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Terpenes possess a wide range of structural features and pharmaceutical activities and are promising for drug candidates. With the aim to find bioactive terpene molecules, eight new compounds were isolated from the medicinal plant Nepeta bracteata Benth., including seven new abietane-type diterpenoids (1–7), along with a new ursane-type triterpenoid(8). The structures of compounds 1–8 were elucidated through the detailed spectroscopic analyses of their 1D and 2D NMR and MS data, and the absolute configurations of compounds 1–7 were determined by comparing their experimental and calculated ECD spectra. Compound 1 was a novel degraded carbon diterpene with the disappearing of methyl signal at C-19, while compound 7 possessed a new norabietane-type diterpenoid carbon skeleton with the presence of five-membered lactone arising from ring rearrangement. The anti-inflammatory of all obtained isolates were evaluated on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the results of anti-inflammatory activity screening showed that compared with the LPS model group, all compounds were significantly down-regulation the TNF-α inflammatory factor at the specific concentration, except for compound 6.

Number 2 Feibi Recipe (N2FBR) is a traditional Chinese medicine formula for treating idiopathic pulmonary fibrosis. N2FBR inhibits H2O2-mediated oxidative stress damage in alveolar epithelial cells by increasing autophagy, as we previously demonstrated. However, it is unknown if similar mechanisms occur in vivo. We established a pulmonary fibrosis model by instilling bleomycin (BLM) from the airway to examine the effects of N2FBR on pulmonary fibrosis and investigate its probable mechanism in this work. We discovered that N2FBR treatment effectively alleviated interstitial fibrosis as well as collagen deposition, primarily in upregulating SOD, GSH-Px, T-AOC and downregulating MDA content. N2FBR also increased the expression of LC3B, Beclin-1, LAMP1, TFEB and downregulated the expression of p62, legumain. N2FBR treatment boosted the production of autophagosomes, according to the results of the TEM observation. Furthermore, we explored that N2FBR exerted its anti-oxidative stress and pro-autophagy effects via GSK-3β/mTOR signalling pathway. Therefore, these results provide further evidence for the protective effect of N2FBR in pulmonary fibrosis. Our findings could have ramifications for the development of antifibrosis therapies.

BackgroundAcupuncture has been widely used in the treatment of patients with Parkinson's disease (PD) in the world. Despite we have an in-depth understanding of acupuncture in this field over the past years, there is no available literature on bibliometric analysis on the development of acupuncture on PD. This study was designed to explore the global trend in the research of acupuncture on PD in the recent 20 years by the software CiteSpace (5.8.R3) and VOSviewer (1.6.14).MethodsPublications regarding acupuncture therapy for PD from 2000 to 2021 were retrieved from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to analyze the number of publications, the contribution of countries, institutions, journals, authors, references, and keywords.ResultsA total of 217 studies were extracted from the database. The outputs of the publications in this field showed an upward trend during the past two decades. The country and institutions with the most publications in this field are China, South Korea, and the USA. They were the main contributors to the research. Kyung Hee University and Capital Medical University were the two most productive organizations. Hi-Joon Park had made the greatest contributions to the field. Evidence-based Complementary and Alternative Medicine was the most popular journals in this field. “Electroacupuncture” and “Bee venom acupuncture” were emerging research hotspots.ConclusionThe research on acupuncture on PD is potential. Authors from different countries/regions and organizations need to remove the language and academic barriers to enhance global cooperation and communications. Scholars in this field need to publish their research findings in high-quality journals to gain more attention worldwide. This study indicated that the mechanism leading to the non-motor symptoms of PD, the establishment of appropriate models that fully reflects the non-motor features of human PD, and the efficacy and safety of promising therapies for patients with PD will remain research frontiers in the future.

Polychlorinated biphenyls (PCBs) are widely distributed environmental toxicants, whose biological toxicity is magnified step by step through the transmission of the food chain. However, there is little research about the effect of PCBs on intestinal epithelial barrier function. In this experiment, the effects of PCB exposure on the intestines of zebrafish were evaluated. Animals were exposed to Aroclor 1254 (5 μg/L, 10 μg/L, 15 μg/L). After 21 days, the changes in histology, enzyme biomarkers, intestinal microorganisms, and metabolomics were detected. The inflammation and oxidative stress in the intestines of zebrafish were observed. Additionally, there were significant changes in intestinal microbiota and tissue metabolism, most of which were associated with oxidative stress, inflammation, and lipid metabolism. The results showed that PCBs exposure resulted in intestinal inflammation and oxidative stress in zebrafish.Moreover, intestinal metabolites and intestinal microflora of zebrafish were also disturbed. This study verified that exposure can lead to intestinal damage and changes in intestinal metabolic capacity and microorganisms, enlightening the consequences of PCB exposure.

Background: Ischemic stroke is the most common stroke incident. Sphingosine-1-phosphate (S1P) receptor 3 (S1PR3) is a member of the downstream G protein-coupled receptor family of S1P. The effect of S1PR3 on ischemic stroke remains elusive.Methods: We downloaded two middle cerebral artery occlusion (MCAO) microarray datasets from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs). Then, we performed a weighted gene coexpression network analysis (WGCNA) and identified the core module genes related to ischemic stroke. We constructed a protein–protein interaction (PPI) network for the core genes in which DEGs and WGCNA intersected. Finally, we discovered that S1PR3 was involved as the main member of the red proteome. Then, we explored the mechanism of S1PR3 in the mouse tMCAO model. The S1PR3-specific inhibitor CAY10444 was injected into the abdominal cavity of mice after cerebral ischemia/reperfusion (I/R) injury, and changes in the expression of blood–brain barrier-related molecules were measured using PCR, western blotting, and immunofluorescence staining.Results: Both GEO datasets showed that S1PR3 was upregulated during cerebral I/R in mice. WGCNA revealed that the light yellow module had the strongest correlation with the occurrence of IS. We determined the overlap with DEGs, identified 146 core genes that are potentially related to IS, and constructed a PPI network. Finally, S1PR3 was found to be the main member of the red proteome. In the mouse cerebral I/R model, S1PR3 expression increased 24 h after ischemia. After the administration of CAY10444, brain edema and neurological deficits in mice were ameliorated. CAY10444 rescued the decreased expression of the tight junction (TJ) proteins zonula occludens 1 (ZO1) and occludin after ischemia induced by transient MCAO (tMCAO) and reduced the increase in aquaporin 4 (AQP4) levels after tMCAO, preserving the integrity of the BBB. Finally, we found that S1PR3 is involved in regulating the mitogen-activated protein kinase (MAPK) and (phosphatidylinositol-3 kinase/serine-threonine kinase) PI3K-Akt signaling pathways.Conclusion: S1PR3 participates in the regulation of blood–brain barrier damage after cerebral I/R. S1PR3 is expected to be an indicator and predictor of cerebral ischemia, and drugs targeting S1PR3 may also provide new ideas for clinical medications.

Background. The objective of this study is to determine optic nerve head vascular changes in patients with obstructive sleep apnea‐hypopnea syndrome (OSAS) by utilizing an optical coherence tomography angiography (OCTA) device. Methods. A detailed studies search was screened in the PubMed, Embase, the Cochrane Library, and Web of Science databases from inception to August 2023. We reviewed and examined optic nerve head vascular density in eyes with OSAS and controls. The mean difference and 95% confidence interval were calculated to evaluate continuous outcomes. Review Manager version 5.4.1 was applied for analysing pooled data. Results. Six eligible studies were included in our meta‐analysis. The radial peripapillary capillary (RPC) whole enface vessel density (VD) measured by OCTA in the mild‐to‐moderate and severe OSAS groups was significantly lower compared to the controls (MD = −0.96, P = 0.03; MD = −1.42, P = 0.001, respectively). For RPC peripapillary VD, eyes in mild‐to‐moderate OSAS showed a trending decrease compared to the controls (MD = −1.71, P = 0.05), and there was a remarkable difference between eyes with severe OSAS and the controls (MD = −3.08, P = 0.004). In addition, the RPC inside disc VD was decreased in severe OSAS eyes than in the controls (MD = −0.07, P = 0.94). Conclusions. Our results revealed that peripapillary vascular density was attenuated in patients with OSAS. Moreover, on the basis of these findings, we suggest that optic nerve head vascular density measured by OCTA may be used as a potential tool to diagnose and monitor the severity of patients with OSAS. [ABSTRACT FROM AUTHOR]

The Xujiashan Sb deposit located at the Mufushan fold thrust belt of the Yangtze block is one of the most important Sb deposits in this district. Stibnite in this deposit contains high and various contents of Se, but research on the distribution and enrichment of Se in stibnite remains limited. This paper conducts geochemical composition, C-H-O isotopic composition, and scanning electron microscopy morphology of the Xujiashan deposit to discuss the sources of ore-forming materials and fluid, as well as the distribution and enrichment mechanisms of selenium in stibnite. The results showed that the ores have trace element compositions comparable with the wall rocks, and Sb and Se contents are significantly higher than the average carbonate rocks. The δ13CPDB values of calcite and quartz range from −12.8‰ to 5.5‰, the δ18OSMOW values range from 20.4‰ to 24‰, and the δDV-SMOW values range from −57.8‰ to −86.9‰. Trace element and isotope compositions indicate that the ore-forming materials were mainly derived from the wall rocks (sedimentary–metamorphic rocks) that S, Se, and Sb dissolved during fluid–rock interactions. The ore-forming fluids were metamorphic water produced by metamorphism, which had experienced multistage mixing with meteoric water and organic-rich fluids. Selenium substitutes for sulfur in the stibnite crystal lattice, causing rhythmically distributed Se contents in stibnite, which resulted from multistage physicochemical changes in ore-forming fluids during crystallization. The varied patterns of Se contents are the result of different cross-sections of the stibnite. [ABSTRACT FROM AUTHOR]

Genomic evidence suggests that lysogenic viruses significantly influence the evolution of their host communities and soil microbial ecology and functionality. However, the response of soil viral reproductive strategies (VRS) to environmental factors, in particular soil water stress, remains poorly understood. We investigated this by employing a laboratory microcosm incubation system with different soil moisture levels (30%, 60% and 90% field capacity). Our study focused on soil biochemical properties, bacterial and viral populations, lysogenic fractions and virus/bacteria ratio (VBR). The results showed that soil moisture significantly affected bacterial and viral counts, lysogenic fractions and VBR (p < 0.01), with bacterial counts increasing and viral counts decreasing with increasing soil moisture. The lysogenic fraction peaked at low moisture, suggesting a shift in viral strategy under hydration stress, which may affect virus‐bacteria interactions and nutrient dynamics, enhancing host adaptability. Analyses using correlation, random forest and structural equation modelling identified soil moisture as the dominant factor shaping VRS by altering nutrient availability and host population. These findings provide a new insight into microbial regulation of feedback to environmental change from the life history strategies of soil viruses. [ABSTRACT FROM AUTHOR]

Histology slide, tissue microbes, and the host gene expression can be independent prognostic factors of colorectal cancer (CRC), but the underlying associations and biological significance of these multimodal omics remain unknown. Here, we comprehensively profiled the matched pathological images, intratumoral microbes, and host gene expression characteristics in 527 patients with CRC. By clustering these patients based on histology slide features, we classified the patients into two histology slide subtypes (HSS). Onco‐microbial community and tumor immune microenvironment (TIME) were also significantly different between the two subtypes (HSS1 and HSS2) of patients. Furthermore, variation in intratumoral microbes–host interaction was associated with the prognostic heterogeneity between HSS1 and HSS2. This study proposes a new CRC classification based on pathological image features and elucidates the process by which tumor microbes–host interactions are reflected in pathological images through the TIME. [ABSTRACT FROM AUTHOR]

Accurate measurement of endogenous steroid hormones in serum is a powerful tool for understanding the status of human adrenal diseases. Isotope dilution–liquid chromatography–tandem mass spectrometry is the most commonly used method for determination of steroids in serum. In this study, we used a laboratory-constructed quadrupole-linear ion trap (Q-LIT) tandem mass spectrometer to develop a new method for the quantification of five steroid hormones in serum. A simple and efficient pretreatment was improved, wherein the serum was extracted once by a mixed solvent of 1.0 mL of ethyl acetate and n-hexane. Using the optimized method, the regression coefficients of the calibration curves were all higher than 0.99, the limits of detection were from 0.31 to 1.25 ng mL−1, and the limits of quantification were between 1.00 and 2.50 ng mL−1. The intra-day (n = 3) relative standard deviations ranged from 4.24% to 13.79%, and the inter-day (n = 3) relative standard deviations from 3.99% to 11.43%. After internal standard correction, the relative recoveries of all steroids were from 86.08% to 106.60%. Twenty-two serum samples were analyzed by Q-LIT, which was compared with commercial triple quadrupole mass spectrometer. The results of the instruments had high consistency. Therefore, Q-LIT accurately quantified steroid hormones in human samples and may be used for clinical diagnosis and monitoring of hormone-dependent diseases. [ABSTRACT FROM AUTHOR]

LC3 lipidation plays an important role in the regulation of macroautophagy and LC3-associated microautophagy. The E1-like enzyme ATG7 is one of the core components that are directly involved in LC3 lipidation reaction. Here, we provide evidence showing that acetylation of ATG7 tightly controls its enzyme activity to regulate the induction of macroautophagy and LC3-associated microautophagy. Mechanistically, acetylation of ATG7 disrupts its interaction with the E2-like enzyme ATG3, leading to an inhibition of LC3 lipidation in vitro and in vivo. Functionally, in response to various different stimuli, cellular ATG7 undergoes deacetylation to induce macroautophagy and LC3-associated microautophagy, which are necessary for cells to eliminate cytoplasmic DNA and degrade lysosome membrane proteins, respectively. Taken together, these findings reveal that ATG7 acetylation acts as a critical rheostat in controlling LC3 lipidation and related cellular processes. Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy-related; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; CREBBP/CBP: CREB binding protein; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EP300/p300: E1A binding protein p300; IFNB1: interferon beta 1; ISD: interferon stimulatory DNA; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MEF: mouse embryonic fibroblast; MTOR: mechanistic target of rapamycin kinase; NAM: nicotinamide; PE: phosphatidylethanolamine; PTM: post-translational modification; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SIRT: sirtuin; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TSA: trichostatin A; ULK1: unc-51 like autophagy activating kinase 1; WIPI2: WD repeat domain, phosphoinositide interacting 2; WT: wild-type. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS)-mediated alveolar epithelial cell (AEC) injury and apoptosis are considered to be the initiating link of idiopathic pulmonary fibrosis (IPF), and protecting AECs can alleviate IPF. This study aimed to explore the protective effect of number 2 Feibi recipe (FBR-2) medicated serum on H2O2-mediated oxidative stress injury in AECs and further explore its mechanism. We found that FBR-2 can regulate downstream antioxidant enzymes expression by activating nuclear factor erythroid 2-related factor 2 (Nrf2), reducing the level of intracellular ROS, protecting mitochondrial function and improving cell survival. FBR-2 can also activate mitophagy through the PINK1/Parkin pathway. Moreover, FBR-2 can inhibit apoptosis by blocking the mitochondrial apoptosis mechanism. In summary, these data indicate that FBR-2 medicated serum can inhibit H2O2-mediated oxidative stress damage in AECs by regulating the balance of mitophagy/apoptosis. This study provides new evidence for the antifibrotic effect of FBR-2 and provides new drug candidates for the clinical treatment of IPF.

BackgroundIschemic stroke (IS) is a common disease endangering human life and health. Cerebral ischemia triggers a series of complex harmful events, including excitotoxicity, inflammation and cell death, as well as increased nitric oxide production through the activation of nitric oxide synthase (NOS). Oxidative stress plays a major role in cerebral ischemia and reperfusion. Sphingosine 1-phosphate receptor subtype 3 (S1PR3), a member of S1P’s G protein-coupled receptors S1PR1-S1PR5, is involved in a variety of biological effects in the body, and its role in regulating oxidative stress during cerebral ischemia and reperfusion is still unclear.MethodsTransient middle cerebral artery occlusion (tMCAO) mice were selected as the brain ischemia–reperfusion (I/R) injury model. Male C57/BL6 mice were treated with or without a selective S1PR3 inhibition after tMCAO, and changes in infarct volume, Nissl staining, hematoxylin-eosin (H&E) staining and NOS protein, nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) content after tMCAO were observed.ResultsIn the cerebral ischemia–reperfusion model, inhibition of S1PR3 improved the infarct volume and neuronal damage in mice after tMCAO. Similarly, inhibition of S1PR3 can reduce the expression of NO synthase subtype neuronal NOS (nNOS) and reduce the production of NO after cerebral ischemia. After cerebral ischemia and reperfusion, the oxidative stress response was enhanced, and after the administration of the S1PR3 inhibitor, the SOD content increased and the MDA content decreased, indicating that S1PR3 plays an important role in regulating oxidative stress response.ConclusionInhibiting S1PR3 attenuates brain damage during I/R injury by regulating nNOS/NO and oxidative stress, which provides a potential new therapeutic target and mechanism for the clinical treatment of IS.

Abstract Ellagic acid (EA) has been reported to have antiproliferative and antioxidant properties, but its function in esophageal squamous cell carcinoma (ESCC) has not been investigated yet. In the current study, EA was found have a significant anti‐tumor activity in ESCC. In specific, EA inhibited ESCC cell survival in both of a concentration‐ and time‐dependent manner. And our results showed that EA promoted ESCC cell apoptosis, including inducing the cleavages of PARP, and inhibiting the expression of anti‐apoptotic proteins. In mechanistic, EA markedly suppressed STAT3‐driven luciferase activity, and inhibited both of the endogenous and cytokines‐induced STAT3 activation in ESCC cells. Further investigations indicated that EA could significantly upregulate SHP‐1 expression, a negative modulator of STAT3 signaling. In contrast, knockdown of SHP‐1 could attenuate the effects of EA on inhibiting ESCC cell survival. Moreover, we found that EA could inhibit RNF6 expression, an E3 of SHP‐1, and overexpressing RNF6 could also significantly attenuate the effects of EA on inhibiting ESCC cell survival, which further revealed that EA could inhibit STAT3 signaling by modulating RNF6/SHP‐1 axis. Our present study indicated that EA could be as a novel STAT3 inhibitor for the treatment of ESCC.

Objective: We performed this study to investigate whether the EDNRA gene rs1878406 C > T polymorphism is associated with risk of large artery atherosclerosis (LAA) stroke in the Chinese Han population.Methods: Genotyping of rs1878406 was performed in 1,112 LAA stroke patients and 1,192 healthy controls. Multivariate logistic regression analyses were applied to assess the effect of the rs1878406 C > T polymorphism on susceptibility to LAA stroke.Results: A significant increase of LAA stroke risk was found in the recessive model (TT vs. CC/TC, OR = 1.74, 95% CI = 1.23–2.48, p = 0.002) and co-dominant model (TC vs. CC, OR = 1.06, 95% CI = 0.89–1.27, TT vs. CC, OR = 1.79, 95% CI = 1.25–2.55, p = 0.006). However, the interaction between age and genotypes of rs1878406 was not statistically significant, and no significant interactive effect was observed between the rs1878406 C > T polymorphism and sex (p > 0.05).Conclusion: The rs1878406 C > T polymorphism is associated with increased risk of LAA stroke in the Chinese Han population.

Background Chinese herbs for supplementing qi and activating blood circulation (CH) combined with N-acetylcysteine (NAC) is widely used for idiopathic pulmonary fibrosis (IPF) in China, but there is a lack of literature to evaluate its efficacy and clinical value. Purpose This study compared CH + NAC with other treatments by network meta-analysis to clarify its clinical value. Methods Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP Database, and China Biology Medicine were searched. Outcomes included lung function (DLCO (%), VC (%), FVC (%), FVC (L)), 6-min walking distance (6MWD), score of St George’s respiratory questionnaire (SGRQ), blood gas analysis (PaO2, PaCO2). The data were analyzed by Review Manager 5.4, Stata 12.0 and ADDIS 1.16.5. Results 23 studies including 1390 patients (702 in intervention group and 688 in control group) were collected to compare 8 outcome indicators among different treatments involving CH, CH+NAC, CH+PFD, NAC, PFD and PFD+NAC on IPF. Network meta-analysis showed that CH was better than NAC in terms of DLCO (%) (MD = 5.14, 95%CI: 1.01 to 8.68) and 6MWD (MD = 49.17, 95%CI: 25.97 to 71.36) as well as PFD + NAC was better than NAC in terms of FVC (L) (MD = -0.56, 95%CI: -0.83 to -0.31). In rankings results, CH + NAC is the best in terms of FVC (%), SGRQ, PaO2 and PaCO2; CH is the best in terms of DLCO (%), VC (%) and 6MWD; CH + PFD is the best in terms of FVC (L). Conclusion CH related treatments may have advantages in the treatment of IPF and CH + NAC may have clinical application value. However, limited by the quality and quantity of researches included, more rational and scientific randomized controlled trials containing large sample sizes need to be conducted to further verify our conclusions.