Long-Term Risk of Reintervention After Surgical Leiomyoma Treatment in an Integrated Health Care System.

OBJECTIVE: To compare long-term risk of reintervention across four uterus-preserving surgical treatments for leiomyomas and to assess effect modification by sociodemographic factors in a prospective cohort study in an integrated health care delivery system. METHODS: We studied a cohort of 10,324 patients aged 18-50 (19.9% Asian, 21.2% Black, 21.3% Hispanic, 32.5% White, 5.2% additional races and ethnicities) who had a first uterus-preserving procedure (abdominal, laparoscopic, or vaginal myomectomy [referred to as myomectomy]; hysteroscopic myomectomy; endometrial ablation; uterine artery embolization) after leiomyoma diagnosis in the 2009-2021 electronic health records of Kaiser Permanente Northern California. We followed up patients until reintervention (second uterus-preserving procedure or hysterectomy) or censoring. We used a Kaplan-Meier estimator to calculate the cumulative incidence of reintervention and Cox regression models to estimate hazard ratios and 95% CIs comparing rates of reintervention across procedures, adjusting for age, parity, race and ethnicity, body mass index (BMI), Neighborhood Deprivation Index, and year. We also assessed effect modification by demographic characteristics. RESULTS: Median follow-up was 3.8 years (interquartile range 1.8-7.4 years). Index procedures were 18.0% (1,857) hysteroscopic myomectomies, 16.2% (1,669) uterine artery embolizations, 21.4% (2,211) endometrial ablations, and 44.4% (4,587) myomectomies. Accounting for censoring, the 7-year reintervention risk was 20.6% for myomectomy, 26.0% for uterine artery embolization, 35.5% for endometrial ablation, and 37.0% for hysteroscopic myomectomy; 63.2% of reinterventions were hysterectomies. Within each procedure type, reintervention rates did not vary by BMI, race and ethnicity, or Neighborhood Deprivation Index. However, rates of reintervention after uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy decreased with age, and reintervention rates for hysteroscopic myomectomy were higher for parous than nulliparous patients. CONCLUSION: Long-term reintervention risks for uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy are greater than for myomectomy, with potential variation by patient age and parity but not BMI, race and ethnicity, or Neighborhood Deprivation Index.

[Changes in Soil Nitrogen Components and Their Relationship with Environmental Factors with Different Tea Plantation Ages].

Changes in soil nitrogen components in tea gardens affect the soil nitrogen supply capacity and nitrogen cycle. In this study, soil samples were collected from forest land, cultivated land, and tea gardens with different plantation ages (30, 50, and 70 years) to explore the changes in soil nitrogen components and their relationship with physicochemical properties and enzyme activities. The results showed that:① with the increase in tea plantation age, the silt, total phosphorus, and urease and catalase activities gradually increased, whereas the sand, clay, pH, electrical conductivity, soil organic carbon, and the activities of invertase gradually decreased. The alkaline phosphatase activity increased first and then decreased with the increase in tea plantation age, and no significant differences were observed in soil water content and acid phosphatase activity. ② With the increase in tea plantation age, the contents of acid ammonia nitrogen, amino acid nitrogen, and nitrate nitrogen (NO3--N) increased significantly, and the contents of total nitrogen, acid ammonia nitrogen, hydrolyzable unknown nitrogen, and non-hydrolyzable nitrogen in tea gardens were significantly higher than those in forest land. ③ The total phosphorus, alkaline phosphatase, and urease were the main factors affecting soil nitrogen components. Among them, organic nitrogen components were significantly correlated with total phosphorus and alkaline phosphatase, and inorganic nitrogen components were significantly correlated with alkaline phosphatase, whereas total nitrogen had significant correlations with sand, silt, total phosphorus, urease, and alkaline phosphatase.

Shenfu injection: a review of pharmacological effects on cardiovascular diseases.

Shenfu injection (SFI), composed of ginseng and aconite, is a Chinese patent developed from the classic traditional prescription Shenfu Decoction created more than 700 years ago. SFI has been widely used in China for over 30 years for treating cardiovascular diseases. The main components in it include ginsenosides and aconitum alkaloids. In recent years, the role of SFI in the treatment of cardiovascular diseases has attracted much attention. The pharmacological effects and therapeutic applications of SFI in cardiovascular diseases are summarized here, highlighting pharmacological features and potential mechanisms developments, confirming that SFI can play a role in multiple ways and is a promising drug for treating cardiovascular diseases.

Transcriptional regulation analysis reveals the complexity of metamorphosis in the Pacific oyster (Crassostrea gigas).

Many marine invertebrate phyla are characterized by indirect development. These animals transit from planktonic larvae to benthic spats via settlement and metamorphosis, which contributes to their adaption to the marine environment. Studying the biological process of metamorphosis is, thus, key to understanding the origin and evolution of indirect development. Although numerous studies have been conducted on the relationship between metamorphosis and the marine environment, microorganisms, and neurohormones, little is known about gene regulation network (GRN) dynamics during metamorphosis. Metamorphosis-competent pediveligers of the Pacific oyster Crassostrea gigas were assayed in this study. By assaying gene expression patterns and open chromatin region changes of different samples of larvae and spats, the dynamics of molecular regulation during metamorphosis were examined. The results indicated significantly different gene regulation networks before, during and post-metamorphosis. Genes encoding membrane-integrated receptors and those related to the remodeling of the nervous system were upregulated before the initiation of metamorphosis. Massive biogenesis, e.g., of various enzymes and structural proteins, occurred during metamorphosis as inferred from the comprehensive upregulation of the protein synthesis system post epinephrine stimulation. Hierarchical downstream gene networks were then stimulated. Some transcription factors, including homeobox, basic helix-loop-helix and nuclear receptors, showed different temporal response patterns, suggesting a complex GRN during the transition stage. Nuclear receptors, as well as their retinoid X receptor partner, may participate in the GRN controlling oyster metamorphosis, indicating an ancient role of the nuclear receptor regulation system in animal metamorphosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00204-y.

Intravenous high-dose vitamin C monotherapy for sepsis and septic shock: A meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness of intravenous high-dose vitamin C in sepsis and septic shock patients by meta-analysis. METHODS: The PubMed, Embase, and Cochrane Library electronic databases were searched to identify relevant studies. The primary outcome was defined as the short-term all-cause mortality rate. Secondary outcomes included duration of vasoactive drug use, intensive care unit length of stay, sequential organ failure assessment scores up to 96 hours after treatment and 90-day mortality. Review Manager version 5.4 was used to perform the meta-analysis. Relative risk and mean differences (MD) with 95% confidence intervals were determined using fixed- or random-effects models. RESULTS: Eight randomized controlled trials (RCTs) comprising 1394 patients were eligible for assessment. Overall, the pooled results showed that high-dose vitamin C decreased short-term all-cause mortality in patients with sepsis, but no significant differences were observed in patients with septic shock. Additionally, high-dose vitamin C was associated with decreased duration of vasoactive drug use in patients with sepsis, but not in patients with septic shock. However, it did not significantly affect the duration of intensive care unit stay in RCTs of patients with sepsis and septic shock. Additionally, it did not significantly affect sequential organ failure assessment scores 96 hours post-treatment or 90-day mortality. CONCLUSION: These results suggest that intravenous high-dose vitamin C may improve outcomes in patients with sepsis, but do not benefit patients with septic shock. Further RCTs and other studies should be conducted to determine whether vitamin C should be recommended as an adjunctive sepsis treatment.

[Effects of Supplementation of Different Amendments on Soil Heavy Metals and Enzyme Activities in Coastal Saline Land].

The supplementation of soil amendments may not only improve the soil physical and chemical properties but also lead to the accumulation of heavy metals in soil. This experiment included six treatments:control (CK), organic manure (OM), polyacrylamide+organic manure (PAM+OM), straw mulching+organic manure (SM+OM), buried straw+organic manure (BS+OM), and bio-organic manure+organic manure (BM+OM) to explore the effects of different soil amendments on heavy metals and soil enzyme activities in coastal saline land and the relationship between them. The results revealed that compared with that in the CK treatment, the contents of soil Cr, Cu, Ni, and Pb exhibited an upward trend after the supplementation of soil amendments, among which the SM+OM and PAM+OM treatments had the most significant effects on the contents of soil Cr and Cu, respectively, whereas the BM+OM treatment had the most significant effects on the contents of soil Ni and Pb. Compared with those in the CK treatment, the activities of soil invertase and urease increased significantly following supplementation of soil amendments, and the BM+OM treatment had the best effect. The alkaline phosphatase activity exhibited a slightly upward trend after the supplementation of soil amendments, whereas the catalase activity did not change significantly. The redundancy analysis revealed that the first two axes cumulatively accounted for 70.3% of the variability in enzyme activities, and the importance of single soil heavy metals on soil enzyme activity was as follows:Ni>Cu>Cr>Pb.

Spatiotemporal evolution of dissolved organic matter (DOM) and its response to environmental factors and human activities.

The South-to-North Water Diversion East Project (SNWDP-E) is an effective way to realize the optimal allocation of water resources in China. The North Dasha River (NDR) is the reverse recharge section that receives water from the Yufu River to the Wohushan Reservoir transfer project line in the SNWDP. However, the dissolved organic matter (DOM) evolution mechanism of seasonal water transfer projects on tributary waters has not been fully elucidated. In this paper, the NDR is the main object, and the changes in the composition and distribution of spectral characteristics during the winter water transfer period (WT) as well as during the summer non-water transfer period (NWT) are investigated by parallel factor analysis (PARAFAC). The results showed that the water connectivity caused by water transfer reduces the environmental heterogeneity of waters in the basin, as evidenced by the ammonia nitrogen (NH4+-N) and total phosphorus (TP) in the water body were significantly lower (p<0.05, p<0.01) during the water transfer period than the non-water transfer period. In addition, the fluorescence intensity of DOM was significantly lower in the WT than the NWT (p<0.05) and was mainly composed of humic substances generated from endogenous sources with high stability. While the NWT was disturbed by anthropogenic activities leading to significant differences in DOM composition in different functional areas. Based on the redundancy analysis (RDA) and multiple regression analysis, it was found that the evolution of the protein-like components is dominated by chemical oxygen demand (COD) and NH4+-N factors during the WT. While the NWT is mainly dominated by total nitrogen (TN) and TP factors for the evolution of the humic-like components. This study helps to elucidate the impact of water transfer projects on the trunk basin and contribute to the regulation and management of inter-basin water transfer projects.

Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway.

Background: The Ze-Qi decoction (ZQD) is a traditional Chinese herbal formula commonly applied to treat lung cancer in China. This study aimed to assess the effective ingredients and molecular mechanisms of ZQD in treating non-small cell lung cancer (NSCLC) based on network pharmacology combined with experimental validation. Methods: Network pharmacology, bioinformatics, and molecular docking analyses were conducted to explore the mechanism of ZQD for treating NSCLC, which was further confirmed by animal experiments. Results: In total, 117 bioactive ingredients and 499 target proteins of ZQD were identified. Network pharmacology revealed 7 core active ingredients and 74 core target proteins. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the PI3K/Akt and p53 signaling pathways may be crucial in NSCLC treatment. Molecular docking analysis revealed that the seven crucial bioactive ingredients complexed with PI3K, Akt, and p53. The animal experiment results validated that ZQD treatment promoted cell apoptosis and cell cycle arrest, thereby inhibiting NSCLC growth and metastasis. Furthermore, ZQD treatment caused a significant increase in p53 and Bax, while leading to a distinct reduction in p-PI3K (Tyr317), p-Akt (Ser473), VEGFA, CD31, MMP2, MMP9, Bcl2, and CDK2. Conclusions: ZQD inhibited the growth and metastasis of NSCLC subcutaneous tumors in C57BL/6J mice via the PI3K/Akt/p53 signaling pathway.

Age-related hearing loss and its potential drug candidates: a systematic review.

BACKGROUND: Age-related hearing loss (ARHL) is one of the main illnesses afflicting the aged population and has a significant negative impact on society, economy, and health. However, there is presently no appropriate therapeutic treatment of ARHL due to the absence of comprehensive trials. OBJECTIVES: The goal of this review is to systematically evaluate and analyze recent statistics on the pathologic classifications, risk factors, treatment strategies, and drug candidates of ARHL, including that from traditional Chinese medicine (TCM), to provide potential new approaches for preventing and treating ARHL. METHODS: Literature related to ARHL was conducted in databases such as PubMed, WOS, China National Knowledge Infrastructure (CNKI), and Wanfang from the establishment of the database to Jan, 2023. The pathology, causal factor, pathophysiological mechanism, treatment strategy, and the drug candidate of ARHL were extracted and pooled for synthesis. RESULTS: Many hypotheses about the etiology of ARHL are based on genetic and environmental elements. Most of the current research on the pathology of ARHL focuses on oxidative damage, mitochondrial dysfunction, inflammation, cochlear blood flow, ion homeostasis, etc. In TCM, herbs belonging to the kidney, lung, and liver meridians exhibit good hearing protection. Seven herbs belonging to the kidney meridian, 9 belonging to the lung meridian, and 4 belonging to the liver meridian were ultimately retrieved in this review, such as Polygonum multiflorum Thunb., Panax ginseng C.A. Mey, and Pueraria lobata (Willd.) Ohwi. Their active compounds, 2,3,4',5-Tetrahydroxystilbene-2-O-D-glucoside, ginsenoside Rb1, and puerarin, may act as the molecular substance for their anti-ARHL efficacy, and show anti-oxidative, neuroprotective, anti-inflammatory, anti-apoptotic, or mitochondrial protective effects. CONCLUSION: Anti-oxidants, modulators of mitochondrial function, anti-inflammation agents, vasodilators, K+ channel openers, Ca2+ channel blockers, JNK inhibitors, and nerve growth factors/neurotrophic factors all contribute to hearing protection, and herbs are an important source of potential anti-ARHL drugs.

Effects of Gestational Arsenic Exposures on Placental and Fetal Development in Mice: The Role of Cyr61 m6A.

BACKGROUND: Several epidemiological investigations demonstrated that maternal arsenic (As) exposure elevated risk of fetal growth restriction (FGR), but the mechanism remains unclear. OBJECTIVES: This study aimed to investigate the effects of gestational As exposure on placental and fetal development and its underlying mechanism. METHODS: Dams were exposed to 0.15, 1.5, and 15mg/L NaAsO2 throughout pregnancy via drinking water. Sizes of fetuses and placentas, placental histopathology, and glycogen content were measured. Placental RNA sequencing was conducted. Human trophoblasts were exposed to NaAsO2 (2µM) to establish an in vitro model of As exposure. The mRNA stability and protein level of genes identified through RNA sequencing were measured. N6-Methyladenosine (m6A) modification was detected by methylated RNA immunoprecipitation-quantitative real-time polymerase chain reason (qPCR). The binding ability of insulin-like growth factor 2 binding protein 2 to the gene of interest was detected by RNA-binding protein immunoprecipitation-qPCR. Intracellular S-adenosylmethionine (SAM) and methyltransferase activity were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and colorimetry, respectively. In vitro As+3 methyltransferase (As3MT) knockdown or SAM supplementation and in vivo folic acid (FA) supplementation were used to evaluate the protective effect. A case-control study verified the findings. RESULTS: Sizes of fetuses (exposed to 1.5 and 15mg/L NaAsO2) and placentas (exposed to 15mg/L NaAsO2) were lower in As-exposed mice. More glycogen+ trophoblasts accumulated and the expression of markers of interstitial invasion was lower in the 15mg/L NaAsO2-exposed mouse group in comparison with control. Placental RNA sequencing identified cysteine-rich angiogenic inducer 61 (Cyr61) as a candidate gene of interest. Mechanistically, mice and cells exposed to As had lower protein expression of CYR61, and this was attributed to a lower incidence of Cyr61 m6A. Furthermore, cells exposed to As had lower methyltransferase activity, suggesting that this could be the mechanism by which Cyr61 m6A was affected. Depletion of intracellular SAM, a cofactor for m6A methyltransferase catalytic domain, partially contributed to As-induced methyltransferase activity reduction. Either As3MT knockdown or SAM supplementation attenuated As-induced Cyr61 m6A down-regulation. In mice, FA supplementation rescued As-induced defective trophoblastic invasion and FGR. In humans, a negative correlation between maternal urinary As and plasma CYR61 was observed in infants who were small for gestational age. DISCUSSION: Using in vitro and in vivo models, we found that intracellular SAM depletion-mediated Cyr61 m6A down-regulation partially contributed to As-induced defective trophoblastic invasion and FGR. https://doi.org/10.1289/EHP12207.

A Versatile PDA(DOX) Nanoplatform for Chemo-Photothermal Synergistic Therapy against Breast Cancer and Attenuated Doxorubicin-Induced Cardiotoxicity.

Photothermal therapy (PTT) is a highly clinical application promising cancer treatment strategy with safe, convenient surgical procedures and excellent therapeutic efficacy on superficial tumors. However, a single PTT is difficult to eliminate tumor cells completely, and tumor recurrence and metastasis are prone to occur in the later stage. Chemo-photothermal synergistic therapy can conquer the shortcomings by further killing residual tumor cells after PTT through systemic chemotherapy. Nevertheless, chemotherapy drugs' extreme toxicity is also a problematic issue to be solved, such as anthracycline-induced cardiotoxicity. Herein, we selected polydopamine nanoparticles (PDA) as the carrier of the chemotherapeutic drug doxorubicin (DOX) to construct a versatile PDA(DOX) nanoplatform for chemo-photothermal synergistic therapy against breast cancer and simultaneously attenuated DOX-induced cardiotoxicity (DIC). The excellent photothermal properties of PDA were used to achieve the thermal ablation of tumors. DOX carried out chemotherapy to kill residual and occult distant tumors. Furthermore, the PDA(DOX) nanoparticles significantly alleviate DIC, which benefits from PDA's excellent antioxidant enzyme activity. The experimental data of the chemotherapy groups showed that the results of the PDA(DOX) group were much better than the DOX group. This study not only effectively inhibits cancer but tactfully attenuates DIC, bringing a new perspective into synergistic therapy against breast cancer.

Ethanolic extract of Pereskia aculeata induces Anti-Inflammatory Responses through P38/MK2/TTP-mediated signaling pathway.

Pereskia aculeata Miller, a member of the Cactaceae family, is a plant with pharmacological potential due to its containing compounds with various biological activities, which include anti-inflammatory, anti-cancer and analgesic activities. In this study, we evaluated the anti-inflammatory effects of an ethanolic extract of P. aculeata Miller (EEPA) and the signalling pathways by which it exerts these effects. In vitro, EEPA inhibited the secretion of inflammatory factors NO, IL-6 and PGE2 in ipopolysaccharide-stimulated RAW264.7 macrophages (P<0.05). Treatment of RAW264.7 cells with EEPA also significantly decreased the levels of P-P38 and P-MK2, while upregulating the expression of TTP (P<0.05). In vivo anti-inflammatory activity assays revealed that EEPA reduced the degree of foot and joint swelling, the splenic index and the serum concentrations of TNF-α and IL-6 in in adjuvant-induced arthritis rats (P<0.05). Similarly, EEPA treatment of mice inhibited the acetic acid-induced exudation of Evans blue dye from peritoneal capillaries and significantly prolonged heat-stimulated pain response time (P<0.05). Taken together, these results suggest that EEPA exerts anti-inflammatory effects in vitro and in vivo. Thus, this study provides experimental and technical support for the development of a novel anti-inflammatory treatment based on P. aculeata Miller.

Tongue acupuncture for the treatment of post-stroke dysphagia: a meta-analysis of randomized controlled trials.

Objectives: Post-stroke dysphagia is the most common neurological impairment after stroke. The swallowing process is controlled by a network made up of the cerebral cortex, subcortical area, and brainstem structure. The disruption of the swallowing network after stroke leads to dysphagia. The affected swallowing muscles after stroke mainly include the laryngeal muscles (suprahyoid muscle and thyrohyoid muscle) and infrahyoid muscle. These muscles experience kinematic effects and muscle strength weakens, resulting in reduced movement in the swallowing process. Acupuncture can change the excitability of cerebral cortical nerve cells, promote the recovery of neurological function, and enhance neuromuscular excitability, ultimately improving the control of swallowing-related nerves and muscles and promoting swallowing functional recovery. In this meta-analysis, we systematically evaluate the clinical efficacy of acupuncture in the treatment of post-stroke dysphagia. Methods: Randomized controlled trials of tongue acupuncture therapy for post-stroke dysphagia were searched and selected from seven electronic databases (PubMed, CBM, Cochrane, Embase, CNKI, VPCS, and Wan fang). The Cochrane Collaboration tool was used to conduct methodological quality assessment. Rev. Man 5.4 software was utilized to perform data analysis. Results: A total of 15 studies with 1,094 patients were included. Meta-analysis Showed that WST score WST score (MD = -0.56, 95% CI (-1.23, 0.12), Z = 1.62, p < 0.00001), SSA score (MD = -1.65, 95% CI (-2.02, -1.28), Z = 8.77, p < 0.00001). These results suggested that the treatment group (tongue acupuncture or tongue acupuncture combined with other therapies) was superior to the control group in reducing WST scores and SSA scores. The clinical efficacy of the tongue acupuncture group was better compared with the control group (MD = 3.83, 95% CI (2.61, 5.62), Z = 6.88, p < 0.00001). Conclusion: The meta-analysis showed that the total effective rate of patients with dysphagia after stroke in the treatment group (acupuncture, tongue acupuncture, and acupuncture combined with other therapy) was higher than that in the control group. These results indicated that acupuncture, tongue acupuncture, and acupuncture combined with other therapy can improve post-stroke dysphagia.

Mechanism of Yiqi Huoxue Huatan recipe in the treatment of coronary atherosclerotic disease through network pharmacology and experiments.

In recent years, with population aging and economic development, morbidity and mortality of atherosclerotic cardiovascular disease associated with atherosclerosis (AS) have gradually increased. In this study, a combination of network pharmacology and experimental verification was used to systematically explore the action mechanism of Yiqi Huoxue Huatan Recipe (YHHR) in the treatment of coronary atherosclerotic heart disease (CAD). We searched and screened the active ingredients of Coptis chinensis, Astragalus membranaceus, Salvia miltiorrhiza, and Hirudo. We also searched multiple databases for related target genes corresponding to the compounds and CAD. STRING was used to construct the protein-protein interaction (PPI) network of genes. Metascape was used to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common targets to analyze the main pathways, and finally, the molecular docking and main possible pathways were verified by experimental studies. Firstly, a total of 1480 predicted target points were obtained through the Swiss Target Prediction database. After screening, merging, and deleting duplicate values, a total of 768 targets were obtained. Secondly, "Coronary atherosclerotic heart disease" was searched in databases such as the OMIM, GeneCards, and TTD. 1844 disease-related targets were obtained. Among PPI network diagram of YHHR-CAD, SRC had the highest degree value, followed by AKT1, TP53, hsp90aa1 and mapk3. The KEGG pathway bubble diagram was drawn using Chiplot, the Signal pathways such as NF kappa B signaling pathway, Lipid and AS, and Apelin signaling pathway are closely related to the occurrence of CAD. The PCR and Western blot methods were used to detect the expression of NF-κB p65. When compared with that in the model group, the expression of NF-κB p65mRNA decreased in the low-concentration YHHR group, with P < .05, while the expression of NF-κB p65mRNA decreased significantly in the high-concentration YHHR group, with P < .01. On the other hand, when compared with that in the model group, the expression of NF-κB p65 decreased in the low-concentration YHHR group, but was not statistically significant, while the expression of NF-κB p65 was significant in the high-concentration YHHR group, and has statistical significance with P < .05. YHHR has been shown to resist inflammation and AS through the SRC/NF-κB signaling pathway.

Enhanced encapsulation of lutein using soy protein isolate nanoparticles prepared by pulsed electric field and pH shifting treatment.

In this study, soy protein isolate (SPI) was modified by a pulsed electric field (PEF) combined with pH shifting treatment (10 kV/cm, pH 11) to prepare SPI nanoparticles (PSPI11) for efficient loading of lutein. The results showed that when the mass ratio of SPI to lutein was 25:1, the encapsulation efficiency of lutein in PSPI11 increased from 54% to 77%, and the loading capacity increased by 41% compared to the original SPI. The formed SPI-lutein composite nanoparticles (PSPI11-LUTNPs) had smaller, more homogeneous sizes and larger negative charges than SPI7-LUTNPs. The combined treatment favored the unfolding of the SPI structure and could expose its interior hydrophobic groups to bind with lutein. Nanocomplexation with SPIs significantly improved the solubility and stability of lutein, with PSPI11 showing the greatest improvement. As a result, PEF combined with pH shifting pretreatment is an effective method for developing SPI nanoparticles loaded and protected with lutein.

Fortunilides M-O, anti-inflammatory lindenane sesquiterpenoid dimers from Chloranthus fortunei.

Fortunilides M-O (1-3), three new lindenane-type sesquiterpenoid dimers, together with eighteen known dimers (4-21), were isolated from the roots of Chloranthus fortunei. The structures were determined by their NMR, HRESIMS, ECD data and quantum chemical calculations. All compounds were classical [4 + 2] lindenane-type sesquiterpenoid dimers, in which compounds 2-4 and 16-17 had rare additional carbon­carbon link between C-11 and C-7'. Their anti-inflammatory activity in LPS-induced RAW 264.7 and BV2 microglial cells were screened, and compounds 9 (IC50: 10.70 ± 0.25 µM) and 2 (IC50: 12.26 ± 2.43 µM) showed significant effect, respectively.

Integration of Network Pharmacology and Molecular Docking to Analyse the Mechanism of Action of Oregano Essential Oil in the Treatment of Bovine Mastitis.

The active components, potential targets, and mechanisms of action of oregano essential oil in the treatment of bovine mastitis disease were investigated using network pharmacology and molecular docking approaches. The TCMSP and literature databases were examined for the main compounds in oregano essential oil. Afterward, the physical, chemical, and bioavailability characteristics of the components were evaluated. The PubChem, BATMAN, PharmMapper, and Uniprot databases were utilized to predict the target genes of the major components of oregano essential oil. Via the databases of DrugBank, OMIM, GeneCards, TTD, and DisGenet, the disease targets of bovine mastitis were discovered. We analyzed common targets and built protein-protein interaction (PPI) networks using the STRING database. Key genes were analyzed, obtained, and compound-target-pathway-disease visualization networks were created using Cytoscape. For the GO function and KEGG pathway enrichment analysis, the DAVID database was utilized. Molecular docking via Autodock Tools was utilized to evaluate the reliability of the interactions between oregano essential oil and hub targets. Thymol, carvacrol, and p-cymene are the three major components found in oregano essential oil. The potential targets (TNF, TLR4, ALB, IL-1ß, TLR2, IL-6, IFNG, and MyD88) were screened according to the visual network. The enrichment analysis suggested that the major signaling pathways in network pharmacology may include PI3K-Akt, MAPK, IL-17, and NF-κ B. Molecular docking analysis shows that thymol had good docking activity with TNF, IL-6, and MyD88, carvacrol had good docking activity with TNF, and p-cymene had good docking activity with ALB. This study clarified the mechanism of action of oregano essential oil in the treatment of bovine mastitis, thus providing data supporting the potential for the use of oregano essential oil in the development of new therapeutics for bovine mastitis.

[Effect of Spartina alterniflora Invasion on Soil C:N:P Stoichiometry in Coastal Wetland of Hangzhou Bay].

The invasion of Spartina alterniflora poses a great threat to coastal wetland ecosystems. In this study, the stoichiometric characteristics of soil carbon, nitrogen, and phosphorus under a Spartina alterniflora invasion were explored using ANOVA in a coastal wetland in Hangzhou Bay, and the driving coupling relationship between soil environmental factors and soil C:N:P stoichiometric characteristics of the coastal wetland were further explored based on the redundancy analysis (RDA), boosted regression tree (BRT), and partial least squares-structural equation (PLS-SEM) model. The results showed that:① after the invasion of Spartina alterniflora, soil N:P and total nitrogen (TN) in the wetland increased significantly, and with the increase in invasion time, TN and N:P decreased significantly, whereas soil organic carbon (SOC), C:N, and C:P increased significantly. ② The RDA model revealed that the main factors affecting the stoichiometric characteristics of topsoil C:N:P were SOC>electrical conductivity (EC)>TN in winter and SOC>bulk density (BD)>TN in summer. ③ The BRT model showed that under the invasion of Spartina alterniflora, TN was the key factor affecting soil C:N and N:P, and SOC was the key factor affecting C:P. ④ The PLS-SEM model showed that clay and water content directly affected SOC, thus affecting C:N and C:P; the clay and EC directly affected total phosphorus (TP), thus affecting N:P and C:P; and the EC directly affected TN, thus affecting C:N and N:P. In conclusion, the invasion of Spartina alterniflora had a significant impact on soil C:N:P stoichiometric characteristics in the study area. Soil physical properties and nutrient content directly or indirectly affected soil C:N:P stoichiometric characteristics to varying degrees.

Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation.

Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 µmol·L-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.

Inhibition of Non-small Cell Lung Cancer by Ferroptosis and Apoptosis Induction through P53 and GSK-3ß/Nrf2 Signal Pathways using Qingrehuoxue Formula.

This study aimed to elucidate the effects of Qingrehuoxue Formula (QRHXF) on NSCLC and its underlying mechanisms. Nude mouse model of subcutaneous tumors was established. QRHXF and erastin were administered orally and intraperitoneally, respectively. Mice's body weight and subcutaneous tumor volumes were measured. The effects of QRHXF on epithelial-mesenchymal transition (EMT), tumor-associated angiogenesis and matrix metalloproteinases (MMPs) were assessed. Importantly, we also analysed the anti-NSCLC of QRHXF form the aspect of ferroptosis and apoptosis and investigate its underlying mechanisms. The safety of QRHXF in mice was also evaluated. QRHXF slowed down the speed of tumor growth and visibly inhibited tumor growth. The expression levels of CD31, VEGFA, MMP2 and MMP9 were prominently suppressed by QRHXF. Furthermore, QRHXF appeared to remarkably inhibite cell proliferation and EMT by decreasing Ki67, N-cadherin and vimentin expression but elevating E-cadherin expression. There were more apoptotic cells in QRHXF group's tumor tissues, and QRHXF treatment increased BAX and cleaved-caspased 3 levels but decreased Bcl-2 levels. QRHXF significantly increased the accumulation of ROS, Fe2+, H2O2, and MDA while reduced GSH levels. SLC7A11 and GPX4 protein levels were considerably suppressed by QRHXF treatment. Moreover, QRHXF triggered ultrastructural changes in the mitochondria of tumor cells. The levels of p53 and p-GSK-3ß were upregulated, whereas that of Nrf2 was downregulated in the groups treated with QRHXF. QRHXF displayed no toxicity in mice. QRHXF activated ferroptosis and apoptosis to suppress NSCLC cell progression via p53 and GSK-3ß/Nrf2 signaling pathways.