Asiatic acid and madecassic acid cause cardiotoxicity via inflammation and production of excessive reactive oxygen species in zebrafish.

Centella asiatica (L.) Urban is a famous Chinese traditional medicine, which is widely used for treating various chronic inflammatory diseases. Although there are reports that Centella total glycosides exhibit heart-protective properties, our previous experiment showed that it has cardiac toxic effects in zebrafish. The components of Centella total glycosides are complex, so we recommend further research to determine their key components and mechanisms. In this study, sample quantification was done using liquid chromatography-tandem mass spectrometry. The cardiotoxicity of Centella total glycosides, asiaticoside, madecassoside, asiatic acid, and madecassic acid was evaluated using zebrafish and cell models. The zebrafish oxidative stress model and myocarditis model were used to explore further the mechanisms through which cardiotoxicity is achieved. Asiatic acid and madecassic acid caused zebrafish cardiotoxicity and H9C2 cell death. However, no toxicity effects were observed for asiaticoside and madecassoside in zebrafish, until the solution was saturated. The results from the cell model study showed that asiatic acid and madecassic acid changed the expression of apoptosis-related genes in myocardial cells. In the zebrafish model, high concentrations of these components raised the levels of induced systemic inflammation, neutrophils gathered in the heart, and oxidative stress injury. Asiatic acid and madecassic acid are the main components causing cardiotoxicity in zebrafish. This may be due to enhanced inflammation and reactive oxygen species injury, which causes myocardial cell apoptosis, which further leads to cardiac toxicity.

Intracellular Magnetic Hyperthermia Enables Concurrent Down-Regulation of CD47 and SIRPα To Potentiate Antitumor Immunity.

Harnessing the potential of tumor-associated macrophages (TAMs) to engulf tumor cells offers promising avenues for cancer therapy. Targeting phagocytosis checkpoints, particularly the CD47-signal regulatory protein α (SIRPα) axis, is crucial for modulating TAM activity. However, single checkpoint inhibition has shown a limited efficacy. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-mediated magnetic hyperthermia effectively suppresses the expression of CD47 protein on Hepa1-6 tumor cells and SIRPα receptor on macrophages, which disrupts CD47-SIRPα interaction. FVIO-mediated magnetic hyperthermia also induces immunogenic cell death and polarizes TAMs toward M1 phenotype. These changes collectively bolster the phagocytic ability of macrophages to eliminate tumor cells. Furthermore, FVIO-mediated magnetic hyperthermia concurrently escalates cytotoxic T lymphocyte levels and diminishes regulatory T cell levels. Our findings reveal that magnetic hyperthermia offers a novel approach for dual down-regulation of CD47 and SIRPα, reshaping the tumor microenvironment to stimulate immune responses, culminating in significant antitumor activity.

Recent pharmacological advances in the treatment of cardiovascular events with Astragaloside IV.

Cardiovascular disease (CVD) remains the leading cause of death and disability globally. A wide range of CVDs have been reported, each of which diverges significantly, exhibiting sophisticated types of pathogenesis (e.g., inflammatory, oxidative stress, and disorders in cardiomyocyte metabolism). Compared with conventional treatments in modern medicine, traditional Chinese medicine (TCM) can exhibit comparative advantages in the treatment of CVDs. TCM can be utilized to develop effective strategies for addressing the challenges of CVD, with fewer side effects and higher therapeutic efficiency. Astragaloside IV (AS-IV) has been confirmed as one of the major active ingredients found in Astragalus membranaceus (a Chinese herbal medicine that has been extensively employed clinically for the treatments of CVDs). Since recent studies have shown that AS-IV in CVD treatments has achieved promising results, the substance has aroused great attention and further discussions in the field. The present review aims to summarize the recent pharmacological advances in employing AS-IV in the treatment of CVDs.

Clinical Efficacy of Medical Dextrose Tincture Liquid in the Treatment of Facial Photoaging.

INTRODUCTION: Exogenous aging mainly refers to photo-aging, which is caused by environmental factors including ultraviolet exposure. Dextran is a homopolysaccharide composed of glucose as monosaccharide, and glucose units are connected by glycosidic bonds. OBJECTIVES: The purpose of this study was to explore the clinical efficacy of medical dextrose tincture liquid (medical dextrose tincture) in the treatment of facial photoaging. METHODS: Thirty-four volunteers were included in the randomized double-blind study. According to the random number table method, the subjects were randomized into control and treatment groups. The subjects in the control and treatment groups were treated with medical hyaluronic acid gel and medical dextrose tincture, respectively. They received mesotherapy therapy three times with an interval of 28 days between treatments. Video image acquisition was performed before treatment and 28 days after treatment. Skin moisture content, glossiness, heme content, collagen density, and elasticity were tested. The subjective evaluations of subjects and doctors before and after treatment were compared. RESULTS: Compared with the pre-treatment baseline, medical dextran tincture significantly increased skin moisture retention, skin gloss, and skin collagen density (p<0.001). Additionally, the skin retraction time was significantly reduced, and the skin retraction time was also markedly decreased after treatment with medical dextran tincture (p<0.001). The effects of medical dextran tincture were more significant in comparison with medical hyaluronic acid gel (p<0.05). The subjective evaluation results of doctors showed that after 84 days of treatment, the overall skin photoaging score was significantly reduced (p<0.001). The subjective evaluation results of volunteers showed that the various skin problems of more than 50% of volunteers were improved after treatment. CONCLUSION: Medical dextran tincture has obvious effects of moisturizing, increasing luster, improving skin redness, increasing skin collagen content and enhancing skin elasticity.

The relationship between trait mindfulness and resilience: A meta-analysis.

Resilience is a positive psychological resource that promotes health. Trait mindfulness was found to be related to resilience. However, previous studies on this relationship have shown contradictory results. The current meta-analysis explored the relationship between trait mindfulness and resilience based on a three-level random-effects meta-analysis model. A significant and positive relationship between trait mindfulness and resilience (r = 0.385; p < 0.0001) was revealed by analyzing 197 effect sizes from 103 studies. Furthermore, the subsequent moderator analysis found that the facet of mindfulness (e.g., awareness, nonjudging) (F(6, 190) = 6.181; p < 0.001), measurement of mindfulness (e.g., the Mindful Attention Awareness Scale) (F(7, 191) = 4.758; p < 0.001), aspect of resilience (e.g., family resilience) (F(5, 191) = 3.455; p < 0.05), measurement of resilience (e.g., the Connor-Davidson Resilience Scale) (F(11, 185) = 2.256; p < 0.05), and age (F(1, 150) = 4.588; p < 0.05) acted as significant moderators. Overall, this study confirmed the positive relationship between trait mindfulness and resilience, suggesting that people with higher levels of trait mindfulness were more likely to have higher levels of resilience. The current findings provided insightful information for interventions targeted at improving resilience.

Developing occupational and health susceptibility personas for wastewater personnel in the United States in the age of COVID-19.

Compared with the public, wastewater personnel, are at an increased risk of infection and illness from wastewater pathogens due to work-related tasks. Unfortunately, current risk assessment approaches do not consider individual personnel factors (e.g., age and health conditions) that may influence their susceptibility to a health effect. The objective of this study is to establish a baseline level of occupational and health factors among the wastewater personnel population, quantify these factors using a susceptibility evaluation scoring system, and examine relevant susceptibility features using the concept of "Personas." Using survey data from 246 respondents and public health risk data on COVID-19 from the CDC, personnel clustered into three persona groups: "low susceptibility," "high occupational susceptibility," and "high health susceptibility." Results highlight the intersectionality between gender, age, underlying health conditions, job tasks, and level of exposure to wastewater and provide context for incorporating individual variables into risk assessment methodologies with the goal of protecting this essential workforce. PRACTITIONER POINTS: A risk assessment framework that combines health and occupational susceptibility factors was developed for wastewater treatment plant personnel. Wastewater personnel clustered into three persona groups: "low susceptibility," "high occupational susceptibility," and "high health susceptibility." The intersectionality between job related activities and individual health provides a holistic approach to risk assessment for wastewater personnel.

Enhancement of CD8+ T-Cell-Mediated Tumor Immunotherapy via Magnetic Hyperthermia.

Magnetic hyperthermia (MHT) uses magnetic iron oxide nanoparticles (MIONs) to irradiate heat when subjected to an alternating magnetic field (AMF), which then trigger a series of biological effects to realize rapid tumor-killing effects. With the deepening in research, MHT has also shown significant potential in achieving antitumor immunity. On the other hand, immunotherapy in cancer treatment has gained increasing attention over recent years and excellent results have generally been reported. Using MHT to activate antitumor immunity and clarifying its synergistic mechanism, i. e., immunogenic cell death (ICD) and immunosuppressive tumor microenvironment (TME) reversal, can achieve a synergistically enhanced therapeutic effect on primary tumors and metastatic lesions, and this can prevent cancer recurrence and metastasis, which thus prolong survival. In this review, we discussed the role of MHT when utilized alone and combining MHT with other treatments (such as radiotherapy, photodynamic therapy, and immune checkpoint blockers) in the process of tumor immunotherapy, including antigen release, dendritic cells (DCs) maturation, and activation of CD8+ cytotoxic T lymphocytes. Finally, the challenges and future development of current MHT and immunotherapy are discussed.

Excessive Vitamin A Supplementation Increased the Incidence of Acute Respiratory Tract Infections: A Systematic Review and Meta-Analysis.

(1) Background: vitamin A deficiency (VAD) is highly prevalent in children living in poor conditions. It has been suggested that vitamin A supplementation (VAS) may reduce the risk of acute respiratory tract infections (ARTI). Our study provides updates on the effects of oral VAS (alone) in children on ARTI and further explores the effect on interesting subgroups. (2) Methods: eight databases were systematically searched from their inception until 5 July 2021. The assessments of inclusion criteria, extraction of data, and data synthesis were carried out independently by two reviewers. (3) Results: a total of 26 randomized trials involving 50,944 participants fulfilled the inclusion criteria. There was no significant association of VAS with the incidence of ARTI compared with the placebo (RR 1.03, 95% CI 0.92 to 1.15). Subgroup analyses showed that VAS higher than WHO recommendations increased the incidence of ARTI by 13% (RR 1.13, 95% CI 1.07 to 1.20), and in the high-dose intervention group, the incidence rate among well-nourished children rose by 66% (RR 1.66, 95% CI 1.30 to 2.11). (4) Conclusions: no more beneficial effects were seen with VAS in children in the prevention or recovery of acute respiratory infections. Excessive VAS may increase the incidence of ARTI in children with normal nutritional status.

Effect of aromatherapy on preoperative anxiety in adult patients: A meta-analysis of randomized controlled trials.

BACKGROUND: and purpose: Preoperative anxiety is an important factor for postoperative complications, and many patients are using aromatherapy to relieve preoperative anxiety. This study aimed to evaluate the effect of aromatherapy on preoperative anxiety in adult patients. METHODS: An electronic search of six databases (Cochrane Library, PubMed, Embase, CINAHL, CNKI, and WanFang Data) was conducted for full-text publications of trials published from the inception of the databases to February 20, 2020. All randomized controlled trials (RCTs) where aromatherapy was used for treatment of preoperative anxiety were included. Interventions included all types of aromatherapy compared to standard care or placebo. The primary outcome was self-rated anxiety and the secondary outcome was adverse effect. Two researchers independently screened and extracted relevant data. A random-effects model was utilized to calculate the effect size as mean difference (MD). RESULTS: Our search retrieved 347 records. Thirteen trials were included for qualitative analysis, of which ten RCTs with 750 patients were included for meta-analysis. Most studies had a high or unclear selection and performance bias. Overall, aromatherapy was found to decrease preoperative anxiety significantly compared to the control group (MD = -3.95, 95%CI [-6.36, -1.53], P = 0.001). According to subgroup analysis, most subgroups showed a significant effect of aromatherapy on preoperative anxiety, except for the no treatment subgroup (MD: 5.40, 95%CI: 7.76 to 0.71) and female subgroup (MD: 3.96, 95%CI: 9.19 to 1.27). CONCLUSION: Aromatherapy may be an effective complementary treatment for preoperative anxiety. Nevertheless, due to methodological limitations of the included trials, further studies with strict control of the research design are required for firm recommendations.

Identification and pharmacokinetics of saponins in Rhizoma Anemarrhenae after oral administration to rats by HPLC-Q-TOF/MS and HPLC-MS/MS.

Rhizoma Anemarrhenae is a well-known herbal medicine with saponins as its commonly regarded major bioactive components. It is essential to classify the properties of saponins which are associated with their toxicity and efficacy. In this study, 25 compounds were identified by HPLC-Q-TOF/MS in the extract of Rhizoma Anemarrhenae and 8 saponins were detected in rat plasma by HPLC-MS/MS after oral administration of this extract. These were neomangiferin, mangiferin, timosaponin E1, timosaponin E, timosaponin B-II, timosaponin B-III, timosaponin A-III and timosaponin A-I. A sensitive and accurate HPLC-MS/MS method was developed and successfully applied to a pharmacokinetic study of the abovementioned eight saponins after oral administration of the Rhizoma Anemarrhenae extract to rats. The method validation, including specificity, linearity, precision, accuracy, recovery, matrix effect and robustness, met the requirements of the intended use. The pharmacokinetic parameter, T max value, ranged from 2 to 8 h for these eight saponins whereas their elimination half-life (t 1/2) ranged from 4.06 to 9.77 h, indicating slow excretion. The plasma concentrations of these eight saponins were all very low, indicating a relatively low oral bioavailability. All these results provide support for further clinical studies.

Identification of a novel BACE1 inhibitor, timosaponin A-III, for treatment of Alzheimer's disease by a cell extraction and chemogenomics target knowledgebase-guided method.

BACKGROUND: Rhizoma Anemarrhenae (RA) has been conventionally used for treatment of Alzheimer's disease (AD) in Traditional Chinese Medicine, and thus, the active components from RA can be screened. PURPOSE: This research aimed to identify the active components of RA and their targets and further clarify the molecular mechanisms underlying its anti-AD activity. METHODS: First, the potential active compounds from RA were screened by neurocyte extraction and micro-dialysis methods. Second, the potential targets were predicted by a chemogenomics target knowledgebase and further explored by surface plasmon resonance and enzyme activity assays. Third, the pharmacological effects were evaluated by employing APP/PS1 transgenic mice and SH-SY5Y-APP cells. ELISAs and Western blot analyses were used to evaluate the expression of key molecules in the amyloidogenic and NMDAR/ERK pathways. RESULTS: Timosaponin A-III (TA-III) was screened and identified as a potential active component for the anti-AD activity, and BACE1 was proven to be a potential high-affinity target. Enzyme kinetic analysis showed that TA-III had strong noncompetitive inhibitory activity against BACE1. The in vitro and in vivo assays indicated that TA-III had pharmacological effects through improving memory impairment, reducing Aß aggregation via the amyloidogenic pathway and preventing neuronal impairment through downregulating the NMDAR/ERK signaling pathway. CONCLUSION: TA-III targets BACE1 to reduce Aß aggregation through down-regulating the NMDAR/ERK pathway for treating AD.

The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer.

Pancreatic cancer (PC) is a malignant tumor with a poor prognosis and high mortality. However, the biological role of miR-548t-5p in PC has not been reported. In this study, we found that miR-548t-5p expression was significantly decreased in PC tissues compared with adjacent tissues, and that low miR-548t-5p expression was associated with malignant PC behavior. In addition, high miR-548t-5p expression inhibited the proliferation, migration, and invasion of PC cell lines. Regarding the molecular mechanism, the luciferase reporter gene, chromatin immunoprecipitation (ChIP), and functional recovery assays revealed that YY1 binds to the miR-548t-5p promoter and positively regulates the expression and function of miR-548t-5p. miR-548t-5p also directly regulates CXCL11 to inhibit its expression. A high level of CXCL11 was associated with worse Tumor Node Metastasis (TNM) staging in patients with PC, enhancing proliferation and metastasis in PC cells. Our study shows that the YY1/miR-548t-5p/CXCL11 axis plays an important role in PC and provides a new potential candidate for the treatment of PC.

Comprehensive understanding of magnetic hyperthermia for improving antitumor therapeutic efficacy.

Magnetic hyperthermia (MH) has been introduced clinically as an alternative approach for the focal treatment of tumors. MH utilizes the heat generated by the magnetic nanoparticles (MNPs) when subjected to an alternating magnetic field (AMF). It has become an important topic in the nanomedical field due to their multitudes of advantages towards effective antitumor therapy such as high biosafety, deep tissue penetration, and targeted selective tumor killing. However, in order for MH to progress and to realize its paramount potential as an alternative choice for cancer treatment, tremendous challenges have to be overcome. Thus, the efficiency of MH therapy needs enhancement. In its recent 60-year of history, the field of MH has focused primarily on heating using MNPs for therapeutic applications. Increasing the thermal conversion efficiency of MNPs is the fundamental strategy for improving therapeutic efficacy. Recently, emerging experimental evidence indicates that MNPs-MH produces nano-scale heat effects without macroscopic temperature rise. A deep understanding of the effect of this localized induction heat for the destruction of subcellular/cellular structures further supports the efficacy of MH in improving therapeutic therapy. In this review, the currently available strategies for improving the antitumor therapeutic efficacy of MNPs-MH will be discussed. Firstly, the recent advancements in engineering MNP size, composition, shape, and surface to significantly improve their energy dissipation rates will be explored. Secondly, the latest studies depicting the effect of local induction heat for selectively disrupting cells/intracellular structures will be examined. Thirdly, strategies to enhance the therapeutics by combining MH therapy with chemotherapy, radiotherapy, immunotherapy, photothermal/photodynamic therapy (PDT), and gene therapy will be reviewed. Lastly, the prospect and significant challenges in MH-based antitumor therapy will be discussed. This review is to provide a comprehensive understanding of MH for improving antitumor therapeutic efficacy, which would be of utmost benefit towards guiding the users and for the future development of MNPs-MH towards successful application in medicine.

Difference in microbial community and taste compounds between Mucor-type and Aspergillus-type Douchi during koji-making.

Douchi has attracted people's attention because of its unique taste and rich health function. The microbes participated in the koji-making process contribute to taste compounds of Douchi. However, the majority of studies on Douchi focused on their functional components and the microbial community in single type of Douchi during koji-making so far. In the present study, the taste components of Mucor-type and Aspergillus-type Douchi were measured initially and the results showed that the amino acid and organic acid levels as well as the percentage of unsaturated fatty acids in Mucor-type Douchi were significantly higher than those in Aspergillus-type. The investigation of the microbial composition in two types of Douchi showed that Aspergillus, Candida, Meyerozyma and Lecanicillium were shared by >50% of samples during koji-making. Comparison of the microbial community between the two types of Douchi revealed that Meyerozyma and Lecanicillium were the main microbial community with significant difference during the initial stage of koji-making, while Candida was significantly different during the later stage of koji-making. When supplemented with Meyerozyma and Candida in Aspergillus-type Douchi, the level of all amino acid and organic acids as well as the percentage of unsaturated fatty acid was significant improved, which further validated the importance roles of the two microorganisms in enhancing the taste components of Douchi during koji-making. The results provide useful information on optimizing the microbial community structure of Douchi during the process of koji-making and improving the product quality.

Self-assembly of graphene oxide/PEDOT:PSS nanocomposite as a novel adsorbent for uranium immobilization from wastewater.

In recent years, water pollution caused by radionuclides has become a rising concern, among which uranium is a representative class of actinide element. Since hexavalent uranium, i.e. U(VI), is biologically hazardous with high migration, it's essential to develop efficient adsorbents to minimize the impact on the environment. Towards this end, we have synthesized a novel material (GO/PEDOT:PSS) by direct assembling graphene oxide (GO) and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) through a facile ball milling method, which shows impressing performance for the immobilization of U(VI). On the basis of the batch experiments, GO/PEDOT:PSS exhibits ionic strength-independent sorption edges and temperature-promoted sorption isotherms, revealing an inner-sphere complexation with endothermic nature. The sorption kinetics can be illustrated by the pseudo-second-order model, yielding a rate constant of 1.09. × 10-2 g mg-1∙min-1, while the sorption isotherms are in coincidence with the Langmuir model, according to which the maximum sorption capacity is measured to be 384.51 mg g-1 at pH 4.5 under 298 K, indicating a monolayer sorption mechanism. In the light of the FT-IR and XPS investigations, the surface carboxyl/sulfonate group is responsible to the chelation of U(VI), indicating that the enhanced sorption capacity may be ascribed to the PSS moiety. These findings can greatly contribute to the design strategy for developing highly efficient adsorbents in the field of radioactive wastewater treatment.

Qualitative and quantitative determination of Atractylodes rhizome using ultra-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry with data-dependent processing.

A quick and effective workflow based on ultra-performance liquid chromatography coupled with electron spray ionization and LTQ-Orbitrap mass spectrometry (UPLC-LTQ-Orbitrap MS) was established for compositional analysis and screening of the characteristic compounds of three species of Atractylodes rhizome for quality evaluation. This technique was employed to determine the seven main components in Atractylodes rhizome samples. Ultimately, 78 constituents were identified; of these, seven characteristic compounds were selected for species discrimination, comprising atractylodin (63), atractylenolide I (43), atractylenolide II (49), atractylenolide III (53), atractylon (69), methyl-atractylenolide II (54) and (4E,6E,12E)-tetradecadecatriene-8,10-diyne-1,3-diacetate (59). The seven main compounds, including six characteristic compounds, were simultaneously determined in 29 batches of Atractylodes rhizome samples. Thus, the method validation showed acceptable results. Quantitative analysis showed significantly different contents of the seven main components among the three species of Atractylodes rhizome, which indicates possible distinctions in the pharmacological effects. This established method can simultaneously provide qualitative and quantitative results for compositional characterization of Atractylodes rhizomes and for quality control.

Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines.

Aristolochic acid I (AAI) existing in plant drugs from Aristolochia species is an environmental human carcinogen associated with urothelial cancer. Although gene association network analysis demonstrated gene expression profile changes in the liver of human TP53 knock-in mice after acute AAI exposure, to date, whether AAI causes hepatic tumorigenesis is still not confirmed. Here, we show that hepatic premalignant alterations appeared in canines after a 10-day AAI oral administration (3 mg/kg/day). We observed c-Myc oncoprotein and oncofetal RNA-binding protein Lin28B overexpressions accompanied by cancer progenitor-like cell formation in the liver by AAI exposure. Meanwhile, we found that forkhead box O1 (FOXO1) was robustly phosphorylated, thereby shuttling into the cytoplasm of hepatocytes. Furthermore, utilizing microarray and qRT-PCR analysis, we confirmed that microRNA expression significantly dysregulated in the liver treated with AAI. Among them, we particularly focused on the members in let-7 miRNAs and miR-23a clusters, the downstream of c-Myc and IL6 receptor (IL6R) signaling pathway linking the premalignant alteration. Strikingly, when IL6 was added in vitro, IL6R/NF-κB signaling activation contributed to the increase of FOXO1 phosphorylation by the let-7b inhibitor. Therefore, it highlights the new insight into the interplay of the network in hepatic tumorigenesis by AAI exposure, and also suggests that anti-premalignant therapy may be crucial for preventing AAI-induced hepatocarcinogenesis.

[Effects of steaming and baking on content of alkaloids in Aconite Lateralis Radix (Fuzi)].

To study the effect of steaming and baking process on contents of alkaloids in Aconite Lateralis Radix (Fuzi), 13 alkaloids were analyzed by UPLC-MS/MS equipped with ESI ion source in MRM mode. In steaming process, the contents of diester-diterpenoid alkaloids decreased rapidly, the contents of monoester-diterpenoid alkaloids firstly increased, reached the peak at 40 min, and then deceased gradually. The contents of aconine alkaloids (mesaconine, aconine and hypaconine) increased all the time during processing, while the contents of fuziline, songorine, karacoline, salsolionl were stable or slightly decreased. In baking process, dynamic variations of alkaloids were different from that in the steaming process. Diester-diterpenoid alkaloids were degraded slightly slower than in steaming process. Monoester-diterpenoid alkaloids, aconine alkaloids and the total alkaloids had been destroyed at different degrees, their contents were significantly lower than the ones in steaming Fuzi at the same processing time. This experiment revealed the dynamic variations of alkaloids in the course of steaming and baking. Two processing methods which can both effectively remove the toxic ingredients and retain the active ingredients are simple and controllable, and are valuable for popularization and application.