to simultaneously determine the concentrations and differentiating capacities of five major active ingredients in CR and CC: coumarin, cinnamyl alcohol, cinnamic acid, 2-methoxycinnamic acid and cinnamaldehyde. The HCA results showed that these five components could be used as markers for successfully distinguishing CR and CC. Finally, molecular docking analyses were conducted to obtain the affinities between each of the abovementioned 26 differential components, focusing on targets involved in diabetes peripheral neuropathy (DPN). The results indicated that the special and high-concentration components in CR showed high docking scores of affinities with targets such as HbA1c and proteins in the AMPK-PGC1-SIRT3 signaling pathway, suggesting that CR has greater potential than CC for treating DPN.

Cucurbitane triterpenes from Hemsleya chinensis tubers and their anti-inflammatory activities.

Six new cucurbitane-type triterpenes, hemchinins A-F (1-6), together with thirteen known ones (7-19) were isolated from ethyl acetate extraction of Hemsleya chinensis tubers. Compounds 1-2 were a group of cucurbitane triterpenes possessing an infrequent pentacyclic framework. Their structures were established by comprehensive UV, IR, HRMS, 1D/2D NMR, and ECD analyses. Bioassay results showed that most isolated compounds exhibited anti-inflammatory actions, in which compounds 13 and 15 exhibited stronger activities at 6.25 µM, with NO inhibition rates of 49.00 ± 0.05% and 48.40 ± 0.10%, respectively.

Natural and Pseudonatural Lindenane Heterodimers from Sarcandra glabra by Molecular Networking.

Sarglaoxolane A (1), the first lindenane-normonoterpene heterodimer fused by tetrahydrofuran, was discovered in Sarcandra glabra guided by the first proposed single-node-based molecular networking approach. Moreover, two pseudonatural derivatives (2 and 3) with an oxa-difuranofurone moiety were transformed from 1 and confirmed by X-ray diffraction, and also proven to exist in the plant extract. A combination of molecular networking and biomimetic transformation can significantly promote the discovery and structural elucidation of novel natural products.

Tumor microenvironment-associated lactate metabolism regulates the prognosis and precise checkpoint immunotherapy outcomes of patients with lung adenocarcinoma.

BACKGROUND: Despite the wide clinical application of checkpoint inhibitor immunotherapy in lung adenocarcinoma, its limited benefit to patients remains puzzling to researchers. One of the mechanisms of immunotherapy resistance may be the dysregulation of lactate metabolism in the immunosuppressive tumor microenvironment (TME), which can inhibit dendritic cell maturation and prevent T-cell invasion into tumors. However, the key genes related to lactate metabolism and their influence on the immunotherapeutic effects in lung adenocarcinoma have not yet been investigated in depth. METHODS: In this study, we first surveyed the dysregulated expression of genes related to lactate metabolism in lung adenocarcinoma and then characterized their biological functions. Using machine learning methods, we constructed a lactate-associated gene signature in The Cancer Genome Atlas cohort and validated its effectiveness in predicting the prognosis and immunotherapy outcomes of patients in the Gene Expression Omnibus cohorts. RESULTS: A 7-gene signature based on the metabolomics related to lactate metabolism was found to be associated with multiple important clinical features of cancer and was an independent prognostic factor. CONCLUSIONS: These results suggest that rather than being simply a metabolic byproduct of glycolysis, lactate in the TME can affect immunotherapy outcomes. Therefore, the mechanism underlying this effect of lactate is worthy of further study.