Research progress of Paris polyphylla in the treatment of digestive tract cancers.

Cancer has become one of the most important causes of human death. In particular, the 5 year survival rate of patients with digestive tract cancer is low. Although chemotherapy drugs have a certain efficacy, they are highly toxic and prone to chemotherapy resistance. With the advancement of antitumor research, many natural drugs have gradually entered basic clinical research. They have low toxicity, few adverse reactions, and play an important synergistic role in the combined targeted therapy of radiotherapy and chemotherapy. A large number of studies have shown that the active components of Paris polyphylla (PPA), a common natural medicinal plant, can play an antitumor role in a variety of digestive tract cancers. In this paper, the main components of PPA such as polyphyllin, C21 steroids, sterols, and flavonoids, amongst others, are introduced, and the mechanisms of action and research progress of PPA and its active components in the treatment of various digestive tract cancers are reviewed and summarized. The main components of PPA have been thoroughly explored to provide more detailed references and innovative ideas for the further development and utilization of similar natural antitumor drugs.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Impact of Cholesterol Metabolism on H2O2-Induced Oxidative Stress Injury in HepG2 Cells Treated with Fatty Acids.

Objective: This study aimed to evaluate the expression of genes involved in cholesterol metabolism and establish their association with oxidative stress (OS). Methods: We employed an in vitro experimental design and cells were divided into six groups: C (control), CH (HepG2 + H2O2), CHN (HepG2 + H2O2 + NAC), F (FFA-treated HepG2), FH (FFA-treated HepG2 + H2O2), and FHN (FFA-treated HepG2 + H2O2 + NAC). Cell viability was assessed using the MTT assay, while successful FFA model establishment was confirmed via Oil Red staining and absorbance. Oxidative stress injury was gauged by measuring ROS, SOD activity, and MDA content. RNA transcription and protein expression of cholesterol-related (DHCR24, DHCR7) and oxidative stress-related (NFE2L2, HMOX1) genes were also examined via RT-qPCR and WB. Results: The impact of H2O2 on cell viability exhibited a time-dose-dependent pattern, paralleling the changes in reactive oxygen species (ROS) levels. Compared to the C group, FFA treatment led to an increase in Oil Red absorption and MDA content and decreased SOD activity. However, it did not result in a significant reduction in cell viability. The FH group exhibited reduced cell viability and SOD activity, along with a further elevation in MDA content compared to the F group. Furthermore, the increased SOD activity and decreased MDA content observed in the CH group were effectively reversed following NAC treatment. Such a reversal was not evident between the FHN and FH groups. Compared to the control group, genes associated with cholesterol metabolism and oxidative stress (OS) displayed heightened expression levels in the other treatment groups, with the FHN group showing lower expression levels than the FH group. Notably, changes in the protein expressions of DHCR24, DHCR7, NFE2L2, and HMOX1 were consistent and exhibited correlations. Conclusions: Cholesterol metabolism emerges as a potential mechanism underlying H2O2-induced oxidative stress injury in HepG2 cells treated with FFA.

Lake eutrophication prediction based on improved MIMO-DD-3Q Learning.

As for the problem that the traditional single depth prediction model has poor strain capacity to the prediction results of time series data when predicting lake eutrophication, this study takes the multi-factor water quality data affecting lake eutrophication as the main research object. A deep reinforcement learning model is proposed, which can realize the mutual conversion of water quality data prediction models at different times, select the optimal prediction strategy of lake eutrophication at the current time according to its own continuous learning, and improve the reinforcement learning algorithm. Firstly, the greedy factor, the fixed parameter of Agent learning training in reinforcement learning, is introduced into an arctangent function and the mean value reward factor is defined. On this basis, three Q estimates are introduced, and the weight parameters are obtained by calculating the realistic value of Q, taking the average value and the minimum value to update the final Q table, so as to get an Improved MIMO-DD-3Q Learning model. The preliminary prediction results of lake eutrophication are obtained, and the errors obtained are used as the secondary input to continue updating the Q table to build the final Improved MIMO-DD-3Q Learning model, so as to achieve the final prediction of water eutrophication. In this study, multi-factor water quality data of Yongding River in Beijing were selected from 0:00 on July 26, 2021 to 0:00 on September 5, 2021. Firstly, data smoothing and principal component analysis were carried out to confirm that there was a certain correlation between all factors in the occurrence of lake eutrophication. Then, the Improved MIMO-DD-3Q Learning prediction model was used for experimental verification. The results show that the Improved MIMO-DD-3Q Learning model has a good effect in the field of lake eutrophication prediction.

Chitosan functionalized gold nanostars as a theranostic platform for intracellular microRNA detection and photothermal therapy.

The development of a theranostic platform that integrates both diagnostic and therapeutic capabilities is in great need for precise and personalized medicine. Here, we present a novel nanoplatform (AuNS@CS-hpDNA) formulated by chitosan functionalized gold nanostar composites and further complexed with fluorescent hairpin DNA (hpDNA) probes for tumor-related miRNA imaging and photothermal therapy (PTT). The optimized AuNS@CS-hpDNA nanoplatform mediated efficient hpDNA probe loading and intracellular delivery. Subsequently, the cytosol transfer of the hpDNA probe enabled specific hybridization using the targeted miRNA, which triggered the recovery of fluorescence for the precise detection of biomarker miR21 in living cells and realized the distinguishing cancer cell line MCF-7 and normal cells. Meanwhile, the AuNS@CS-hpDNA nanoplatform exhibited excellent photothermal conversion properties, which induced efficient cancer cell killing under laser irradiation. Thus, the developed AuNS@CS-hpDNA nanoplatform could simultaneously realize the precise detection of cancer cells and accurately initiate efficient PTT, which represents a promising strategy for precise cancer therapy.

Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study.

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30-0.98, Ptrend = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.

Serum selenium, selenoprotein P, and glutathione peroxidase 3 during early and late pregnancy in association with gestational diabetes mellitus: Prospective Odense Child Cohort.

BACKGROUND: Diet is an important modifiable risk factor for gestational diabetes mellitus (GDM) and its related complications; however, the role of essential micronutrients such as selenium (Se), particularly in populations with low Se intake, is inconclusive. OBJECTIVES: The aim was to investigate the association of 3 established biomarkers of Se status with GDM, gestational glucose metabolism, and large for gestational-age offspring. METHODS: This study included 1346 pregnant females with 2294 serum samples from the prospective, population-based Odense Child Cohort study, Denmark. Serum Se, selenoprotein P (SELENOP) concentrations, and glutathione peroxidase 3 (GPX3) activity were measured in early and late pregnancy, and fasting glucose and insulin assessments in late pregnancy. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated, and the GDM definition was according to the WHO 2013 threshold of fasting venous plasma glucose of ≥5.1 mmol/L. A subcohort underwent an oral glucose tolerance test. Regression models adjusted for various confounders quantified dose-dependent associations. RESULTS: Se and SELENOP declined during pregnancy. There were dose-dependent inverse associations of early GPX3 with late pregnancy GDM (WHO 2013), fasting glucose, insulin, HOMA-IR, and 2 h glucose. The odds ratio (OR) of GDM was 0.33 (95% CI: 0.16, 0.65) for 1 log-scale-increment in early GPX3 activity. Late pregnancy GPX3 and SELENOP were inversely associated with GDM and HOMA-IR; the OR of GDM was 0.21 (95% CI: 0.12, 0.38) and 0.52 (95% CI: 0.35, 0.77), for 1 log-scale-increment of GPX3 and SELENOP, respectively. A decline in Se biomarkers during pregnancy was associated with a higher risk of GDM and higher HOMA-IR. Low GPX3 activity in late pregnancy was associated with a higher risk of large for gestational-age offspring, partly (∼20%) mediated by fasting glucose concentrations (P = 0.006). CONCLUSIONS: Low serum Se in pregnancy, particularly GPX3 activity, is independently associated with risk of GDM and large for gestational age. Offering Se status assessment in pregnancy identifies females at high risk for GDM who may benefit from Se substitution.

Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study.

INTRODUCTION: Low serum selenium and altered tumour RNA expression of certain selenoproteins are associated with a poor breast cancer prognosis. Selenoprotein expression stringently depends on selenium availability, hence circulating selenium may interact with tumour selenoprotein expression. However, there is no matched analysis to date. METHODS: This study included 1453 patients with newly diagnosed breast cancer from the multicentric prospective Sweden Cancerome Analysis Network - Breast study. Total serum selenium, selenoprotein P and glutathione peroxidase 3 were analysed at time of diagnosis. Bulk RNA-sequencing was conducted in matched tumour tissues. Fully adjusted Cox regression models with an interaction term were employed to detect dose-dependent interactions of circulating selenium with the associations of tumour selenoprotein mRNA expression and mortality. RESULTS: 237 deaths were recorded within ~ 9 years follow-up. All three serum selenium biomarkers correlated positively (p < 0.001). All selenoproteins except for GPX6 were expressed in tumour tissues. Single cell RNA-sequencing revealed a heterogeneous expression pattern in the tumour microenvironment. Circulating selenium correlated positively with tumour SELENOW and SELENON expression (p < 0.001). In fully adjusted models, the associations of DIO1, DIO3 and SELENOM with mortality were dose-dependently modified by serum selenium (p < 0.001, p = 0.020, p = 0.038, respectively). With increasing selenium, DIO1 and SELENOM associated with lower, whereas DIO3 expression associated with higher mortality. Association of DIO1 with lower mortality was only apparent in patients with high selenium [above median (70.36 µg/L)], and the HR (95%CI) for one-unit increase in log(FPKM + 1) was 0.70 (0.50-0.98). CONCLUSIONS: This first unbiased analysis of serum selenium with the breast cancer selenotranscriptome identified an effect-modification of selenium on the associations of DIO1, SELENOM, and DIO3 with prognosis. Selenium substitution in patients with DIO1-expressing tumours merits consideration to improve survival.

Are Twin Pregnancies at Higher Risk for Iron and Calcium Deficiency than Singleton Pregnancies?

The aim of this study was to compare the iron and calcium status in singleton and twin pregnancies and to assess whether there is an increased risk for iron and calcium deficiency in twin gestation. The study included 105 singleton and 9 twin pregnancies at or above 35 weeks of gestation. Information on prenatal supplementation with iron or calcium was acquired, and adverse perinatal outcomes were recorded. Biosamples from all 114 mothers and 73 newborns (61 singleton and 12 twin newborns) were finally analyzed. Total iron and calcium concentrations in serum were measured through total reflection X-ray fluorescence analysis. The results indicated no significant differences in maternal serum iron and calcium concentrations between singleton and twin pregnancies. Similarly, iron and calcium concentrations in newborn umbilical cord serum samples were not different between singleton and twin pregnancies. The comparison of total iron and calcium between mothers and umbilical cord serum indicated significantly lower concentrations in the mothers, with the differences being not homogenous but rather pair-specific. A significant positive correlation between maternal serum and umbilical cord serum calcium concentration was noticed. Prenatal iron supplementation was associated with higher iron concentrations in both mothers and newborns, supporting the efficiency of supplementation and the quality of the study methods. Collectively, the data indicate no significant differences in serum iron and calcium concentrations with regard to singleton or twin pregnancies and the efficiency of iron supplementation during pregnancy for increasing iron status.

Green Social Prescribing in Practice: A Case Study of Walsall, UK.

This paper presents a case study of Green Social Prescribing (GSP) in Walsall, a medium-sized urban area located in the West Midlands, UK. GSP is a means of enabling health professionals to refer people to a range of local non-clinical nature-based activities, e.g., community gardening and conservation volunteering. As a new practice to address multiple challenges in health and sustainability, GSP has been promoted by the UK government and the NHS in the past few years. There is as yet limited evidence and knowledge about how this approach is implemented at a local level. This paper addresses this gap of knowledge, by exploring how GSP is implemented in Walsall as a case study. Based on extensive engagement and research activities with the local partners to collect data, this paper reveals the local contexts of GSP, the referral pathways, and people's lived experience, discussing the challenges, barriers, and opportunities in delivering GSP at the local level. This study suggests that a more collaborative and genuine place-based approach is essential, and alongside GSP, investment into infrastructure is needed to move the health paradigm further from 'prevention' to 'promotion' so that more people can benefit from what nature can offer.

Myofascial acupuncture versus routine acupuncture for mechanical neck pain: a protocol for a multicentre randomised controlled trial.

INTRODUCTION: Mechanical neck pain (MNP) is defined as pain in the area of the neck and/or neck-shoulder provoked by body mechanics and which adversely affects physical, psychological and social function. The treatments for MNP are limited. Previous studies and clinical experience have indicated that myofascial acupuncture might be a better treatment option for MNP, but the efficacy is controversial. Therefore, our aim is to compare the efficacy of myofascial acupuncture and routine acupuncture for MNP. METHODS AND ANALYSIS: The study is a multicentre, prospective randomised clinical trial. Patients will be recruited from four tertiary hospitals in China. A total of 438 participants with MNP will be randomly assigned into two groups, namely the 'Sancai-Tianbu' myofascial acupuncture group and the routine acupuncture group, at a ratio of 1:1. Each group will receive the acupuncture treatment twice a week for 21 days, totalling six sessions. The primary outcome will be the Visual Analogue Scale score. The secondary outcomes will be the Neck Disability Index, the cervical range of motion and the MOS 36-Item Short Form Health Survey. The assessments will be performed at baseline (immediately after allocation), pretreatment (5 min before every treatment), post-treatment (within 10 min after every treatment), postcourse (within 1 day after the course), and at 1, 3 and 6 months after the course. All patients will be included in the intent-to-treat analysis. Repeated-measure analysis of covariance will be used to determine the effects of the intervention on the outcome measures. ETHICS AND DISSEMINATION: Ethics approval was obtained from China Aerospace Science & Industry Corporation 731 Hospital, with permission number 2022-0204-01. Written informed consent will be obtained from the enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2200061453.

Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone.

Chronic Fatigue Syndrome (CFS) presents with symptoms of hypothyroidism, including mental and physical fatigue, poor sleep, depression, and anxiety. However, thyroid hormone (TH) profiles of elevated thyrotropin and low thyroxine (T4) are not consistently observed. Recently, autoantibodies to the Se transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto's thyroiditis and shown to impair selenoprotein expression. We hypothesized that SELENOP-aAb are prevalent in CFS, and associate with reduced selenoprotein expression and impaired TH deiodination. Se status and SELENOP-aAb prevalence was compared by combining European CFS patients (n = 167) and healthy controls (n = 545) from different sources. The biomarkers total Se, glutathione peroxidase (GPx3) and SELENOP showed linear correlations across the samples without reaching saturation, indicative of Se deficiency. SELENOP-aAb prevalence was 9.6-15.6% in CFS versus 0.9-2.0% in controls, depending on cut-off for positivity. The linear correlation between Se and GPx3 activity was absent in SELENOP-aAb positive patients, suggesting impaired Se supply of kidney. A subgroup of paired control (n = 119) and CSF (n = 111) patients had been characterized for TH and biochemical parameters before. Within this subgroup, SELENOP-aAb positive patients displayed particularly low deiodinase activity (SPINA-GD index), free T3 levels, total T3 to total T4 (TT3/TT4) and free T3 to free T4 (FT3/FT4) ratios. In 24 h urine, iodine concentrations were significantly lower in SELENOP-aAb positive than in SELENOP-aAb negative patients or controls (median (IQR); 43.2 (16.0) vs. 58.9 (45.2) vs. 89.0 (54.9) µg/L). The data indicate that SELENOP-aAb associate with low deiodination rate and reduced activation of TH to active T3. We conclude that a subset of CFS patients express SELENOP-aAb that disturb Se transport and reduce selenoprotein expression in target tissues. Hereby, TH activation decreases as an acquired condition not reflected by thyrotropin and T4 in blood. This hypothesis opens new diagnostic and therapeutic options for SELENOP-aAb positive CFS, but requires clinical evidence from intervention trials.

Inhibitory Effect of Tea Saponin on Major Apple-Disease-Inducing Fungi.

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.

Transcriptomics Insights into Phosphorus Stress Response of Myriophyllum aquaticum.

Through excellent absorption and transformation, the macrophyte Myriophyllum (M.) aquaticum can considerably remove phosphorus from wastewater. The results of changes in growth rate, chlorophyll content, and roots number and length showed that M. aquaticum could cope better with high phosphorus stress compared with low phosphorus stress. Transcriptome and differentially expressed genes (DEGs) analyses revealed that, when exposed to phosphorus stresses at various concentrations, the roots were more active than the leaves, with more DEGs regulated. M. aquaticum also showed different gene expression and pathway regulatory patterns when exposed to low phosphorus and high phosphorus stresses. M. aquaticum's capacity to cope with phosphorus stress was maybe due to its improved ability to regulate metabolic pathways such as photosynthesis, oxidative stress reduction, phosphorus metabolism, signal transduction, secondary metabolites biosynthesis, and energy metabolism. In general, M. aquaticum has a complex and interconnected regulatory network that deals efficiently with phosphorus stress to varying degrees. This is the first time that the mechanisms of M. aquaticum in sustaining phosphorus stress have been fully examined at the transcriptome level using high-throughput sequencing analysis, which may indicate the direction of follow-up research and have some guiding value for its future applications.

Investigation of pharmacodynamic material basis of Anemarrhenae Rhizoma and its processed products based on plant metabolomics and molecular docking technology.

RATIONALE: Anemarrhenae Rhizoma (AR) has been an often used traditional Chinese medicine (TCM) for a long time. Its salt-processed form is one of the most common application forms. Modern pharmacological research has shown that the salt-processed product has various significantly enhanced pharmacological activities. However, the pharmacodynamic material basis of this change is not yet known. The aim of this study was to develop a strategy to screen pharmacodynamic substances in AR and salt-processed AR (SAR). METHODS: An integrated strategy combining plant metabolomics with molecular docking technology was established to screen pharmacodynamic substances. The plant metabolomics analysis was performed to select the chemical markers between AR and SAR. Then, molecular docking technology was applied to explore the relationship between chemical markers and diabetes targets (α-glucosidase). Finally, potential quality control markers were screened. RESULTS: There were significant differences in the quantification of nine steroidal saponins between AR and SAR. The results of plant metabolomics analysis showed a quite clear discrimination including 29 chemical markers between AR and SAR. Taking the hypoglycemic activity into consideration, 16 steroidal saponins were selected as potential quality markers. CONCLUSIONS: The developed method not only supplied an optional solution to search for pharmacophores in AR and SAR, but also provided a foundation for the study of the differential components and pharmacodynamics in various processed products of TCMs.

The effects of mindfulness-based interventions on nurses' anxiety and depression: A meta-analysis.

OBJECTIVE: This meta-analysis aimed to determine the effect of mindfulness interventions on nurses' levels of depression and anxiety. DESIGN: Meta-analysis of randomised controlled trials. METHODS: The following Chinese and English databases were searched: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI). The retrieval period was from database construction to 30 March 2022. Two researchers screened the relevant literature and extracted the data. After a cross-check, data were input into Stata version 16.0 for meta-analysis. RESULTS: Twelve randomised controlled trials from 2017 to 2021 were included, which involved 807 subjects (405 and 402 in the intervention and control groups, respectively). Meta-analysis results showed that nurses' anxiety reduced by mindfulness-based interventions was significantly higher compared to that of the control group (SMD = 0.91, 95% CI: 0.27-1.55, p < 0.05). Furthermore, an 8-week mindfulness-based intervention (SMD = 1.43, 95% CI: 0.61-2.24) reduced the level of anxiety significantly more compared to a 4-week intervention (SMD = 1.03, 95% CI: 0.36-1.71). Mindfulness-based interventions were better compared to conventional intervention to reduce the level of depression (SMD = 1.02, 95% CI: 0.42-1.61, p < 0.05), and an 8-week mindfulness intervention (SMD = 1.81, 95% CI: 0.78-2.84) reduced the level of depression significantly more compared to a 4-week intervention (SMD = 0.82, 95% CI: 0.29-1.35). Since limited studies had interventions longer than 8 weeks, results on longer mindfulness interventions in reducing nurses' anxiety and depression are inconclusive. In conclusion, mindfulness intervention for 8 weeks or less can significantly reduce nurses' anxiety and depression levels. PATIENT OR PUBLIC CONTRIBUTION: None.

High throughput drug screening identifies resveratrol as suppressor of hepatic SELENOP expression.

INTRODUCTION: Selenium (Se) is an essential trace element that exerts its effects mainly as the proteinogenic amino acid selenocysteine within a small set of selenoproteins. Among all family members, selenoprotein P (SELENOP) constitutes a particularly interesting protein as it serves as a biomarker and serum Se transporter from liver to privileged tissues. SELENOP expression is tightly regulated by dietary Se intake, inflammation, hypoxia and certain substances, but a systematic drug screening has hitherto not been performed. METHODS: A compound library of 1861 FDA approved clinically relevant drugs was systematically screened for interfering effects on SELENOP expression in HepG2 cells using a validated ELISA method. Dilution experiments were conducted to characterize dose-responses. A most potent SELENOP inhibitor was further characterized by RNA-seq analysis to assess effect-associated biochemical pathways. RESULTS: Applying a 2-fold change threshold, 236 modulators of SELENOP expression were identified. All initial hits were replicated as biological triplicates and analyzed for effects on cell viability. A set of 38 drugs suppressed SELENOP expression more than three-fold, among which were cancer drugs, immunosuppressants, anti-infectious drugs, nutritional supplements and others. Considering a 90% cell viability threshold, resveratrol, vidofludimus, and antimony potassium-tartrate were the most potent substances with suppressive effects on extracellular SELENOP concentrations. Resveratrol suppressed SELENOP levels dose-dependently in a concentration range from 0.8 µM to 50.0 µM, without affecting cell viability, along with strong effects on key genes controlling metabolic pathways and vesicle trafficking. CONCLUSION: The results highlight an unexpected direct effect of the plant stilbenoid resveratrol, known for its antioxidative and health-promoting effects, on the central Se transport protein. The suppressive effects on SELENOP may increase liver Se levels and intracellular selenoprotein expression, thereby conferring additional protection to hepatocytes at the expense of systemic Se transport. Further physiological effects from this interaction require analyses in vivo and by clinical studies.

Phillygenin from Forsythia suspensa leaves exhibits analgesic potential and anti-inflammatory activity in carrageenan-induced paw edema in mice.

Forsythia suspensa (Thunb.) Vahl (Oleaceae) leaves are valuable sources of phillygenin. This study aimed to isolate phillygenin from F. suspensa leaves and examine its analgesic and anti-inflammatory effects. Phillygenin was successfully extracted and isolated from F. suspensa leaves after fermentation. Phillygenin significantly reduced the number of writhing induced by acetic acid, prolonged the latency period in the hot plate test, and inhibited the xylene-induced ear edema and carrageenan-induced paw edema in mice. IL-6, TNF-α, IL-1ß, NO, and PGE2 levels in the carrageenan-induced paw edema were notably reduced after pretreatment with phillygenin. Phillygenin significantly decreased the iNOS and COX-2 protein expressions and the IκB-α and NF-κB p65 phosphorylation. This study demonstrated that phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders. The study contributes to the comprehensive development and utilization of F. suspensa leaves for economic and health care. PRACTICAL APPLICATIONS: Phillygenin is one of the major active ingredients in Forsythia suspensa. But the content of phillygenin in F. suspensa is very low which limits its application. Phillygenin has potential pharmacological activity and anti-inflammatory properties. However, the potential effects of phillygenin on analgesic activity have not been clarified. Furthermore, the data on its anti-inflammatory activity in vivo are relatively limited. This study evaluated the analgesic activity for the first time and the acute anti-inflammatory effect of phillygenin from F. suspensa leaves by fermentation, which indicated phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders.

Effect of electroacupuncture on cyclic adenosine monophosphate-protein kinase A-vanillic acid receptor subtype 1 of the transient receptor potential/PLK-protein kinase C-vanillic acid receptor subtype 1 of the transient receptor potential pathway based on RNA-seq analysis in prostate tissue in rats with chronic prostatitis/chronic pelvic pain syndrome.

Objective: To investigate the analgesic mechanism of electroacupuncture (EA) in rats with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: Thirty male SD rats were randomly divided into sham group, model group and EA group, with ten rats in each group. The CP/CPPS model was prepared by injecting 50 µL of complete Freund's adjuvant (CFA) into the ventral lobes of the prostate tissue, and the sham group was injected with the same dose of saline. After 14 days of modeling, EA was applied to Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) in the EA group. After four courses, H&E staining was performed to observe the prostate tissue morphology, transcriptome sequencing (RNA-Seq) was performed for each group, and the selected signaling pathways were verified by qRT-PCR. Results: The RNA-Seq analysis results suggested that the analgesic effect of EA on CP/CPPS may be achieved by regulating prostate gene expression, which may be related to multiple biological processes and signaling pathways. qRT-PCR results showed that the vanillic acid receptor subtype 1 of the transient receptor potential (TRPV1), phospholipase C (PLC), protein kinase C (PKC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were all upregulated in the model group compared to the sham group (p < 0.01). Compared with the model group, TRPV1, PLC, PKC, cAMP, and PKA were all downregulated in the EA group (p < 0.05, p < 0.01). Conclusion: The analgesic mechanism of EA on CP/CPPS may be achieved through modulation of cAMP-PKA-TRPV1/PLC-PKC-TRPV1 signaling pathway.

Selenium Status and Supplementation Effects in Pregnancy-A Study on Mother-Child Pairs from a Single-Center Cohort.

The demand for selenium (Se) increases during pregnancy since this element supports child growth, proper neuronal development and maternal thyroid function. The issue is particularly relevant for populations living in areas with a limited selenium supply, where many pregnant women opt for Se supplementation. The efficiency of this measure is unknown, although it seems vital in the prevention of severe Se deficiency. In order to evaluate this hypothesis, an observational study was conducted in Poland, where Se deficiency is prevalent. Pregnant women were invited to participate in the study and provided serum samples at the end of pregnancy (n = 115). Information on the supplemental intake of micronutrients was recorded in a face-to-face interview. In addition, serum samples were isolated from the cord blood of newborns at delivery (n = 112) and included in the analyses. Thyroid hormone status was evaluated by routine laboratory tests, and Se status was determined by total Se and selenoprotein P (SELENOP) concentrations and extracellular glutathione peroxidase (GPX3) activity. The three parameters of Se status correlated strongly within the group of mothers and within the group of newborns, with an additional significant correlation found among mother-child pairs. One-third of mothers reported additional Se intake, mainly as a component of multi-micronutrient supplements, at a mean (±SD) dosage of 42 ± 14 µg Se/day. Despite this regime, most of the women presented an insufficient Se status, with 79% of mothers displaying serum Se concentrations below 70 µg/L (indicating Se deficiency) and 22% showing levels below 45.9 µg/L (severe Se deficiency). The inadequate Se supply was also reflected in relatively low SELENOP concentrations and GPX3 activity. Neither total Se nor SELENOP or GPX3 levels were significantly higher in the group of mothers reporting the intake of supplements than in the non-supplementing group. Nevertheless, elevated SELENOP concentrations were observed in the subgroup receiving supplements with more than 55 µg/day. We conclude that the self-administered supplementation of small Se dosages was not sufficient to achieve replete Se status in the micronutrient scant area. However, the maternal Se deficit measured by either Se, SELENOP or GPX3 was transferred from mothers to the newborns, as the parameters correlated strongly in the mother-newborn pairs of samples. It is vital to re-evaluate the guidelines concerning pregnancy care and monitoring of micronutrient status during pregnancy, in particular in areas where deficiencies are present.